Differential involvement of mu-opioid receptors in the rostral versus caudal nucleus accumbens in the reinforcing effects of heroin in rats:: evidence from focal injections of β-funaltrexamine

Rationale: The nucleus accumbens is a diverse and heterogeneous structure along its rostrocaudal axis. The influence of specific subpopulations of mu-opioid receptors within the NAcc in heroin self-administration has not been documented. Objectives: This study was undertaken to investigate the involvement of subregions of the NAcc in heroin self-administration in rats. Methods: Male rats were trained to self-administer heroin and then given beta-FNA, an irreversible mu-opioid receptor antagonist, into either the rostral or caudal portion of the NAcc. Results: beta-FNA (0.25-2.5 nmol) attenuated heroin self-administration in a dose-responsive manner when given into the caudal but not rostral NAcc. The number of infusions of 18 mug of heroin self-administered was increased by 50-100%. This effect persisted for up to 17 days following administration of the highest dose. These doses of beta-FNA were found to decrease [H-3]DAMGO binding in a dose-responsive manner and the effect was confined to the NAcc, as nearby structures such as the caudate putamen and olfactory tubercles were unaffected. The effect of beta-FNA (2.5 nmol) administration into the caudal NAcc was also assessed on the dose-effect curve for heroin. This dose apparently shifted the dose-effect Curve to the right initially, followed by an apparent upward shift for up to 17 days after beta-FNA administration. Conclusions: The caudal portion of the NAcc and its output sites merit further investigation regarding the reinforcing effects of heroin.