The objective of this study is explore whether individual differences in the vulnerability to drug relapse after comparable histories of drug exposure may be related to individual differences in key stress-responsive neurochemical systems. For this purpose, we specifically designed a set of novel experiments in rats to determine if individual differences in stress-induced heroin-seeking would be associated with differences in the expression of central AVP, POMC, or orexin genes. In the present study, rats were trained to intravenously self-administer heroin for 7 days and, after a 4-day period of extinction, they were tested for reinstatement of lever pressing (heroin –associate lever with saline available only) induced by acute (15-min) intermittent foot shock stress [6, 24]. Following this test, rats were divided into high and low reinstatement responders (H-RI and L-RI) to acute foot shock stress. In order to verify the specificity of the stress-defined H-RI and L-RI groups, all rats were also tested for reinstatement of lever pressing induced by a heroin prime. Nine days after heroin self-administration, specific brain regions were collected to quantify AVP, POMC and orexin gene
