title: Self-administered heroin and cocaine combinations in the rat: additive reinforcing effects-supra-additive effects on nucleus accumbens extracellular dopamine.
abstract: The concurrent use of cocaine and opiate combinations (speedball) has increased since the 1970s and now represents a growing subset of intravenous drug abusers. An isobolographic analysis was applied to the ascending limb of the dose-effect curves for rat self-administration of cocaine, heroin, and their combination to determine the nature of the interaction. The addition of heroin to cocaine shifted the dose-effect curve for self-administration to the left, and the modulation in reinforcing efficacy of the combination of cocaine and heroin was found to be additive. A second experiment used microdialysis to determine the effects of this drug combination on nucleus accumbens (NAc) extracellular levels of dopamine ([DA](e)) in rats self-administering low doses of cocaine, heroin, or cocaine/heroin combinations. These doses of cocaine and cocaine/heroin combinations significantly increased NAc [DA](e), while heroin alone did not. The ratio of the % baseline of [DA](e) (or the dialysate concentrations of DA) to cocaine in the dialysate was higher during self-administration of cocaine/heroin combinations than with cocaine alone. These data indicate that although the interaction between cocaine and heroin in maintaining self-administration is additive, a potentiation of NAc dopaminergic neurotransmission is present, suggesting that NAc [DA](e) may not be a direct measure of reinforcing efficacy and/or it is not central to the mediation of the self-administration of this drug combination.
authors.affiliation: Center for the Neurobiological Investigation of Drug Abuse, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Wake Forest University, Winston-Salem, NC, USA. jamsmith@wfubmc.du
authors.forename: James E
authors.initials: JE
authors.lastname: Smith
authors.forename: Conchita
authors.initials: C
authors.lastname: Co
authors.forename: Michael D
authors.initials: MD
authors.lastname: Coller
authors.forename: Scott E
authors.initials: SE
authors.lastname: Hemby
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Martin
mesh_terms: D000818:Animals; D019970:Cocaine-Related Disorders / Q000523:psychology*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006556:Heroin Dependence / Q000523:psychology*; D007262:Infusions, Intravenous; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D004298:Dopamine