Short-term and long-term effects of repeated social defeat during adolescence or adulthood in female rats

Accumulating evidence suggests that adolescence represents a sensitive period during which social stressors influence adult behavior and stress reactivity. However, relatively little is known about the impact of social stress in adolescence on behaviors or stress reactivity in females. In this study, we exposed adolescent or adult female rats to the repeated social stress of defeat for seven consecutive days. Repeated defeat resulted in distinctly different behavioral repertoires during defeat in adolescent compared to adult female rats. Adolescent females exhibited more play and avoidant behaviors and adult females exhibited more active and aggressive behaviors toward the resident female. Examination of the short-term effects of social defeat using the Porsolt forced swim test (FST) indicated that adolescents, regardless of their exposure to social defeat, showed increased time immobile and decreased time swimming compared to adults. Adolescent rats exposed to defeat also exhibited increased climbing compared to their age-matched naïve counterparts. These effects dissipated with age. Interestingly, no effects of defeat were observed in adult females, however, when these females were re-assessed in the FST 30 days after the end of defeat, we observed increased swimming at the expense of climbing. Using exposure to a novel restraint to assess stress reactivity, we found that stress during adolescence and adulthood led to lower basal adrenocorticotropic hormone concentrations and that both stressed and control adolescent groups exhibited a delay in recovery in adulthood compared to stressed and control adult groups. Fos protein analysis further suggested that cortical/thalamic structures serve as potential substrates that mediate these long-term impacts of stress during adolescence. Thus, repeated social stress during adolescence produces different patterns of effects as compared with repeated social stress during adulthood.

[1]  S. Bhatnagar,et al.  Corticosterone can act at the posterior paraventricular thalamus to inhibit hypothalamic-pituitary-adrenal activity in animals that habituate to repeated stress. , 2006, Endocrinology.

[2]  Michael Rickels,et al.  Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants , 1995, Psychopharmacology.

[3]  J. Groves,et al.  Is it time to reassess the BDNF hypothesis of depression? , 2007, Molecular Psychiatry.

[4]  I. Lucki,et al.  Fluoxetine treatment induces dose dependent alterations in depression associated behavior and neural plasticity in female mice , 2010, Neuroscience Letters.

[5]  James P. Herman,et al.  Limbic system mechanisms of stress regulation: Hypothalamo-pituitary-adrenocortical axis , 2005, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[6]  S. Bhatnagar,et al.  Struggling behavior during restraint is regulated by stress experience , 2008, Behavioural Brain Research.

[7]  R. Dielenberg,et al.  Coping with defeat: acute glucocorticoid and forebrain responses to social defeat vary with defeat episode behaviour , 2009, Neuroscience.

[8]  S. Bhatnagar,et al.  Facilitation of hypothalamic–pituitary–adrenal responses to novel stress following repeated social stress using the resident/intruder paradigm , 2003, Hormones and Behavior.

[9]  R. Moos,et al.  Coping, stress, and social resources among adults with unipolar depression. , 1984, Journal of personality and social psychology.

[10]  J. Herman,et al.  Stress vulnerability during adolescent development in rats. , 2011, Endocrinology.

[11]  S. Bhatnagar,et al.  Lesions of the Posterior Paraventricular Thalamus Block Habituation of Hypothalamic‐Pituitary‐Adrenal Responses to Repeated Restraint , 2002, Journal of neuroendocrinology.

[12]  M. Meaney,et al.  The role of the medial prefrontal cortex (cingulate gyrus) in the regulation of hypothalamic-pituitary-adrenal responses to stress , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[13]  S. Bhatnagar,et al.  Social isolation in adolescence alters behaviors in the forced swim and sucrose preference tests in female but not in male rats , 2012, Physiology & Behavior.

[14]  R. Valentino,et al.  Individual differences in reactivity to social stress predict susceptibility and resilience to a depressive phenotype: role of corticotropin-releasing factor. , 2010, Endocrinology.

[15]  Paul E. Sawchenko,et al.  Regional Differentiation of the Medial Prefrontal Cortex in Regulating Adaptive Responses to Acute Emotional Stress , 2006, The Journal of Neuroscience.

[16]  K. Miczek,et al.  Escalated Aggressive Behavior: New Pharmacotherapeutic Approaches and Opportunities , 2004, Annals of the New York Academy of Sciences.

[17]  B. McEwen Early life influences on life-long patterns of behavior and health. , 2003, Mental retardation and developmental disabilities research reviews.

[18]  M. Hamon,et al.  Repeated social defeat-induced depression-like behavioral and biological alterations in rats: involvement of cholecystokinin , 2008, Molecular Psychiatry.

[19]  A. R. Foilb,et al.  The transformation of hormonal stress responses throughout puberty and adolescence. , 2011, The Journal of endocrinology.

[20]  J. Weinberg,et al.  Effects of fetal ethanol exposure on pituitary-adrenal sensitivity to secretagogues. , 2000, Alcoholism, clinical and experimental research.

[21]  K. Lambert,et al.  Coping strategies in male and female rats exposed to multiple stressors , 2003, Physiology & Behavior.

[22]  C. McCormick,et al.  Adolescent development, hypothalamic-pituitary-adrenal function, and programming of adult learning and memory , 2010, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[23]  G. Neigh,et al.  Exposure to repeated maternal aggression induces depressive-like behavior and increases startle in adult female rats , 2012, Behavioural Brain Research.

[24]  J. Garber Depression in children and adolescents: linking risk research and prevention. , 2006, American journal of preventive medicine.

[25]  R. Romeo Adolescence: a central event in shaping stress reactivity. , 2010, Developmental psychobiology.

[26]  G. Neigh,et al.  Behavioral effects of chronic adolescent stress are sustained and sexually dimorphic , 2011, Hormones and Behavior.

[27]  B. McEwen,et al.  Stress history and pubertal development interact to shape hypothalamic-pituitary-adrenal axis plasticity. , 2006, Endocrinology.

[28]  S. Bhatnagar,et al.  The physical context of previous stress exposure modifies hypothalamic–pituitary–adrenal responses to a subsequent homotypic stress , 2007, Hormones and Behavior.

[29]  I. Lucki The forced swimming test as a model for core and component behavioral effects of antidepressant drugs. , 1997, Behavioural pharmacology.

[30]  K. Miczek A new test for aggression in rats without aversive stimulation: Differential effects of d-amphetamine and cocaine , 1979, Psychopharmacology.

[31]  R. Valentino,et al.  Early Adolescence as a Critical Window During Which Social Stress Distinctly Alters Behavior and Brain Norepinephrine Activity , 2011, Neuropsychopharmacology.

[32]  L. Spear The adolescent brain and age-related behavioral manifestations , 2000, Neuroscience & Biobehavioral Reviews.

[33]  S. Bhatnagar,et al.  Enduring and sex-specific effects of adolescent social isolation in rats on adult stress reactivity , 2010, Brain Research.

[34]  K. Flannelly,et al.  Time course of postpartum aggression in rats (Rattus norvegicus). , 1987 .