Individual differences in gene expression of vasopressin, D2 receptor, POMC and orexin: Vulnerability to relapse to heroin-seeking in rats

Individual vulnerability to stress-induced relapse during abstinence from chronic heroin exposure is a key feature of opiate addiction, with limited studies on this topic. Arginine vasopressin (AVP) and its V1b receptor, components of the brain stress responsive systems, play a role in heroin-seeking behavior triggered by foot shock (FS) stress in rats. In this study, we tested whether individual differences in the FS-induced heroin-seeking were associated with alterations of AVP and V1b, as well as other stress responsive systems, including pro-opiomelanocortin (POMC), orexin, plasma ACTH and corticosterone, as well as dopamine D2 receptor (D2) and plasma prolactin. Sprague-Dawley rats were subjected to 3-hour intravenous heroin self-administration (SA) and then tested in extinction, and FS-induced and heroin priming-induced reinstatements. The rats that self-administered heroin were divided into high and low reinstatement responders induced by FS (H-RI; L-RI). Over SA sessions, both the H-RI and L-RI displayed similar active lever responding, heroin infusion and total heroin intake. Compared to the L-RI, however, the H-RI showed greater active lever responses during stress-induced reinstatement, with higher AVP mRNA levels in medial/basolateral amygdala and lower D2 mRNA levels in caudate putamen. However, heroin priming resulted in similar reinstatement in both groups and produced similarly low POMC and high orexin mRNA levels in hypothalamus. Our results indicate that: 1) enhanced amygdalar AVP and reduced striatal D2 expression may be related to individual vulnerability to stress-induced reinstatement of heroin- seeking; and 2) heroin abstinence-associated alterations of hypothalamic orexin and POMC expression may be involved in drug priming-induced heroin-seeking.