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 beta-funaltrexamine.
BACKGROUND
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.


OBJECTIVE
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.
Martin
Thomas J
TJ
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
Kim
Susy A
SA
Lyupina
Yulia
Y
Smith
James E
JE
D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D003932:Heroin / Q000008:administration & dosage*; D007276:Injections, Intraventricular; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D017450:Receptors, Opioid, mu / Q000502:physiology*; D012054:Reinforcement, Psychology; D012646:Self Administration
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009271:Naltrexone; D003932:Heroin; C024524:beta-funaltrexamine