Adolescent male rats exposed to social defeat exhibit altered anxiety behavior and limbic monoamines as adults.

Abstract

Social stress in adolescence is correlated with emergence of psychopathologies during early adulthood. In this study, we investigated the impact of social defeat stress during mid-adolescence on adult male brain and behavior. Adolescent male Sprague-Dawley rats were exposed to repeated social defeat for five days while controls were placed into a novel empty cage. When exposed to defeat-associated cues as adults, previously defeated rats showed increased risk assessment and behavioral inhibition, demonstrating long-term memory for the defeat context. However, previously defeated rats exhibited increased locomotion in both elevated plus maze and open field tests, suggesting heightened novelty-induced behavior. Adolescent defeat also affected adult monoamine levels in stress-responsive limbic regions, causing decreased medial prefrontal cortex dopamine, increased norepinephrine and serotonin in the ventral dentate gyrus, and decreased norepinephrine in the dorsal raphe. Our results suggest that adolescent social defeat produces both deficits in anxiety responses and altered monoaminergic function in adulthood. This model offers potential for identifying specific mechanisms induced by severe adolescent social stress that may contribute to increased adult male vulnerability to psychopathology.

Adolescent social stress does not necessarily lead to a compromised adaptive capacity during adulthood: A study on the consequences of social stress in rats

“…Although this seems to be in contrast with some previous findings (Avital and Richter-Levin, 2005;Vidal et al, 2007;Watt et al, 2009;Buwalda et al, 2011), it does clearly indicate the relatively high resilience of adolescent rats to lastingly develop behavioral and neurobiological stress pathologies. More studies examining and comparing acute and long-term effects of social and non-social stressors at different developmental stages under social as well as non-social housing conditions in the framework of the match-mismatch hypothesis are warranted before definite conclusions can be drawn concerning the sensitivity of specific age groups with regard to stress and its long-term consequences.…”

“…It is possible that the period between PND 35 and 42 represents a transition period during which adolescents move from one behavioral response to another and this could explain the lack of lasting behavioral changes in the present study. In another study applying social stress (Watt et al, 2009), it was shown that daily social defeat from PND 35 to 40 surprisingly caused a decreased anxiety in the elevated plus maze and an increased exploratory activity in the open field at PND 56. Only anxiety behavior in the context of the previous defeat stress increased.…”

“…Also some mild changes in brain monoamine levels were detected at PND 63 in a small part of the brain areas analyzed. In that study adolescents were also socially housed after the defeat experiences (Watt et al, 2009).…”

“…In male laboratory rodents the best equivalent of bullying is social defeat in the resident/ intruder test (Koolhaas et al, 1997). In the resident/ intruder test, the intruder is repeatedly subjected to attacks and threats from the dominant resident, and these attacks often persist even after the intruder signals defeat by displaying behavioral submission, similar to victims of bullying who are harassed and assaulted even though they do their utmost to avoid provoking the bully (Bjorkqvist, 2001;Vidal et al, 2007;Watt et al, 2009). The social defeat paradigm has been used successfully in adult laboratory rodents to elucidate some of the relevant neurobiological, physiological and behavioral changes caused by acute or chronic social defeat experience (Tornatzky and Miczek, 1993;Meerlo et al, 1996;Buwalda et al, 1999).…”

CRHR1 links peripuberty stress with deficits in social and stress-coping behaviors

“…In fact, stress during childhood and puberty e termed hereafter as the peripubertal period e has been associated with psychopathology later in life (Heim and Nemeroff, 2001;Watt et al, 2009). The peripubertal period is a biological transitional phase involving adaptations in hormonal systems and neural circuits, including those related to stress and the development of emotionality (Spear, 2009;Romeo, 2010).…”