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Neuroscience and Biobehavioral Reviews 35 (2011) 1854–1863

Contents lists available at ScienceDirect

Neuroscience and Biobehavioral Reviews

journa l homepage: www.e lsev ier .com/ locate /neubiorev

eview

ctodon degus. A useful animal model for social-affective neuroscience research:asic description of separation distress, social attachments and play

alentina Colonnelloa,b,∗, Paolo Iacobuccia,b, Thomas Fuchsc, Ruth C. Newberrya, Jaak Pankseppa

Center for the Study of Animal Well-being, Department of Veterinary & Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman,A 99164-6520, United States

Department of Psychology, University of Rome “Sapienza,” Rome 00185, ItalyBiology Department, Pennsylvania State University, State College, PA 16802, United States

r t i c l e i n f o

rticle history:eceived 17 November 2010eceived in revised form 16 March 2011ccepted 25 March 2011

eywords:

a b s t r a c t

A challenge for social-affective neuroscience programs is to identify simple and yet valid animal mod-els for studying the expression of basic social emotions and their role during different developmentalwindows, from infancy to adulthood. For example, although laboratory rats are useful for studyingjuvenile social interactions, they are not ideal for studying infant attachment bonds. Here, we eval-uate current understanding of the social behavior of Octodon degus, a diurnal precocial rodent, toelucidate the value of this species as a model for social-affective neuroscience research. After a syn-

odelttachmentDHDepressionnxietymotional developmentxternalizing and internalizing disorders

opsis of species-specific characteristics and brain susceptibility to changes of social environment, ourbehavioral findings on degu social proclivities are summarized. We then discuss why this pre-clinicalmodel provides a valuable addition to the commonly available animal models for the study of humanpsychopathology.

© 2011 Elsevier Ltd. All rights reserved.

ontents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18542. Species characteristics, social phenotypes, and ecology of degus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18553. Brain sensitivity to changes of social environment in degus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18564. Social bonds and effects of social isolation in infant degus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1856

4.1. Responses to acute social isolation stress in early infancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18574.2. Responses to chronic social isolation stress in early infancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1858

5. Peer interactions and their role on socio-emotional development in juvenile degus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18595.1. Peer interactions in juvenile degus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18595.2. Effects of deprivation of peer interactions during the play period . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18595.3. Effects of deprivation of peer interactions since early adolescence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1860

6. Methodological considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18607. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1861

Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1861References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

∗ Corresponding author at: Department of Veterinary & Comparative Anatomy,harmacology and Physiology, Washington State University, Pullman, WA 99164-520, United States.

E-mail addresses: vcolonnello@vetmed.wsu.edu, valentina.colonnello@gmail.om (V. Colonnello), iacobucci@vetmed.wsu.edu (P. Iacobucci), tfuchs@pitt.eduT. Fuchs), rnewberry@wsu.edu (R.C. Newberry), jpanksepp@vetmed.wsu.eduJ. Panksepp).

149-7634/$ – see front matter © 2011 Elsevier Ltd. All rights reserved.oi:10.1016/j.neubiorev.2011.03.014

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1. Introduction

The distress response of an isolated infant, the rough-and-tumble play between juveniles, and the prompt care behavior

directed towards a newborn are clear expressions of basic emo-tions rooted in subcortical neural circuits found across mammalianspecies (see MacLean, 1985, 1990; Panksepp, 1998, 1982, 2005,

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or extensive reviews). However, in the few mammalian speciesommonly used as pre-clinical neuroscience models, such neuro-iological urges and competencies are present in varying degreesPanksepp et al., 1992; Panksepp, 2003). This variation raisesuestions about which species represent appropriate models forenerating principles of brain social organization that translate toumans.

Altricial rodents have served as valuable models for the studyf important social-affective processes, such as juvenile sociallay and adult pair bonding (Aragona and Wang, 2004; Carternd Getz, 1993; Panksepp et al., 1984; Panksepp, 1998; Pellisnd Pellis, 2007; Vanderschuren et al., 1997; and see Siviy andanksepp, in this issue). Laboratory rats and mice, especially,re commonly used in behavioral research, and the need toaximize laboratory resources has led to a progressive and exten-

ive use of these altricial rodents with compressed life span fortudying infant filial bonds. Unfortunately, these species showome limitations when used for this purpose, including relativelyeak responses to social isolation, no clear preference for their

aregiver, and debatable social-separation calls (Panksepp et al.,992; Panksepp, 2003, 2005). As a consequence, reliance on thesepecies may lead to inadvertent biases and limited generaliz-bility to humans. This was one reason for choosing dogs forarly attempts to decode the neural nature of social bonds (e.g.,anksepp et al., 1978). For instance, puppies show motor agita-ion and emit distress vocalizations (DVs) at high and sustainedates when abruptly and involuntarily separated from their care-ivers (Panksepp et al., 1978; Topál et al., 1998). In dogs, andocial primates such as rhesus monkeys (Bayart et al., 1990), infantesponses to social isolation are robust, selective, and persistent,ut extensive use of these species as laboratory subjects is imprac-ical.

In this article, we summarize our work with a new behavioralodel, the degu (Octodon degus), a diurnal and precocious rodent.

his species has a relatively compressed developmental life span,ogether with a highly evolved social organization that in someays may resemble ancestral humans (e.g., group mothering by

unts, Hrdy, 2009). Our hope was that the degu may represent aelevant and economically feasible model for the study of infantttachment bonds as well as juvenile peer interactions. We werespecially motivated to invest in characterizing the social behaviorf degus by the remarkable discoveries by Katharina Braun’s groupt the University of Magdeburg (vide infra) demonstrating brainensitivities in this species to various interesting social challengesnd variables.

