Effects of ethanol on cocaine discrimination in rats.
Ethanol and cocaine are frequently abused in combination, but little is known about how the subjective effects of the two drugs interact. The ability of ethanol and other GABA(A)-active compounds to alter the discriminative stimulus effects of cocaine was tested. Male Sprague-Dawley rats were trained to discriminate cocaine (10 mg/kg ip) from saline using either single- or cumulative-dosing methods. In single-dose testing, ethanol (0.1-0.5 g/kg) dose-dependently decreased cocaine-appropriate responding following the training dose of cocaine. Ethanol (0.5 g/kg) produced a rightward shift in the cocaine cumulative dose-effect curve. Ethanol (0.1-1.0 g/kg) failed to substitute for the discriminative stimulus effects of cocaine and the higher doses (1-2 g/kg) completely suppressed responding. Indirect GABA(A) agonists diazepam (benzodiazepine site) and pentobarbital (barbiturate site) did not block the discriminative stimulus effects of cumulative doses of cocaine. The GABA(A) antagonist pentylenetetrazol (PTZ) (10-40 mg/kg) did not substitute for cocaine. These findings suggest that ethanol can modulate the discriminative stimulus effects of cocaine, and that these effects may not be mediated by the actions of ethanol at the GABA(A) receptor.
Gatch
Michael B
MB
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA. mgatch@hsc.unt.edu
Youngblood
Bradley D
BD
Forster
Michael J
MJ
D000818:Animals; D003042:Cocaine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D004193:Discrimination Learning / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration / Q000379:methods / Q000523:psychology
D000431:Ethanol; D003042:Cocaine