DEXTROMETHORPHAN REDUCES INTRAVENOUS COCAINE SELF-ADMINISTRATION IN THE RAT

Citation
L. Pulvirenti et al., DEXTROMETHORPHAN REDUCES INTRAVENOUS COCAINE SELF-ADMINISTRATION IN THE RAT, European journal of pharmacology, 321(3), 1997, pp. 279-283
Citations number
25
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00142999
Volume
321
Issue
3
Year of publication
1997
Pages
279 - 283
Database
ISI
SICI code
0014-2999(1997)321:3<279:DRICSI>2.0.ZU;2-7
Abstract
Dextromethorphan is a widely used antitussive agent with non-competiti ve antagonistic effects at the excitatory amino acid receptors of the NMDA type. Since excitatory amino acid neurotransmission has been impl icated in cocaine dependence, the aim of the present study was to eval uate the effects of acute systemic administration of dextromethorphan in rats trained to self-administer cocaine intravenously. The experime nts were designed to evaluate the effects of dextromethorphan on respo nding for cocaine and cocaine reward magnitude. The hypothesis was tha t dextromethorphan could attenuate specific aspects of cocaine-seeking behavior thus providing a preclinical rationale for its clinical use. The results reported reveal that acute pretreatment with dextromethor phan (10-50 mg/kg i.p.) significantly reduced cocaine self-administrat ion in rats self-administering the drug intravenously in a simple cont inuous reinforcement schedule. In addition, acute pretreatment with an effective dose of dextromethorphan (25 mg/kg) decreased cocaine self- administration in rats tested at various doses of cocaine (0.12-0.5 mg /injection). Finally, dextromethorphan (25 mg/kg) also reduced the abs olute reward magnitude of cocaine as measured by responding for cocain e in a progressive ratio schedule. These results encourage further exp erimental and clinical studies to evaluate the potential use of dextro methorphan during various phases of the natural history of cocaine dep endence in humans.