Thomas J Martin1, Susy A Kim, Yulia Lyupina, James E Smith. 1. Center for the Neurobiological Investigation of Drug Abuse, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083, USA. tjmartin@wfubmc.edu
Abstract
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 microg 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 [(3)H]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.
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 microg 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 [(3)H]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.
Authors: Valentina Sabino; Pietro Cottone; George F Koob; Luca Steardo; Mei J Lee; Kenner C Rice; Eric P Zorrilla Journal: Psychopharmacology (Berl) Date: 2006-10-18 Impact factor: 4.530
Authors: Jennifer L Cornish; Jaclyn M Lontos; Kelly J Clemens; Iain S McGregor Journal: Psychopharmacology (Berl) Date: 2005-01-29 Impact factor: 4.530