Neuroscience
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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. ⋯ 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.
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Puberty is a period characterized by brain reorganization that contributes to the development of neural and behavioral responses to gonadal steroids. A single injection of the bacterial endotoxin, lipopolysaccharide (LPS), during the pubertal period decreases sexual receptivity in response to ovarian hormones in adulthood. Because chronic estradiol treatment alleviates depression-like symptoms in ovariectomized adult mice, we investigated the effect of pubertal LPS treatment on estradiol's antidepressant effects. ⋯ In contrast, in mice treated pubertally with LPS, estradiol strikingly increased the duration of immobility. No difference in body weight and in locomotion was found among the groups, suggesting that the differences in depression-like behavior were not due to differences in body weight or locomotor activity between LPS-treated and control mice. These results suggest that exposure to an immune challenge during the pubertal period alters the responsiveness of depression-like behavior to estradiol.
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Elevated ethanol use during adolescence, a potentially stressful developmental period, is accompanied by insensitivity to many aversive effects of ethanol relative to adults. Given evidence that supports a role for stress and the kappa opioid receptor (KOR) system in mediating aversive properties of ethanol and other drugs, the present study assessed the role of KOR antagonism by nor-binaltorphimine (nor-BNI) on ethanol-induced conditioned taste aversion (CTA) in stressed (exposed to repeated restraint) and non-stressed male rats (Experiment 1), with half of the rats pretreated with nor-BNI before stressor exposure. In Experiment 2, CTA induced by the kappa agonist U62,066 was also compared in stressed and non-stressed adolescents and adults. ⋯ This effect of nor-BNI was not seen in adolescents, findings that support a differential role for the KOR involvement in ethanol CTA in stressed adolescents and adults. Results from Experiment 2 revealed that all doses of U62,066 elicited aversions in non-stressed animals of both ages that were attenuated in stressed animals, findings that support a modulatory role for stress in aversive effects of KOR activation. Collectively, these results suggest that although KOR sensitivity appears to be reduced in stressed subjects, this receptor system does not appear to contribute to age differences in ethanol-induced CTA under the present test circumstances.
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Review
From the stressed adolescent to the anxious and depressed adult: investigations in rodent models.
Anxiety and depression are the most prevalent of the psychiatric disorders. The average age of onset of these disorders is in adolescence, and stressful experiences are recognized as an important pathway to such dysfunction. ⋯ The focus of the review is investigations in which adolescent rodents were exposed to chronic stressors, describing our research using social instability stress and that of other researchers using various social and non-social stressors. The evidence to date suggests stress in adolescence alters the trajectory of brain development, and particularly that of the hippocampus, increasing anxiety and depressive behaviour in adulthood.
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Chronic stress is known to modulate cannabinoid CB1 receptor binding densities in corticolimbic structures, in a region-dependent manner; however, the ontogeny of these changes and the degree to which they recover following exposure to stress have yet to be determined. To this extent, we examined both the immediate and sustained effects (following a 40-day recovery period) of a repeated restraint stress paradigm (30-min restraint/day for 10 days) on CB1 receptor binding in the prefrontal cortex (PFC), hippocampus and amygdala in both adolescent (stress onset at post-natal day [PND] 35) and adult (stress onset at PND 75) male Sprague-Dawley rats. Consistent with previous reports, we found that repeated stress in adult rats resulted in an increase in CB1 receptor binding in the PFC, a reduction in CB1 receptor binding in the hippocampus and no effect in the amygdala. ⋯ Adolescents similarly exhibited this rebound increase in hippocampal CB1 receptor binding, despite a lack in immediate downregulation following repeated restraint. Of particular interest, adolescents exposed to stress were found to have a sustained downregulation of prefrontocortical CB1 receptors in adulthood, which may relate to some of the reported sustained behavioral effects of stress in adolescence. Collectively, these data indicate that the effects of chronic stress on cannabinoid CB1 receptor binding are modulated by the age of stress exposure and period of recovery following the cessation of stress.