Nicotinic effects of tobacco smoke constituents in nonhuman primates

• Published in: Psychopharmacology Vol. 233; no. 10; pp. 1779 - 1789
• Main Authors: Desai, Rajeev I., Doyle, Michelle R., Withey, Sarah L., Bergman, Jack
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2016; Springer; Springer Nature B.V
• Subjects: Addictions; Addictive behaviors; Alkaloids - pharmacology; Anabasine - pharmacology; Animals; Behavior; Behavior, Addictive - chemically induced; Behavior, Animal - drug effects; Biomedical and Life Sciences; Biomedicine; Cotinine - pharmacology; Dose-Response Relationship, Drug; Experiments; Food; Health aspects; Laboratory animals; Male; Monkeys & apes; Neurosciences; Nicotiana - chemistry; Nicotine; Nicotine - analogs & derivatives; Nicotine - pharmacology; Original Investigation; Pharmacology/Toxicology; Primates; Psychiatry; Psychopharmacology; Pyridines - pharmacology; Saimiri; Smoke - analysis; Smoking; Tobacco smoke; United States > US; Minor tobacco alkaloids; Drug discrimination; Food-maintained behavior; Epibatidine; Nornicotine; Anabasine; Nonhuman primates; Anatabine; Myosmine; Nicotine
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-016-4238-5

Rationale Recent studies in rodents suggest that non-nicotine constituents of tobacco smoke (e.g., minor tobacco alkaloids) may promote tobacco consumption—either through their own pharmacological effects or by augmenting the effects of nicotine. However, there is scant information on the behavioral pharmacology of minor tobacco alkaloids in primate species. Objective The present studies were conducted to determine whether the minor tobacco alkaloids nornicotine, anabasine, anatabine, myosmine, and cotinine exhibit nicotine-like behavioral effects in squirrel monkeys. Methods Initial experiments were conducted to determine the effects of nicotine (0.032–1.0 mg/kg) and the minor tobacco alkaloids nornicotine (1–1.8 mg/kg), anabasine (0.1–1.0 mg/kg), anatabine (10–32 mg/kg), myosmine (0.32–1.8 mg/kg), and cotinine (10–180 mg/kg) on food-maintained performance ( n  = 4). Next, the ability of tobacco alkaloids to substitute for the α4β2-selective nicotinic agonist (+)-epibatidine in drug discrimination experiments was evaluated in a separate group of monkeys ( n  = 4). Results Results show that nicotine and each minor tobacco alkaloid except cotinine (a) produced dose-related decreases in food-maintained responding; (b) substituted for (+)-epibatidine and, in additional experiments, produced additive effects when combined with nicotine; (c) induced emesis or tremor at doses that reduced food-maintained responding and had (+)-epibatidine-like discriminative-stimulus effects; and (d) based on correlation with reported receptor binding affinities, likely produced their behavioral effects through α4β2 receptor mechanisms. Conclusion Selected minor tobacco alkaloids have nicotinic-like effects that may contribute to tobacco consumption and addiction.