Discriminative stimulus effects of intravenous l-nicotine and nicotine analogs or metabolites in squirrel monkeys.
Squirrel monkeys were trained to emit one response after IV administration of l-nicotine (0.4 or 0.2 mumol/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 mumol/kg), d-nicotine (0.02-19.7 mumol/kg), l-nornicotine (0.2-12.0 mumol/kg), l-cotinine (56.8-567.5 mumol/kg), and dl-anabasine (0.6-19.7 mumol/kg). All of the drugs produced dose-related increases in the percentage of drug-appropriate responses emitted, from predominantly saline-appropriate responses after low doses, to predominantly 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.
Takada
K
K
Preclinical Pharmacology Branch, NIDA Addiction Research Center, Baltimore, MD 21224.
Swedberg
M D
MD
Goldberg
S R
SR
Katz
J L
JL
D000691:Anabasine / Q000494:pharmacology; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D003367:Cotinine / Q000494:pharmacology; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D008297:Male; D009538:Nicotine / Q000031:analogs & derivatives / Q000494:pharmacology*; D012055:Reinforcement Schedule; D012453:Saimiri; D013237:Stereoisomerism
D009538:Nicotine; C005311:nornicotine; D003367:Cotinine; D000691:Anabasine