rat sex and strain differences in responses to stress

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Rat sex and strain differences in responses to stress Martha M. Faraday * Department of Medical and Clinical Psychology, Uniformed Services University of the Health Sciences (USUHS), 4301 Jones Bridge Road, Bethesda, MD 20814, USA Received 29 May 2001; received in revised form 28 November 2001; accepted 4 January 2002 Abstract Sensitivity to stress has been linked to the development of a variety of physical and psychological disorders. Studies to-date have focused on extreme stress phenotypes, have studied mostly male responses, have used limited dependent variables, and have included a limited number of measurement time points. The present experiment was designed to address these limitations. Feeding, body weight, open-field activ ity , acoust ic startle reflex (ASR), and prepul se inhibiti on (PPI) respon ses of adult male and female Sprague– Dawle y and Long Evans rats to daily immobilization stress (20 min/day) were evaluated for 3 weeks. Stress significantly decreased feeding and body weight of males but generall y not of femal es. Effects were greatest in Long Evans males . Stre ss decre ased 15-min activi ty levels for males on Stress Day 1, but not on other days. Stress did not affect 15-min acti vity levels of Long Evans femal es but decre ased 15-min activ ity levels of Sprague– Dawley females on every measurement day. ASR responses to stress differed based on rat strain; percent PPI responses differed based on rat strain and sex. Stress increased startle responses of Sprague–Dawley males and females but not of Long–Evans males and females. Stress reduce d PPI of Long Evans females on every measurement day but not of other groups. These finding s indicate that strain and sex of rat is impor tant to consi der in evalu ating behavior al and physio logi cal responses to stress. D 2002 Elsevier Science Inc. All rights reser ved. Keywords: Restraint stress; Sprague– Dawley rats; Long– Evans rats; Feeding; Body we ight; Open-field activity; ASR; PPI; Strain diff erences; Sex diffe rences; Individual differences 1. Introduction It is well known that stress affects physiological and be- havioral responses [1–6]. It has been recognized for more than a century that organisms within the same species can differ markedly in physiological and behavioral responses to stress [7–13]. It also is well established that sensitivity to stress is linked to the development of a variety of physical and psychological disorders [13–19]. Understanding why individuals exhibit differential responses to stress, therefore, is important to further the basic science of stress vulnerability as well as to effectively treat and prevent str ess-related illness in at-risk individuals. Gender is one maj or variable that appear s to confer  differential vulnerability to stress. Men and women differ in physiological and behavioral responses to stressors, in stress response time -courses, and in epide miol ogic patt erns of stress-related illness [5,20–29]. In humans, these differences might be explained partly by gender differences in social and cultural roles and pressures. Sex differences in sensitivity to stress, however, also have been documented in animals [30–34]. The biologic fact of gender, therefore, appears to predispose organisms to certain types of stress vulnerability. Gender does not compl etely account for stress vulner- abili ty , howev er. Indi vidua ls vary with in-gen der in stress responding as well as in susceptibility to stress-related di- sease [12,14,18,24,35 37]. In addition, an extensive animal lite ratur e has documented within-s ex vari abili ty in stres s sensitivity (i.e. strain differences), suggesting that these dif- feren ces are biologic ally and, in part icular , genot ypical ly based [8,36,38]. Rats are a valid model to understand the extent to which gender and genot ypic differen ces in stress sensitivity are biologically based rather than socially or culturally deter- mined. Study of stress sensitivity differences in rats, how- ever, has been limited in four ways. First, most of the work done in rats has focus ed on ext reme str ess phenotypes  rat strains specifical ly bred for stress sensit ivit y or stres s insensitivity on a particular dependent measure (e.g. Refs. [8,38,39]). This focus has produced a detailed picture of the 0031-9384/02/$ – see front matter D 2002 Elsevier Science Inc. All rights reserved. PII: S0031- 9384(02 )00645- 5 * Tel.: +1-301-295-9 671; fax: +1-301-295-3034. E-mail addres s: [email protected] (M.M. Faraday). Physiology & Behavior 75 (2002) 507–522

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