Caffeine-phenylethylamine combinations mimic the amphetamine discriminative cue.

Although caffeine-phenylethylamine combinations are widely available as over-the-counter medications or as "legal" stimulants, little information is available concerning their behavioral pharmacology or abuse potential. In the present study, rats were trained in a food-reward, two-lever operant drug discrimination paradigm to differentially respond after saline or 0.5 mg/kg amphetamine injections. Tests for generalization to the amphetamine cue indicated only modest amphetamine-lever responding at various doses of caffeine alone or at various doses of ephedrine/phenylpropanolamine (PPA) combinations, but complete generalization to the training cue was found with higher doses of the triple combination (caffeine, ephedrine, and PPA) or with caffeine-ephedrine or caffeine-PPA combinations. All drugs produced response rate decreases at higher doses. These data clearly indicate that certain "legal" stimulants mimic the amphetamine cue and suggest that caffeine may interact additively with phenylethylamines to produce the cue.