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Reparto di Neuroscienze comportamentali, Dip. Biologia cellulare e Neuroscienze Istituto Superiore di Sanità, Roma

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Reparto di Neuroscienze comportamentali,

Dip. Biologia cellulare e Neuroscienze

Istituto Superiore di Sanità, Roma

Animal Welfare

Does the mouse have what it wants?

Is the mouse healthy?

Factors affecting phenotype

Genes… … and environment

Standardization

Standardization: Aims

• minimize individual differences within study populations(within-experiment variation)

maximize test sensitivity (reduction of sample size!)

• minimize differences between study populations(between-experiment variation)

maximize reproducibility of results

Ethical question:● Implications for the animals?

animal welfare

Scientific question:● Implications for the research?

scientific validity

Effects of the environment on animal phenotype: Two questions.

Stereotypic behaviour

Cage-induced abnormal behaviours: Stereotypies

Stereotypies

DefinitionRepetitive, invariantbehavioural pattern withoutobvious goal or function

CausationFrustration of essential behavioural needs

Consequences?

Polar Bear at Zürich ZooFoto: H. Hediger

StereotipieComportamenti relativamente invariati e ripetitivi, apparentemente privi di funzione nel contesto in cui vengono espressi (Mason, 1991)

“Le stereotipie possono rappresentare un chiaro sintomo di stress e una strategia di “adattamento” allo stimolo stressante…”

Lawrence A.B. and Rushen J. 1993. Stereotypic animal behaviour: Fundamentals andapplications to welfare. CAB International, pp. 212

Stereotypic behaviour

• Stereotypies develop from behavioural responses to the frustration of essential behavioural needs

• Stereotypies reflect the disruption of neural mechanisms involved in the inhibitory control of behaviour

• Stereotypies are pathological consequences of inappropriate housing conditions

• Current standard housing conditions for laboratory mice seem inappropriate

Stereotypies in humans:

Symptom for psychiatric disorderse.g. schizophrenia, autism

Symptom for lesions and disorders of specific brain regions (basal ganglia)

Stereotypic behaviour

A d u lt s

P e r ia d o le s c e n t s

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RELAZIONE TRA LIVELLI DI PLASMATICI DI CORTICOSTERONE E ESPRESSIONE DI STEREOTIPIE COMPORTAMENTALI in risposta a iniezione di anfetamina (10 mg/kg)

STUDYThe experience of stressful events in early life can turn to an increased predisposition to mood disorders at adulthood. Several data indicate in prenatally stressed rats increased anxiety and emotionality.

The capacity of a precocious environmental intervention to normalize the behavioural and immunological dysfunctions produced by a stressed pregnancy was investigated. In order to assess new therapeutic strategies, an environmental enrichment approach was used.

Pregnant rats underwent three-45 min/day sessions of prenatal restraint stress (PS) on gestation days 11 to 21, and offspring were assigned to either enriched-environment or standard living cages throughout adolescence (pnd 22-43).

Weaning

STRESS

P 21

Pregnancy Birth Adolescence

P 65E 10E 0

Non-enriched environmentEnriched environment

(2 rats per cage)

Prenatal Stress and depression: Therapeutic approach by means of environmental stimulation

Nel nostro modello (ratti sottoposti a stress prenatale, in rosso), la possibilità di interagire durante l’adolescenza con un ambiente arricchito (in verde) ha prodotto una significativa normalizzazione della risposta neuro-endocrina a uno stress acuto (vedi figura) e del repertorio comportamentale (stati d’ansia, interazioni sociali).

Ambiente arricchito

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ACUTE STRESS

PS-EC-NE

C-E

PS-NE

Gabbia standard

Environmental enrichment and social play behaviour

Environmental enrichment reverses the reduction of play behaviour induced by Prenatal Stress

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Controls PS Controls PS

Non - Enriched Enriched

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STATISTICAL RESULTS :

-GROUP **

- GROUP x COND *

- DRUG *

- GROUP x DRUG *

- COND x DRUG *

STATISTICAL RESULTS :

- GROUP x COND *

- DRUG *

- GROUP x DRUG **

- COND x DRUG **

-GROUP *

-COND **

-GROUP x COND **

-DRUG ns

-COND **

-DRUG **

-COND x DRUG **

STATISTICAL RESULTS :

- COND *

- DRUG *

- GROUP x COND *

- COND x DRUG **

- for hypothalamus: COND*

VI RINGRAZIAMO PER L’ATTENZIONE