No 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.

No abstract

No abstract

Corticotropin-releasing factor (CRF) is a neurohormone that mediates stress, anxiety, and affects serotonergic activity. Studies have shown that CRF has dose-dependent opposing effects on serotonergic activity. This effect has been hypothesized to be differentially mediated by CRF 1 and CRF 2 receptors in the dorsal raphé nucleus. We directly tested this hypothesis by using in vivo microdialysis to determine the effects of CRF and CRF antagonists in the dorsal raphé nucleus on serotonin (5-HT) release in the nucleus accumbens, a brain region implicated in the neuropathology of stress-related psychiatric disorders. Male urethane-anesthetized rats were implanted with a microdialysis probe into the nucleus accumbens, and CRF (0, 100 or 500 ng) was infused into the dorsal raphé. Infusion of CRF into the dorsal raphé nucleus had dose-dependent opposite effects, with 100 ng of CRF significantly decreasing 5-HT levels in the nucleus accumbens and 500 ng CRF significantly increasing accumbal 5-HT levels. In subsequent experiments, the raphé was pre-treated with the CRF 1 receptor antagonist antalarmin (0.25 µg) or the CRF 2 receptor antagonist antisauvigine-30 (ASV-30; 2 µg) prior to CRF infusion. Antagonism of CRF 1 receptors in the dorsal raphé nucleus abolished the decrease in accumbal 5-HT levels elicited by 100 ng CRF, and CRF 2 receptor antagonism in the raphé blocked the increase in accumbal 5-HT levels elicited by 500 ng CRF. These results suggest that the opposing effects of dorsal raphé CRF on 5-HT release in the nucleus accumbens are dependent on differential activation of CRF 1 and CRF 2 receptors in the dorsal raphé nucleus.