Dextromethorphan alters the reinforcing effect of cocaine in the rat

Dextromethorphan (DM) at supra-antitussive doses produces psychotomimetic effects in humans. In order to achieve a better understanding of the pharmacological mechanisms responsible for the behaviors induced by DM, we examined the effects of DM on the intravenous self-administration of cocaine in the rat. The effects of DM (40 mg/kg, p.o.) on responding for 0.5, 0.25, 0.125, 0.06 and 0.03 mg/kg/infusion of cocaine was assessed. DM decreased the rate of responding for higher doses of cocaine (0.5, 0.25 and 0.125 mg/kg/infusion), and increased the rate of responding for lower doses of cocaine (0.06 and 0.03 mg/kg/infusion), suggesting that DM shifted the dose-response curve for cocaine self-administration to the left. Therefore, our results indicate that the sensitivity to cocaine's behavioral effects appears to be enhanced by DM.