Enkephalin and dynorphin mRNA expression are associated with resilience or vulnerability to chronic social defeat...

There are important and enduring differences between individuals in the magnitude of all aspects of the stress response. Among the neuropeptide systems, the endogenous opioids enkephalin (ENK) and dynorphin (DYN), are very interesting candidates to participate in the naturally occurring variations in coping styles and to determine the individual capacity for adaptation during chronic stress exposure. Under chronic social stress exposure, we hypothesize that changes in the ENKergic vs DYNergic neuronal systems within specific nuclei of the basal forebrain contribute to naturally occurring variations in coping styles and will determine individual capacities for stress adaptation. Sprague-Dawley rats were exposed to a resident-intruder model of defeat for 7 days. The average latency to be defeated over seven consecutive days was calculated for each intruder rat. Based on this distribution, we chose an average defeat latency of 350s as a cutoff criterion to define resilient and vulnerable rats. A subpopulation assumed a subordinate posture in a relatively short latency (<350s, SL) and the other subpopulation resisted defeat resulting in longer latencies (>350s, LL) to assume this posture and were identified as being vulnerable and resilient respectively. Rats were euthanized 24h after the last stress session. ENK mRNA expression was lower in the basolateral nucleus of the amygdala in vulnerable compared to control and resilient individuals. In contrast, there was no difference between resilient and control individuals. DYN mRNA is increased only within the dorsal and medial shell of the NAc of vulnerable rats compared to control individuals. There was no difference between resilient and control individuals. DYN mRNA is increased in resilient individuals in the central area of the striatum, caudal part, compared to control individuals. DYN is also increased in medial area of the striatum, caudal part in resilient and vulnerable compared to control individuals. These results have broad implications for understanding the functional roles of opioid neurotransmission following repeated social stress and suggest that ENK could facilitate the adaptation of behavioral responses by opposition to the DYN neurotransmission that appears to promote maladaptive behavioral response to chronic social stress.