L. Pulvirenti et al., DEXTROMETHORPHAN REDUCES INTRAVENOUS COCAINE SELF-ADMINISTRATION IN THE RAT, European journal of pharmacology, 321(3), 1997, pp. 279-283
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.