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.