Effects of nicotinic and NMDA receptor channel blockers on intravenous cocaine and nicotine self-administration in mice

Previous studies have indicated that blockade of N-methyl-D-aspartate (NMDA) subtype of glutamate receptors prevents acquisition of instrumental behaviors reinforced by food and drugs such as morphine and cocaine. The present study aimed to extend this evidence by testing whether NMDA receptor channel blocker, memantine, would exert similar effects on acquisition of cocaine and nicotine self-administration in mice. Inasmuch as memantine also acts as nicotinic receptor channel blocker, this study assessed the effects of mecamylamine and MRZ 2/621 that are more selective nicotinic blockers. Adult male Swiss mice were allowed to self-administer cocaine (0.8-2.4 mug/infusion) or nicotine (0.08-0.32 mug/infusion) during the 30-min test. Pretreatment with memantine (0.1-10 mg/kg) prevented acquisition of nicotine but not cocaine self-administration. Pretreatment with mecamylamine (0.3-3 mg/kg) and MRZ 2/621 (0.3-10 mg/kg) produced dose-dependent suppression of both cocaine and nicotine self-administration. Taken together with the previous reports, these results indicate that nicotinic receptor blockers antagonize acute reinforcing effects of cocaine while NMDA receptor blockade may have limited effectiveness. (C) 2004 Elsevier B.V. and ECNP. All rights reserved.