title: The effects of intravenous heroin administration on extracellular nucleus accumbens dopamine concentrations as determined by in vivo microdialysis.
abstract: Dopaminergic innervations of the nucleus accumbens (NAcc) have a significant role in the brain processes underlying the reinforcing actions of abused drugs. In addition to the evidence from selective lesions and receptor antagonists, recent determinations of increased extracellular dopamine concentrations ([DA]e) in this structure during cocaine and ethanol self-administration have extended this notion. This study was undertaken to determine if the reinforcing effects of heroin were similarly correlated with changes in [DA]e in the NAcc using in vivo microdialysis. In the first experiment, naive rats were randomly divided into three groups and administered either two i.v. infusions of saline (n = 6) or heroin (5.4, 18 or 30 micrograms/infusion; n = 6, 8 and 6, respectively) 1 hr apart. [DA]e in the NAcc was significantly increased in a dose-dependent manner after response-independent heroin administration. In the second experiment, responding was engendered and maintained with 5.4, 18 or 30 micrograms/infusion of heroin (i.v.; n = 4, 5 and 5/group, respectively) under a fixed ratio 10 (FR10) schedule of reinforcement. After stable baselines of heroin intake were obtained, microdialysis samples were collected from the NAcc during the self-administration session. [DA]e did not significantly differ from baseline during self-administration in any of the groups. The increase in NAcc [DA]e following acute response-independent heroin administration is consistent with previously published reports. However, the latter results do not support the hypothesis that NAcc dopamine is critically involved in the processes underlying heroin self-administration. In summary, the results indicate that in vivo neurochemical data obtained from acute experimenter-administered heroin can not be equated with that obtained during heroin self-administration.
authors.affiliation: Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Hemby
authors.forename: T J
authors.initials: TJ
authors.lastname: Martin
authors.forename: C
authors.initials: C
authors.lastname: Co
authors.forename: S I
authors.initials: SI
authors.lastname: Dworkin
authors.forename: J E
authors.initials: JE
authors.lastname: Smith
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D004563:Electrochemistry; D003932:Heroin / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012646:Self Administration
chemical_list: D003932:Heroin; D002118:Calcium; D004298:Dopamine