Reinforcing Effects of Nicotinic Compounds: Intravenous Self-administration in Drug-Naive Mice

Abstract

The nicotinic compounds (−)-cytisine, (−)-lobeline, (±)-epibatidine, (S)-3methyl-5-(1-methyl-2-pyrrolidinyl)isoaxzole (ABT-418) , ( −)-nicotine, and cocaine were compared in an acute self-administration model using drug-naive mice that could self-administer intravenous infusions contingent on nose poking (fixed ratio 1 with no time out). Although the nose pokes of yoked control mice were unaffected by unit dose, inverted U-shaped unit dose–response curves were seen with cocaine (up to 0.26 mg/kg/infusion), nicotine (up to 0.175 mg/kg/infusion), cytisine (up to 0.125 mg/kg/infusion), and lobeline (up to 1.25 mg/kg/infusion) in mice receiving infusions contingent upon nose poke responses. Epibatidine (up to 1.25 μg/kg/infusion) and ABT-418 (up to 0.125 mg/kg/infusion) failed to exhibit inverted U-shaped unit dose–response curves. The present studies demonstrate that cytisine and lobeline, but not ABT-418 or epibatidine, were self-administered by drug-naive mice in a manner similar to cocaine and nicotine. These findings are discussed in terms of potency and selectivity at the α 4β 2 nicotinic acetylcholine receptor subunit combination.