REVERSAL OF OVERSHADOWING IN A DRUG MIXTURE DISCRIMINATION IN RATS

Previous studies have suggested that in some circumstances, learning p rocesses such as overshadowing may determine the effects that one drug has upon the response to another. The experiments described here exam ined overshadowing in rats trained to discriminate mixtures of nicotin e plus midazolam in two-lever operant procedures with food reinforceme nt. After training for 60 sessions, midazolam (0.32 mg/kg SC) overshad owed nicotine (0.32 mg/kg SC) so that the discriminative stimulus effe ct of nicotine seen in control rats trained with nicotine alone was ab olished (n = 8-10). In the next phase of the study, the discriminative response to midazolam in one group of mixture-trained rats was devalu ed by means of an extinction procedure which weakened the relationship between administration of midazolam and the response that was reinfor ced. Dose-response determinations then showed that the devaluation pro cedure had indeed attenuated the response to midazolam, whereas the pr eviously overshadowed response to nicotine was restored. Post-session injections of drugs were used to equate the pharmacological histories of the groups and the effects seen were therefore attributable to trai ning with the drugs and not simply to repeated exposure to them. Addit ionally, in the control rats trained with nicotine only (with midazola m given post-session), midazolam markedly reduced response rates, wher eas in the three groups of rats trained with the mixture, midazolam ha d little response rate-depressant effect; this observation suggests th at behaviourally contingent tolerance had developed to the response ra te-reducing effect of midazolam. Application of devaluation procedures in studies of the discriminative stimulus effects of single drugs wit h multiple effects may provide a means for manipulating the characteri stics of the discriminations obtained and for identifying individual e lements of the drug-produced stimulus complex.