After an overview of the social characteristics of O. degus asell as experimentally induced brain changes in socially isolatedegus, we present a synopsis of our behavioral work on infantnd juvenile degus, which leads us to consider this species asn attractive model for the study of social-affective bonds acrossevelopmental stages. We then consider whether the degu is aeasible animal model for the study of human psychopathologyccording to classic validity criteria. If so, known risk factors for themergence of human psychopathology should induce correspond-ng pathological changes in degu behavior (causative validity). Inddition, an optimal small-animal model should display behav-ors potentially homologous to human clinical symptoms (facealidity), and conform to theoretical models of clinical condi-ions (construct validity). Moreover, therapeutic treatments foruman psychopathology should lead to similar results in the animalodel (predictive validity) (McKinney and Bunney, 1969; Redei

t al., 2001). In short, now that brain control of social bonds

nd urges that resemble attachments in our own species hasecome of great interest to many investigators, the field is in needf more valid, yet efficient, models of socio-emotional develop-ent.

avioral Reviews 35 (2011) 1854–1863 1855

2. Species characteristics, social phenotypes, and ecology ofdegus

O. degus (the “trumpet-tailed” or “brush tailed” rat or degu) is ahystricomorph rodent endemic to the semi-arid regions of north-central Chile (Fulk, 1976). Although colony size is variable, coloniestypically comprise 4–6 adult females, 1–2 adult males, plus youngfrom the current and previous litters (Fulk, 1976; Hayes et al., 2009;Wilson, 1982). Relatedness of colony members is also variable,ranging from 0.07 to 0.48 between females in one wild population,and averaging 0.25 which is equivalent to second-order kinship(Ebensperger et al., 2004). During the daytime, the group membersroam above ground and coordinate their foraging activity by keep-ing visual contact (Ebensperger and Bozinovic, 2000; Ebenspergeret al., 2002; Quirici et al., 2008; Vasquez, 1997) and emitting audiblevocalizations (Long, 2007). They synchronize their digging activityto build complex underground burrows, which they share whennight falls, and use routinely as refuges to raise their precociousbut unweaned pups (Ebensperger et al., 2004; Fulk, 1976; Lee,2004).

Degus are polygynous, plural breeders, exhibiting synchronousbreeding in combination with communal nesting and nursing(Ebensperger et al., 2002, 2004). Adult resident males aggressivelydefend their harem from intruding males in the breeding seasonwhereas they are more tolerant at other times of year (Soto-Gamboa et al., 2005). After a gestation period of about 90 days,colony females typically give birth to litters of 4–8 pups (range 1–12pups). Mothers contribute to the rearing of all pups in the commu-nal nest (Ebensperger et al., 2007), but they provide more milk totheir own young, and those of close relatives, than to the young ofnon-relatives (Jesseau et al., 2009). Unlike most laboratory rodents,and similar to prairie voles (Carter and Getz, 1993), males also par-ticipate in rearing of the young. Although the extent of paternalinvestment remains to be well documented, laboratory observa-tions have shown that fathers huddle with the pups soon afterbirth and subsequently regulate their social interactions (Wilson,1982). Furthermore, under laboratory conditions, neither malesnor females have been observed to direct agonistic or infanticidalbehavior towards infants, even when unrelated and socially unfa-miliar (Ebensperger, 2001). Communal pup care does not appearto translate into an overall improvement in postnatal survival andgrowth of pups relative to solitary breeding (Ebensperger et al.,2007; Hayes et al., 2009), suggestive of interesting social dynamicsaffecting individual reproductive fitness within colonies.

In contrast to altricial rodents, degus are born with open eyes,a functional auditory system, and an immediate ability to movearound the nest (Fox, 1965; Jamon, 2006; Reynolds and Wright,1979). Thus, similar to human infants, newborn degus are able toperceive acoustic and visual information from their social envi-ronment and interact in rich ways with their littermates andcolony mates soon after birth (Reynolds and Wright, 1979). This,of course, is of great benefit for studies conducted early in life,when potentially confounding prior developmental effects are rel-atively minimal. Despite their maturity at birth, degus have anextended period of infancy and adolescence, like primates, duringwhich they show close dependence on apparently well-recognizedfamily members. Although infants are able to maintain their bodytemperature autonomously and chew solid food by the sixth dayof life (Reynolds and Wright, 1979), and the time spent nursingis significantly reduced by the third week (20% on postnatal day21), weaning does not occur before the fourth to sixth postnatalweek (Pinkernelle et al., 2009; Reynolds and Wright, 1979; Weir,

1970). Degus exhibit philopatry, with offspring often remaining inthe natal colony into adulthood (Quirici et al., 2010), suggesting anextended period of social dependence in this species, unlike domes-tic rats and mice. Limited evidence suggests that dispersal decisions

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y both males and females are influenced by social competitionQuirici et al., 2010).

The interactions of degus are characterized by a rich vocalepertoire in the audible range, which contrasts with the lim-ted variety of vocalizations found in common laboratory rodentpecies. For example, mice emit no “alarm calls” during forag-ng activity (Blanchard et al., 2001) and domestic rat and mouse

others emit no vocalizations specific to nursing bouts. Further-ore, although social proximity with females (not just mothers)

nhibits DVs, infant rats and mice emit no calls specific to reunionith caregivers. By contrast, degus use a variety of vocalizations

o adjust their level of social proximity during all developmentaltages. For instance, isolated degu pups emit “whistle” DVs which,n early development, induce retrieval by adults (Fuchs et al., 2010;ong, 2007). Once reunited with their mother, degu infants emitpecific reunion calls, which are characterized by 4-kHz chirp-ng components (Iacobucci, personal observation). Lactating deguemales emit characteristic nursing calls, termed “mothering calls,”hat elicit suckling behavior and regulate nursing bouts (Braun andcheich, 1996). “Mothering calls” and “reunion calls” are reportednly in mammals with a strongly developed social organization,uch as monkeys (Kalin et al., 1995; Roush and Snowdon, 2001)nd domestic pigs (Colonnello et al., 2010; Illmann et al., 2002).egu pups exhibit clear bouts of rough-and-tumble play, which islso well developed in most domestic rats, but not domestic mice.hen degu pups playfully interact with their siblings, they emit a

ariety of vocalizations, including “warble” calls (Long, 2007) thatesemble their reunion calls, and when interactions between sib-ings become too vigorous, perhaps verging into aggression, theather squeaks “at” the pups and appears to actively separate themWilson, 1982). During foraging, degus emit specific alarm callsLong, 2007), and the social interactions of adults and adolescentsre accompanied by a diversity of warbling, whistling and gruntingoises (characterized by Long, 2007).

