Discriminative stimulus effects of intravenous l-nicotine and nicotine analogs or metabolites in squirrel monkeys

Abstract

Squirrel monkeys were trained to emit one response after IV administration of l-nicotine (0.4 or 0.2 μmol/kg) and a different response after IV administration of saline. After stable discriminative performances were established, subjects were tested with cumulative doses of l-nicotine (0.02–2.2 μmol/kg), d-nicotine (0.02–19.7 μmol/kg), l-nornicotine (0.2–12.0 μmol/kg), l-cotinine (56.8–567.5 μmol/kg), and dl-anabasine (0.6–19.7 μmol/kg). All of the drugs produced dose-related increases in the percentage of drug-appropriate responses emitted, from predominately saline-appropriate responses after low doses, to predominately drug-appropriate responses at the highest doses studied. Relative potency comparisons indicated that l-nicotine was 28 times more potent than d-nicotine, 29 times more potent than l-nornicotine, and approximately 2000 times more potent than l-cotinine. Each of the drugs also produced decreases in rates of responding, with potency order similar to that obtained for the discriminative effects. The effects of l-cotinine may be attributed to trace amounts of l-nicotine, which existed within the l-cotinine. The effects of dl-anabasine were lethal in one subject and were consequently not studied in the other subjects.