title: Microinjections of an opiate receptor antagonist into the bed nucleus of the stria terminalis suppress heroin self-administration in dependent rats.
abstract: Recent anatomical evidence suggests that the shell of the nucleus accumbens, the bed nucleus of the stria terminalis, and the central nucleus of the amygdala, together referred to as the extended amygdala, may play a role in opiate dependence. The bed nucleus of the stria terminalis and the shell of the nucleus accumbens have a moderately high density of opiate receptors, which allows for manipulation of opiate neurotransmission with receptor antagonists. The goal of this study was to determine the role these regions play in opiate reinforcement, and whether dependence alters the reinforcing effects of opiates by examining the effect of local administration of the opiate receptor antagonist methylnaloxonium on heroin self-administration in dependent and nondependent rats. Previous studies revealed that blockade of the reinforcing effects of opiates with systemic administration of opiate receptor antagonists results in an increase in heroin self-administration in nondependent rats, and a greater increase in dependent rats. In the present study, methylnaloxonium dose-dependently suppressed heroin intake when injected into the bed nucleus of the stria terminalis and shell of the nucleus accumbens of dependent rats, and had no effect in nondependent rats. These results demonstrate that opiate receptors in parts of the extended amygdala may be responsible for the reinforcing effects of opiates in dependent animals and suggest that activity in this system may be recruited during the development of dependence.
authors.affiliation: Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA. john_r.walker@nifg.novartis.com
authors.forename: J R
authors.initials: JR
authors.lastname: Walker
authors.forename: S H
authors.initials: SH
authors.lastname: Ahmed
authors.forename: K N
authors.initials: KN
authors.lastname: Gracy
authors.forename: G F
authors.initials: GF
authors.lastname: Koob
mesh_terms: D000818:Animals; D003932:Heroin / Q000008:administration & dosage*; D006556:Heroin Dependence / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D008845:Microinjections; D009270:Naloxone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009292:Narcotic Antagonists; D009294:Narcotics / Q000008:administration & dosage*; D009714:Nucleus Accumbens / Q000503:physiopathology; D000644:Quaternary Ammonium Compounds; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D012686:Septal Nuclei / Q000503:physiopathology*
chemical_list: D009292:Narcotic Antagonists; D009294:Narcotics; D000644:Quaternary Ammonium Compounds; D009270:Naloxone; D003932:Heroin; C041269:N-methylnaloxone