The aforementioned factors, namely maturity at birth, slowevelopment, and complex social organization, allow degu pupso engage in a variety of social interactions over a prolonged periodf development and to establish comparatively sophisticated andexible social competencies. These same factors, in combinationith a generally docile temper, relatively small size as well as ease

f breeding and maintenance, make this species a potentially idealaboratory model for social-affective behavioral and neuroscienceesearch into the nature of separation distress, social bonds, juve-ile play and other aspects of prosociality.

. Brain sensitivity to changes of social environment inegus

Over the last two decades, significant progress has been maden characterizing brain changes that occur in infant and adoles-ent degus in response to social isolation stress. A series of studiesonducted by Katharina Braun and colleagues demonstrated thatocial deprivation during the first weeks of life induces a host ofeurophysiological and neuroanatomical changes at cortical andubcortical levels in the brains of young degus. The deprivationrocedure consisted of repeated episodes of isolation from the fam-

ly unit during the first three postnatal weeks followed by earlyeaning and individual housing at postnatal day (PND) 21. At PND

5, deprived animals showed altered balance between serotonin-rgic and dopaminergic innervation in several subregions of theedial prefrontal cortex. In particular, deprived animals showed

igher synaptic density in the infralimbic cortex (Ovtscharoff andraun, 2001), altered number and density of tyrosine hydroxylase

mmunoreactive neurons (Braun et al., 2000; Poeggel et al., 2003),nd a reduced number of NADPH-diaphorase-containing neurons

avioral Reviews 35 (2011) 1854–1863

in the limbic system (Poeggel et al., 1999) compared to sociallyhoused, unhandled degus. Other studies controlling for handlingmanipulations confirmed these earlier findings and also showedthat early social isolation is associated with altered serotoninergictransmission (Jezierski et al., 2006) and altered spine densities inseveral regions of the limbic system (Helmeke et al., 2001). Similaralterations of emotional brain circuits have been found in humansgrowing up in adverse environments.

Interestingly, humans show a certain degree of resilience andbrain plasticity when facing adverse life events (Cicchetti et al.,2007; Glaser, 2000; Kaufman et al., 2004).

Some degree of resilience has also been demonstrated in degus.Two-week-old degus exposed to brief daily social isolation fromPND 8 to 10 showed an upregulation of glutamate (NMDA),dopamine (D1), and serotonin (5HT1A) receptor density in severalregions of the limbic system. However, exposure to the playbackof mothering calls emitted by an unfamiliar female counteractedthese brain changes, especially in males (Ziabreva et al., 2000,2003). This sex difference may mean that females are more depen-dent on full social contact for affective homeostasis.

Moreover, repeated social separations from PND 1 to 21 induceda decreased density of calbindin immunoreactive interneurons inthe anterior cingulate and precentral medial subregions of themedial prefrontal cortex in PND 45 degus. However, exposure to anensuing period of full socialization without handling stress partiallymitigated the effects of the previous stressful experience (Helmekeet al., 2008).

In sum, many isolation-induced alterations are evident in com-ponents of the limbic and monoamine neurotransmitter systems,which are known to be involved in human emotionality. Further-more, some of these brain alterations resemble those associatedwith mood and anxiety disorders. While the vulnerability of thedegu brain to changes in the early social environment is receiv-ing significant attention, evidence that early isolation translatesinto changes in social behavior, in the short or long term, is scarce.Therefore, we have devoted effort to the behavioral characteriza-tion and validation of this animal model.

4. Social bonds and effects of social isolation in infant degus

Our first aim was to understand whether the degu representsa useful model for the study of human infant attachment bonds.According to classical attachment theory, during episodes of invol-untary social isolation, human infants show a typical “protest”response, accompanied by emotional distress and seeking of com-forting reunions with a caregiver. Initially, infant behaviors aredirected towards anyone in the surrounding area but, once theattachment bond is established, attachment behaviors becomespecifically directed towards the caregiver. Infant vocal and motorefforts are aimed at alleviating distress and reinstating a positiveaffective state through restitution of the social reward experiencedduring physical closeness to the caregiver. In these efforts, infantsadjust their attachment behaviors in flexible ways according toenvironmental conditions, caregiver availability, and in anticipa-tion of a forthcoming reunion (Bowlby, 1969; Cassidy, 1999). Theseattachment behaviors lay the foundation for the emergence of a fil-ial attachment bond, which is distinguishable from other forms ofaffectional bonds by its persistence and selectivity for the caregiver(Cassidy, 1999).

When the attachment bond is well established, its disruptionhas long-lasting detrimental consequences for an infant’s socio-

emotional development. After prolonged separation, the infantprotest response ceases and gives way to a continuing depression-like “despair” response (Bowlby, 1969; Harlow and Zimmermann,1959; Kaufman and Rosenblum, 1967; Spitz, 1946), a model for

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Fig. 1. Mean ± SE % of DVs emitted by infant degus during the two isolation sessionsof a maternal potentiation test. Social contact restores the separation response in apotentiation paradigm. When degu pups were either placed into an empty chamberor into one that contained bedding from their home cage between two consecutiveisolations, the number of separation calls declined significantly from the first tothe second isolation (non-social conditions, pooled data). In contrast, social contact

V. Colonnello et al. / Neuroscience and B

epressive disorders that is supported by considerable evidenceWatt and Panksepp, 2009).

Within this framework, we characterized the flexibility andersistence of “protest” responses in infant degus to abrupt briefeparations at varying developmental ages. The seeking of prox-mity to, and selective preference for, the caregiver were alsotudied during acute social isolation stress. The consequences ofrolonged, chronic social isolation for infant degu socio-emotionalevelopment were investigated by limiting or eliminating social

nteractions after the parent–infant bond was expected to be firmlystablished.

