In this study, we tested whether individual differences in stress responsive gene expressions would be associated with stress-induced vulnerability to heroin-seeking behavior. In the behavioral experiment, animals that self-administered heroin reliably displayed reinstatement of operant responding induced by acute foot-shock stress, but large individual differences were noted. Therefore, we used the median-split approach [27] to distinguish between the high (H-RI) and low reinstatement (L-RI) groups. The H-RI and L-RI groups were compared for their behavioral histories, including total heroin intake and active/inactive lever responding during self-administration sessions, and extinction responding, as well as heroin priming-induced reinstatement after the foot shock reinstatement. Finally, the mRNA levels of stress responsive genes in multiple brain regions were analyzed among the H-RI, L-RI and heroin self-administration non-responders (NR) groups.
