Drug interactions in the reinforcing effects of over-the-counter cough syrups

Drug interactions in reinforcin effects of over-the-counter cough syrups were investigated by utilizing place preference conditioning in rats. Dihydrocodeine (2 mg/kg, IP) induced a small, non-significant place preference. On the other hand, concurrent dosing of dihydrocodeine (2 mg/kg, IP) and a mixture (SC) of methylephedrine (4 mg/kg), caffeine (4 mg/kg) and chlorpheniramine (0.8 mg/kg) produced a significant place preference, the mean conditioning score in this group being about 3 times higher than that in the dihydrocodeine alone group. The potentiation of dihydrocodeine-conditioned place preference was observed by combination with chlorpheniramine (0.8 mg/kg, SC) alone as well as with the mixture, but neither with methylephedrine (4 mg/kg, SC) nor with caffeine (4 mg/kg, SC). Chronic infusion of the dopamine D1 receptor antagonist SCH23390 (1.0 mg/kg/day, SC) during conditioning abolished the appetitive effects of dihydrocodeine combined with chlorpheniramine. In conclusion, it is suggested that the potentiation of appetitive effects of dihydrocodeine is mostly due to chlorpheniramine among three ingredients in the cough syrups, and that the dopaminergic system, especially D1 receptor, may play an important role in the potentiation effect of chlorpheniramine on the reinforcing effects of dihydrocodeine.