.1. Responses to acute social isolation stress in early infancy

Our first observations focused on the developmental time coursef infant degu DVs during acute isolation episodes, as an indicatorf the strength of filial attachment. Thirty-eight pups from 6 littersere observed weekly during brief, 15-min periods of social iso-

ation, repeated over the first seven weeks of life. We detected arogressive decline of the separation response with age, as indi-ated by a significant reduction in the number of DVs emitteduring isolations, from an initial rate of 354 ± 89 DVs/15 min tolmost zero by the third postnatal week (Fuchs et al., in prepa-ation). Since these degus were tested repeatedly, habituation tohe test environment likely contributed to the observed decrease.ndeed, as found in a subsequent experiment controlling for pos-ible habituation effects (Colonnello et al., in press), young degusmitted 72 ± 6 DVs when isolated for 30 min for the first time atND 21. Nevertheless, littermates tested for the first time at PND1 emitted fewer DVs, indicating that a decline in DVs occurredith age in the absence of habituation (Colonnello et al., in press).

Young degus also showed flexibility in their protest response.e found that the number of DVs was higher in 3-week-old infant

egus isolated and tested for 30 min in a setting consisting ofestricted (“fenceline”) interactions with the family group throughwire-mesh grid than in control degus isolated and tested without

ocial stimuli behind the grid (328 ± 20 vs 72 ± 6.2 DVs) (Colonnellot al., in press). This finding is reminiscent of the observation byraun et al. (2003) that 8-day-old degus isolated in an unfamiliarnvironment vocalized more when exposed to playback of famil-ar sounds (i.e., “mothering calls” emitted by a lactating degu) than

hen in complete isolation.Furthermore, we found that restricted visual and acoustic con-

act with the family reestablished the isolation response at laterevelopmental time points (Colonnello et al., in press). In fact, insimilar setting, some degus emitted DVs as late as PND 56, welleyond the weaning age (Fuchs, personal observation).

Thus, although DVs declined with age, they were present for sev-ral postnatal weeks, indicating persistence of the protest responseo separation throughout developmental ages when the preco-ial pups are known to leave the nest and might get separatedrom the group. In contrast, infant rats and mice stop emittingVs around the time when they are motorically mature enough

o get lost on their own (Geyer, 1981). Furthermore, degu infantsolicited family group attention by modulating their DVs accordingo the accessibility of social partners, showing flexible separationesponses resembling typical human “goal-corrected” attachmentehaviors (Bowlby, 1969). A similar increase of DVs in response tounavailable” caretakers characterizes most well-bonded species.or example, human infants emit “negative vocalizations” duringnteractions with an unresponsive mother, such as during a Still-ace test (Legerstee and Markova, 2007; Tronick et al., 1978), and

hesus monkeys, squirrel monkeys and domestic pigs emit moreVs when exposed to an inaccessible mother placed behind a grid

han in full isolation (Bayart et al., 1990; Iacobucci et al., 2008;iener et al., 1990).

with either the mother or an unfamiliar female resulted in an increase in the averagenumber of separation calls relative to the non social setting during isolation 2 (socialconditions, pooled data) (adapted from Fuchs et al., 2010). *p < 0.05.

We also investigated the specificity of the mother–infant bond.As aforementioned, degus nest and nurse communally, a fact rarelyaddressed in studies underscoring similarities between humansand rodents. It has been demonstrated that adult female degus candiscriminate between their own pups and those of other colonyfemales based on odor cues (Jesseau et al., 2008). Although lactat-ing degus will retrieve and nurse unrelated young (Ebenspergeret al., 2006), they apparently use information about pup identityin the provisioning of milk (Jesseau et al., 2009). To find out ifinfant degus can also recognize their biological mother, we testedthem in a maternal potentiation paradigm. The term “potentia-tion” refers to an increase in the number of DVs observed fromone isolation session to the next when pups are allowed briefcontact with their mother between isolations. Although, in labo-ratory rats, such potentiation was initially assumed to be specificfor the mother it can also be found following exposure to othersocial partners (see Shair, 2007 for a full description). We tested5-day-old degus by exposing them to either non-social (nest odoror “no odor” control) or social (mother or unfamiliar non lactatingfemale) conditions between isolations. During the second isola-tion, controls and infants previously exposed to nest odor showeda marked decline in their separation response, while infants previ-ously exposed to social partners emitted DVs at rates comparable totheir first isolation (Fuchs et al., 2010, Fig. 1). Comparable “persis-tence” has been found in other precocious social species (Colonnelloet al., 2010; Hennessy et al., 2006). However, the increased persis-tence of the separation response in social conditions was observedat similar levels in both the mother and stranger groups. Similar toaltricial rodent species and unlike guinea pigs, infant degus, there-fore, did not differentiate between their mother and a stranger inthis test. It remains to be determined whether this lack of behav-ioral discrimination was observed because attachment bonds werenot fully established in 5-day-old degus or if the maternal potenti-ation paradigm is not suitable to detect infant-mother recognitionin this species. This was noted previously in domestic pigs, in whichreunion responses were better indicators of maternal recognition(Colonnello et al., 2010).

White et al. (1982) also reported that infant degus could notdiscriminate between mothers and lactating strangers in a choice

paradigm, yet they found a seemingly counterintuitive preferencefor the stranger that implies discrimination. Observations of pupsof different ages (from PND 10 to 21) were pooled in this study, witha possible confounding effect of age. After further testing we found

1 Biobehavioral Reviews 35 (2011) 1854–1863

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Fig. 2. Mean ± SE % preference of young degu pups (n = 16 per group, 8 males and 8females) for their mother vs an unfamiliar female during the first social choice testafter 10 days of continuous isolation (ISOLATED), isolation plus “fenceline” family

858 V. Colonnello et al. / Neuroscience and

hat, when offered a choice between their mother and an unfa-iliar lactating female, 15-day-old pups did prefer their mother.owever, this preference was demonstrated only when pups were

ested with their siblings, but not when they were tested individ-ally. The individually tested degus were still able to discriminateetween nest odors, and emitted more DVs in contact with theirome cage bedding (Fuchs et al., 2010), a finding reminiscent ofhe “restricted reunion” effect described above (Bayart et al., 1990;olonnello et al., in press; Iacobucci et al., 2008; Wiener et al.,990). In summary, infant degus show flexibility in their separationesponses at early developmental ages and in different experimen-al settings. In addition, infant degus have the capacity to recognizeheir biological mother at roughly two weeks of age, althoughhey do not demonstrate this ability in every test setting. Likewise,egu mothers are able to recognize their own offspring. Additionalesearch will need to address the developmental time course, speci-city and persistence of social attachments between individuals ofarying age and relatedness in complex degu colonies.

