Comparative effects of dextromethorphan and dextrorphan on morphine, methamphetamine, and nicotine self-administration in rats

The effects of dextromethorphan and its metabolite dextrorphan on morphine, methamphetamine and nicotine self-administration and on responding for a n ondrug reinforcer (water) were assessed in rats. Both dextromethorphan and dextrorphan decreased morphine self-administration at 10-30 mg/kg, s.c., de creased methamphetamine self-administration at 20 and 30 mg/kg, s.c., and d ecreased nicotine self-administration at 5-30 mg/kg, s.c.; doses of both dr ugs less than 40 mg/kg, s.c. did not affect responding for water. The equal potencies of dextromethorphan and dextrorphan suggest mediation of these e ffects by a non-NMDA receptor mechanism, possibly involving blockade of alp ha3 beta4 nicotinic receptors. The results also suggest that dextromethorph an should be tested extensively as a potential treatment for diverse popula tions of drug-abusing patients. (C) 2001 Elsevier Science B.V. All rights r eserved.