ANTAGONISM OF AND AND AND-OR DRUG MIXTURE DISCRIMINATIONS IN RATS

It has been suggested that use of the AND-OR training method may be as sociated with an enhancement of the pharmacological specificity of dis criminations based on mixture of drugs. Rats were trained to discrimin ate a mixture of nicotine (0.4 mg/kg s.c.) plus midazolam (0.2 mg/kg s .c.) from saline (AND-discrimination n = 8) or to discriminate the mix ture from either drug alone (AND-OR discrimination, n = 6). The studie s used two-lever operant procedures with food reinforcers presented on a tandem schedule. After discriminations were acquired to 80% accurac y, the nicotine antagonist mecamylamine (0.03-1.0 mg/kg s.c.) and the benzodiazepine antagonist flumazenil (0.32-10 mg/kg i.p.) were tested on the response to the mixture of nicotine plus midazolam. The antagon ist effects of either mecamylamine or flumazenil given alone were more marked in rats trained under the AND-OR procedure than in rats traine d on the AND-discrimination. Similarly, the antagonist effects of mixt ures of mecamylamine plus flumazenil were much more potent under the A ND-OR than under the AND-discrimination procedure. The AND-OR method r educed the dose of the antagonist mixture needed to produce complete b lock by a factor of about 10, as compared with the AND-discrimination. These striking differences in sensitivity to antagonists support the view that AND-OR or related procedures may enhance the pharmacological specificity of complex drug discriminations. Copyright (C) 1997 Elsev ier Science Ireland Ltd.