.2. Responses to chronic social isolation stress in early infancy

In humans, as in other mammals, proximity seeking to the care-iver presumably serves as a modulator of infant emotional statend the caretaker’s responses influence the infant’s perception ofotential dangers in the surrounding environment (Hay, 1980). As aesult, quality and quantity of parent–infant interactions influencen infant’s emotional balance between the need for proximity to thearegiver and the exploration of novel stimuli in the environmentAinsworth and Bell, 1970; Ainsworth et al., 1978). Thus, duringnteractions with primary attachment figures, infants of stronglyonded species exhibit specific attachment patterns (Ainswortht al., 1978; Suomi, 1999; Topál et al., 1998). Infants reared inositive and responsive social environments are more inclined toevelop a “secure” attachment pattern and utilize the caregiver as“secure base” for the exploration of social and environmental

timuli. By contrast, infants who have experienced certain formsf physical and emotional neglect show a stronger risk of devel-ping an “insecure” attachment pattern, which is associated withltered levels of proximity seeking to the caregiver and exploratoryctivity (Ainsworth and Bell, 1970; Suomi, 1999).

Accordingly, we investigated the long-term impact of differ-nt levels of social contact on degu socio-emotional development.iven that infant degus exposed to restricted interactions withocial partners show potentiated protest responses when unableo obtain contact, perhaps reflecting a “frustration” response aris-ng from not being able to achieve a full reunion, we incorporatedrestricted contact condition in our study. To our knowledge, the

mpact of repeated exposure to such conditions on infant devel-pment has not previously been investigated in animal models ofocial attachment.

Differences in approach to novel social and environmental stim-li were observed in three groups of degus reared with varyingegrees of social contact. At 3 weeks of age, after the mother–infantttachment bond was presumably well established, degu pups werelaced in continuous isolation (ISOLATED group), kept in isolation

nterrupted by daily 30-min restricted interactions with their fam-ly members (mother and littermates) through a wire-mesh gridRESTRICTED group), or housed socially with their family membersSOCIAL group). After 10 days, all subjects were observed during aingle 10-min exposure to a novel environment, and daily for 5 daysuring a 10-min social choice test (mother vs unfamiliar female).

We found that, during the first 3 days of the 10-day treatment

eriod, the RESTRICTED degus showed an elevated vocal protestesponse (DVs) and sustained proximity seeking towards their fam-ly during the entire 30-min restricted access period. By contrast,he ISOLATED degus exhibited markedly decreased DVs and motor

contact for 30-min daily (RESTRICTED) or continuous free access to family members(SOCIAL). Data are presented in 5 blocks of 2 min each (adapted from Colonnelloet al., in press). *p < 0.05.

activity after 2 days of treatment. These animals settled in a pas-sive crouching posture resembling the depression-like symptomsobserved in socially deprived human babies and non-human pri-mates (Kaufman and Rosenblum, 1967; Spitz, 1946). Given that themarked decrease of exploration in the ISOLATED degus could sim-ply reflect habituation to the isolation environment, further studiesare needed to assess whether the observed crouching posture isaccompanied by other depression-like responses in degus.

After the 10-day treatment period, when the animals wereplaced individually in a novel environment, ISOLATED animalsshowed increased locomotor activity and defecation, possiblyreflecting escape attempts and thus a sustained increase in anx-iety compared to the other groups (Colonnello et al., in press).Differences among rearing conditions were also evident duringthe social choice tests. In particular, during the first choice test,degus in the SOCIAL group spent more time close to their motheronly during the initial minutes of the test, resembling a “secureattachment” pattern, while those in the RESTRICTED group showedpersistent proximity seeking to their mother throughout the entiretest session, resembling human “insecure attachment”. Finally, theISOLATED animals spent a comparable amount of time close to theirmother and the unfamiliar female, showing no social preference(Fig. 2; Colonnello et al., in press).

In other words, different rearing conditions were associatedwith different behavioral profiles. Both groups reared under iso-lation conditions showed forms of anxiety compared to animalsreared in continuous, full contact with their family members.However, while degus in the ISOLATED group were neophobictowards the novel environment, perhaps RESTRICTED animals wereneophobic towards the unfamiliar female. No rearing condition dif-ferences were evident after the first social test day, presumablydue to familiarization with the environment and unfamiliar female.Given that the pups were reared only by their mother and not incommunal nests with older siblings and other adults, it would beof interest to take into account this aspect of the species-specificbiology of degus in future studies.

Based on the above observations, the degu exhibits considerablepromise as a valid animal model for the study of early infant attach-ments. Degu infants showed persistent and flexible attachmentbehaviors during social separations. Moreover, infants discrimi-nated and preferred their mother over unfamiliar lactating females,as monitored by choice tests (Colonnello et al., in press; Fuchs et al.,2010). Infants remained in proximity to their mother at develop-

mental ages when they could eat solid food and their need formaternal milk was greatly reduced, suggesting that their seek-ing of proximity to the caregiver was not driven by a need fornourishment per se but, rather, a direct expression of their social

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eeds. Indeed, growth was not compromised in early-weanedegus (Becker et al., 2007) or those placed in prolonged isolation atND 21 (Colonnello et al., in press). Furthermore, our finding thatsychological vulnerability was not limited to continuous social

solation but was also observed at varying degrees of isolationncourages the further study of the degu as a model for humanttachments. Prima facie, the distinct behavioral profiles observedn isolated degus resemble human “secure” and “insecure” attach-

ent patterns. It is noteworthy that just as in our own species,n which young children try to maintain a close bond even witheglectful caregivers (Cicchetti and Toth, 1995), young RESTRICTEDegus tried to reach their social group even after several days ofhwarted access, which was presumably a very unsatisfying statef affairs. Thus, the urge to maintain a social bond in degus is strongnd enduring, regardless of the quality of the social interactions.

