Drug discrimination studies in rats with caffeine and phenylpropanolamine administered separately and as mixtures

The discriminative stimulus effects of mixtures of caffeine and phenylpropanolamine (PPA) have been investigated because these drugs have been abused together. Rats were trained to discriminate caffeine (20 mg/kg), PPA (20 mg/kg), or a mixture of both drugs, from saline in a two-bar operant conditioning procedure with food reinforcers presented on a tandem VI-FR schedule. Discriminations of mixture, caffeine alone and PPA alone were 90% accurate after 40 sessions. Generalisation to both PPA and caffeine was weak (25-47%) at the doses used in the training mixture, although there was almost complete generalisation to larger doses of PPA. Under these conditions, there was a possible synergistic interaction between caffeine and PPA because the discriminative effect of the mixture could not be fully explained by the combined effects of its component drugs. However, in rats trained on caffeine, PPA had no effect on the dose-response relationship for caffeine; similarly, in rats trained on PPA, caffeine had no effect on the dose-response relationship for PPA (no synergism or antagonism). Generalisation to (+)-amphetamine and cocaine was weakest in rats trained on caffeine, was partial in rats trained on the mixture, and was complete in rats trained on PPA; thus, the mixture of caffeine and PPA was not more like cocaine or amphetamine than PPA alone. The results are in agreement with reports that caffeine and PPA may interact in a complex manner, but do not support the view that the interaction enhances their resemblance to highly abused stimulants such as amphetamine and cocaine.