Although caution should be used when interpreting the relationships between behavior and mRNA expression (reflecting protein biosynthesis but not function) of any genes, the study of gene expression or peptide data in animals with established drug-seeking vulnerabilities provide useful information about a potential role of individual variations in response to stress-induced relapse. Both reduced availability of D2 receptor binding and decreased D2 gene expression in the striatum have been consistently associated with heroin cravings in humans [e.g., 38, 39] and cocaine seeking in animals [e.g., 25, 26]. In the present study, we observed a down-regulation of CPu D2 mRNA levels in the H-RI rats. Reduced D2 availability resultant from the decreased D2 gene expression could possibly be involved in the seeking action of heroin in the H-RI rats. In support of this concept, correlation analysis between the active lever responding during foot shock-induced reinstatement session and the CPu D2 mRNA levels revealed that the H-RI rats seeking relatively more heroin showed relative lowered CPu D2 mRNA levels.
