期刊
NEUROPSYCHOPHARMACOLOGY
卷 31, 期 1, 页码 139-150出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.npp.1300786
关键词
dopamine; microdialysis; speedball; cocaine; heroin; self-administration
资金
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS038231] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [R01DA013234, P50DA006634, K05DA000114, R01DA013772, R01DA012498] Funding Source: NIH RePORTER
- NIDA NIH HHS [P50 DA006634, R01 DA012498, DA13772, DA 06634, R01 DA013234, K05 DA000114, DA00114, DA 12498, DA 13234] Funding Source: Medline
- NINDS NIH HHS [NS38231, R01 NS038231] Funding Source: Medline
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.
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