Future studies may elucidate the specific factors influencing theormation and persistence of parent–infant bonding in this species.n particular, we need to determine the role of “mothering calls” andnfant “reunion calls” in facilitating parent–infant recognition andonding. Whether such calls are modulated by social rearing con-itions is another key question that needs to be addressed. Alonghese lines, it is worth noting that in another precocial species,he domestic pig, infants modulate the number of “reunion calls”ased on the time spent away from the family group and the qual-

ty of interactions with the caregiver (Colonnello et al., 2010). Ourngoing research is currently focused on the long-term effects ofocial isolation on emotional development of degus isolated sincehe second week of life. The current pattern of results affirms thathe degu is a fine species for studying the neurobiology of attach-

ent bonds. The data also suggest that this species may be usedo model insecure attachment patterns, which is a major topic inuman attachment research, but for which no small animal modelet exists.

. Peer interactions and their role on socio-emotionalevelopment in juvenile degus

The protracted period of infancy and adolescence spent in theatal colony allows young degus to interact with siblings and non-iblings for a considerable period of time before they disperse orecome fully integrated adult colony members. Thus, we have been

nterested in investigating the characteristics of social peer inter-ctions and their role throughout development.

.1. Peer interactions in juvenile degus

Studies on peer play activity have demonstrated that, in mostocial mammals, an urge for rough-and-tumble play emerges inarly stages of life, peaks during the juvenile period, and declinest puberty (Panksepp, 1998; Pellis and Pellis, 2007). It is, thus, toe expected that social play is an “experience expectant” process

n all mammals, which helps construct and solidify the social skillseeded later in life. Considerable progress has been made in under-tanding the brain mechanisms that regulate play in juvenile ratsSiviy, in this issue). To see how well future research on play pro-esses could be pursued in another convenient laboratory species,e proceeded to characterize the expression and developmentalatterns of play in young degus. Contrast between rats and degusay be especially interesting since the former are born altricial,

nd the latter, precocious.Thanks to their well-developed sensory and motor abilities at

irth, young degus have substantive social exchanges with theiriblings from the first days of life. By the second postnatal week,egus show coordinated episodes of rough-and-tumble play, inhich they alternate their dominance-submission roles. The play-

avioral Reviews 35 (2011) 1854–1863 1859

ful behaviors observed are “dorsal contacts” (paw contact with thedorsal surface of the play partner), “riding” (the play partner ismounted from behind, then the pair starts to run forward) and“foreleg push” (both partners face each other on their hind legsand paw at each other with their forelegs, a behavior that precedesmore serious forms of fighting in adults; for an earlier account ondegu play see Wilson and Kleiman, 1974). All of these behaviorsare accompanied by “play vocalizations,” which have been char-acterized as “warbles” (Long, 2007), and closely resemble friendlyvocalizations emitted by adults (Braun and Scheich, 1997) as wellas the “mothering call” emitted by nursing females.

Play is clearly a major emotional urge in young degus. Indeed,2-week-old degus show a “play rebound” effect when reunitedfollowing 12 h of isolation (Fuchs et al., in preparation), an effectsimilar to that reported in rats (Holloway and Suter, 2004;Panksepp et al., 1984). Through focal observations of degus in theirfamily groups during the first three weeks after birth, Pinkernelleet al. (2009) reported that pups decreased their play activity in thethird week of life. By contrast, in young degus reared without theirfather and observed in the absence of adults, we found that siblingplay activity continued for the first 6 weeks of life at comparablelevels (Fuchs et al., in preparation). Possibly, the inhibitory role ofolder family members (Wilson, 1982) accounts for the differencesbetween findings. Whether play activity in degus persists for a suf-ficiently long developmental window as to promote complex socialorganization in this species awaits further investigation.

5.2. Effects of deprivation of peer interactions during the playperiod

In light of their motivation for social attachment and play, itis not surprising that deprivation of peer interactions for a pro-longed period has negative effects on young degu emotional andsocial development. To evaluate the potential utility of this model,we observed the developmental trajectories of young degus thatwere chronically isolated (CHRONIC ISOLATION group), isolated butallowed to interact freely with a sibling for 1 h daily (PARTIAL ISO-LATION group), or reared with continuous free access to a sibling(SOCIAL group) starting on PND 25 (Colonnello et al., 2011).

After two weeks, chronically isolated degus, but not thoseallowed 1 h of interaction daily, showed maturational delay of fearresponses, failing to show freezing behavior in response to unex-pected loud noises. After two more weeks of isolation, chronicallyisolated animals exhibited impaired fear responses and increasedrisk-taking behaviors during the exploration of novel environ-ments, as measured during open field and novelty tests. Thechronic isolation stress also promoted the consumption of palat-able sucrose solution, as monitored in a sucrose preference testin which the alternative was plain water. Other effects of socialisolation were observed in the social domain: both isolated andpartially isolated animals emitted fewer warble vocalizations dur-ing interactions with unfamiliar social partners than animals rearedsocially. A “diet” of intermittent social peer interactions (reunionsfor 1 h each day) attenuated the effects of isolation and aided thedevelopment of fear and inhibitory responses. However, only thecontinuous availability of peers promoted a functional develop-ment of social abilities (Table 1; Colonnello et al., 2011), suggestinga dissociation between the maturation of fear-related responsesand social skills in this species.

