Effects of an antitussive mixture and its constituents in rats discriminating methamphetamine from saline

The discriminative effects of over-the-counter antitussive syrup containing dihydrocodeine (DHC), methylephedrine (MEP), caffeine (CAF), and chlorpheniramine (CPA) were compared with those of methamphetamine (MA) in a drug discrimination experiment using rats. Rats were trained to discriminate the effects of MA at 0.5 mg/kg SC and saline for food reinforcement under the fixed-ratio 10 schedule in a two-lever operant chamber situation. In substitution testing using a cumulative dose procedure by the subcutaneous route, DHC (4 and 8 mg/kg, expressed hereafter as referred to cumulative dose) or CPA (16-64 mg/kg) individually did not produce MA lever selection. On the other hand, MEP (128 mg/kg) and CAF (64 mg/kg) produced MA lever selection 41.5 and 57.2% of the time, respectively. The complete mixture (16 mg/kg DHC + 32 mg/kg MEP + 33.2 mg/kg CAF + 6.4 mg/kg CPA) produced MA level selection 65.8% of the time. The partial mixture containing only MEP + CAF at the above doses produced MA lever selection 95.6% of the time. Thus, the complete mixture only partially substituted for MA in rats while the partial mixture containing MEP and CAF completely substituted for MA.