In sum, during the juvenile period, the deprivation of social peerinteractions impairs the development of adaptive fear responses,and qualitative aspects of social behavior, in degus. In humans,

the regulation of emotional abilities typically develops along withthe maturation of frontal lobe inhibitory functions. However, chil-dren with externalizing problems are more likely to show impairedfrontal lobe regulatory functions, difficulty in regulating their emo-

1860 V. Colonnello et al. / Neuroscience and Biobehavioral Reviews 35 (2011) 1854–1863

Table 1Mean ± SE % sucrose preference, and frequencies of central crosses in an Open Field test (n/5 min), entries to a novel area in a Novelty test (n/20 min), and warble vocalizationsduring a Sociability test (n/20 min). Data refer to the responses of 52-day-old degus (n = 16 per group, 8 males, 8 females) tested after 4 weeks of chronic isolation (CHRONICISOLATION), isolation in conjunction with free access to a sibling for 1 h daily (PARTIAL ISOLATION), or continuous free access to a sibling (SOCIAL) (adapted from Colonnelloet al., 2011).

Rearing condition Test and relative response

Sucrose% Sucrose preference

Open fieldFreq. central crosses

NoveltyFreq. entries novel area

SociabilityFreq. approach vocalizations

CHRONIC ISOLATION 98 ± 1* 9 ± 1* 20 ± 2* 12 ± 2PARTIAL ISOLATION 83 ± 4 6 ± 1 10 ± 2 9 ± 3

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ions, and impaired social communication skills. They show alteredeward processing, deficient inhibition, and impaired performancen task-set shifting (Romer et al., 2009; Rubia et al., 2007; Sonuga-arke et al., 2008; Tsujimoto, 2008) as found, in part, in ourhronically isolated degus. It is noteworthy that, contrary to ratodels of depression, in which such stressors generally decrease

ucrose consumption, isolated degus exhibited elevated consump-ion.

In children, friendly peer exchanges generally promote socialevelopment and counteract the emergence of externalizingehaviors (Witvliet et al., 2009). Likewise, positive peer interac-ions arising from modest social play opportunities (i.e., wheneunited for 1 h daily) appeared to counteract the kinds of behav-oral deficits produced by isolation in degus. Thus, our resultsupport the hypothesis that availability of playful peer interac-ions may facilitate the development of emotional regulation andocial abilities (Gordon et al., 2003; Panksepp et al., 2003; Panksepp,007).

These behavioral findings are propaedeutic for further valida-ion of this animal model of human externalizing disorders duringarly childhood and suggest other inquiries about protective fac-ors for emotional and behavioral disorders that are common inumans. Future research should focus on the ontogeny of impulseontrol problems and how peer interactions aid emotional reg-lation, as developmentally evaluated in degus reared in moreaturalistic environments (e.g., with both parents, older siblings,nd non-siblings). Evaluation of impulsivity, in its various forms ofisinhibition (i.e., inability to inhibit ongoing response) includingdelay aversion” in children (i.e., marked preference for immediateewards over delayed, but greater, rewards), could be performedn degus deprived of peer social play at different developmentaltages. Such impulsivity seems to be a core behavior in external-zing disorders and may be evident during approach to variousnvironmental stimuli as well as during social interactions.

In addition, overactivity, another main feature found in exter-alizing disorders, should be systematically investigated in both

amiliar and unfamiliar environments. For instance, our chroni-ally isolated juvenile degus exhibited no overactivity (measured asverall motor locomotor activity) during the open field and noveltyests. In other words, the isolated group showed an increased pref-rence for entering the center of the open field without any overallncreased motor or locomotor activity. However, overactive chil-ren may show restlessness and overactivity selectively in familiarontexts (Sagvolden et al., 1998).

.3. Effects of deprivation of peer interactions since earlydolescence

We have found that social isolation since early adolescence

nduces an emotional profile resembling some symptoms of humannxiety disorders, indicating that peer interactions serve an impor-ant role beyond the play period in degus. We contrasted behavioralrofiles of 8 female degus housed socially and 8 females that were

9 ± 2 39 ± 11*

isolate-housed at PND 45. When tested four months later, theisolated degus showed altered responses in emotional tests com-pared to socially housed degus (Colonnello et al., submitted forpublication). Specifically, the isolated females again expressed anincreased hedonic response in a sucrose preference test, increasedanxiety during an open field test, and an initial freezing responsein conjunction with diminished exploration when exposed to anovel environment. Of course, no one has demonstrated reducedintake of sweets in depressed humans. Instead, the response tostress is often associated with increased intake of sweets in chil-dren (Mennella et al., 2010) as well as in adults (Oliver et al.,2000). Thus, we should leave open which is the more human-characteristic response and proceed with a more critical and carefulconceptualization of human anhedonic responses to develop valu-able preclinical models of depression.

Intriguingly, the isolated degus also showed a freezing responsewhen exposed to a “lost” pup (outside the nest) in a familiar envi-ronment, and a longer latency to approach the pup than sociallyhoused individuals, suggestive of neophobia. Additionally or alter-natively, perhaps the isolated degus perceived the infant emotionalstate as aversive, and were unable to regulate their emotions andexhibit prosocial behaviors. Given that, under natural conditions,adults participate in alloparenting of younger siblings and non-siblings, and pup survival may be dependent on the cooperationand prosocial behavior of all group members, the above-noted defi-ciency in responsiveness to pups highlights how living in socialisolation could impair social fitness in degus.

Similarly, whereas human parents and other adults naturallydirect caretaking behavior towards lost infants, individuals withhigh anxiety levels and experiences of social exclusion show alteredresponsiveness to infant signals (Burchinal et al., 1996; Glockeret al., 2009; Kringelbach et al., 2008; Nicol-Harper et al., 2007).Social isolation and unsatisfying peer relationships during adoles-cence also increase anxiety, especially when confronted by novelty(Chartier et al., 1998), which may promote depression later in life(Hankin et al., 2007; Larson et al., 1990). A long tradition of researchhas focused on effects of early maternal care on future parent-ing ability of offspring. However, deficient relationships with theinfant, such as in post-partum depression, can also be found inwomen who have experienced positive interactions with parentsduring childhood, but lack social support during later stages of life(Robertson et al., 2004). To assess the validity of degus for mod-eling these processes, future studies on degus should investigatewhether high anxiety levels due to post-weaning social isolationpersist after re-socialization experiences and parenthood.

6. Methodological considerations

Some methodological considerations should be taken intoaccount when using degus in laboratory settings. The first concernsthe long gestation period (Lee, 2004) which, on one hand, may facil-itate the study of prenatal development and emotional changes in

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regnant females during the different gestational phases but, on thether hand, adds to the cost of colony maintenance and prolongsntergenerational studies. Secondly, due to strong social prefer-nces and aversions, adult degus have to be monitored closelyor potentially fatal fighting when first introduced. Thirdly, whendults are kept in male–female pairs, it may be necessary to limithe number of new litters produced. In our studies, we separatedhe male from the female before the pups were born to preventostpartum pregnancies, but paternal deprivation early in life could

nfluence the social emotional development of the young.In this context, it is noteworthy that in our studies, infant male

egus showed stronger protest responses to isolation than infantemales (Colonnello et al., in press). However, we found an over-ll lack of sex differences in juvenile degus observed during thelay period, regardless of their rearing condition (Colonnello et al.,011). Whether this lack of sex difference was influenced by thebsence of the father is unknown. Several studies suggest that theather may play a crucial role in the early neurodevelopment of off-pring (Helmeke et al., 2009; Pinkernelle et al., 2009), but not inerinatal survival rates (Ebensperger et al., 2010). Thus, the behav-

oral characterization of possible sex differences in vulnerabilitynd resilience of degus reared in different family structures woulde relevant for further validation of this promising animal model.hese studies would be especially relevant considering that, inumans, sex-related differences in the onset and manifestation ofmotional disorders emerge in early childhood (Dekker et al., 2007;ahn-Waxler et al., 2008).

As for other animal models, behavioral assessment should takepecies-specific characteristics into account. Under natural condi-ions, degus run from one burrow to another and travel across openreas during the day (Ebensperger and Bozinovic, 2000). Therefore,tudies including the open field test and other tests aimed at assess-ng fear responses should be developed using suitable protocols.or example, the use of a regular 70 cm × 70 cm × 70 cm (relativelymall) open field arena might mask behavioral differences betweensolated and socially housed young degus in classic measures ofnxiety (Braun et al., 2003; Cloutier et al., in preparation). In addi-ion, because degus are visually perceptive in the ultraviolet rangeChavez et al., 2003; Quirici et al., 2008), visual cues should be care-ully controlled according to experimental goals. Finally, particularttention should be also paid to sucrose concentrations in pref-rence tests and conditioning using palatable food due to a greatulnerability to diabetes mellitus of this species.

. Conclusions

O. degus is an animal model offering fruitful new opportu-ities for investigating the environmental and neural processesnderlying human social affectional bonds and their role in emo-ional development later in life. Degus also offer a potentiallyseful model for the study of human psychopathologies, includingDHD, depression and anxiety disorders. Social deprivation, which

s a widely acknowledged risk factor for human psychopathol-gy, induces a series of species-atypical behaviors in degus. Inumans, social deprivation has distinct age-specific effects. Like-ise, in degus, a disruption of the social environment may haveifferent effects during successive developmental windows.

During infancy, chronic isolation or restricted interactions withrimary caregivers and other available social partners influenceegu social skills negatively and impair motivation to explore noveltimuli, as in human infants. During the phase of high juvenilelay, diminished availability of peer interactions increases the like-

ihood of risk-taking behaviors and alteration of reward processing,hich are behavioral alterations similar to some of the symptoms

ound in children with ADHD and other externalizing disorders.urthermore, chronic isolation during adolescence increases the

avioral Reviews 35 (2011) 1854–1863 1861

risk for emergence of atypical behaviors resembling the symptomsof human anxiety and depressive disorders. Thus, this pre-clinicalmodel seems likely to satisfy causative and face validity criteria.

Our findings so far also provide optimism that degu models ful-fill predictive validity criteria for the positive influences of earlysocial stimulation in promoting resilience to future stressors. Asdemonstrated by the fine work of Braun’s group, exposure to selectsocial stimuli can offer valuable neurodevelopmental support, atboth behavioral and neurophysiological levels, for recovering fromongoing and previous stressful experience (Ziabreva et al., 2000,2003). We note that the predictive validity of animal models istypically assessed by observing animal therapeutic responses topharmacological agents. However, we initially decided to observethe responses to a “treatment” based on repeated exposures to posi-tive social exchanges. We opted for this validation method becausewe wished to focus on a developmental period corresponding tohuman late childhood, during which pharmacological treatmentsmay not be desirable due to unknown neurodevelopmental effects.Our findings indicate that the availability of peer exchanges for justan hour a day mitigates the effects of social isolation and induces aphenotype that is more similar to socially housed animals than iso-late housed ones. Likewise, in humans, social support is consideredamong the most protective factors, exerting positive effects duringstressful negative life events (Ozbay et al., 2008; Silk et al., 2007).

The development of an ideal animal model that meets theconstruct validity criterion is particularly difficult. Human external-izing and internalizing disorders are complex and heterogeneousconditions that cannot yet be attributed to specific brain alterationsor exclusively to specific genetic susceptibility factors. However,for a promising attempt to validate this pre-clinical model, weagain turn to the findings of Braun’s group. These investigatorshave found that changes in balance of serotoninergic and dopamineinnervations in early socially isolated degus resemble the brainchanges found in humans exposed to early adverse social expe-riences (Ovtscharoff and Braun, 2001; Zehle et al., 2007).

We conclude that O. degus appears to be a suitable model foradvancing knowledge on the emergence of human psychopathol-ogy across the life span. These creatures may supplement the finework being done on adult pair bonding in prairie voles with a modelfor developmental attachment dynamics, in well controlled waysthat may not be possible with altricial species.

Acknowledgements

This research was supported by a Hope for Depression ResearchFoundation grant to J.P.

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