Influence of experimental history on nicotine self-administration in squirrel monkeys

• Published in: Psychopharmacology Vol. 233; no. 12; pp. 2253 - 2263
• Main Authors: Desai, Rajeev I., Sullivan, Katherine A., Kohut, Stephen J., Bergman, Jack
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2016; Springer; Springer Nature B.V
• Subjects: Alkaloids - administration & dosage; Animals; Behavior; Behavior, Addictive - psychology; Behavior, Animal - drug effects; Behavior, Animal - physiology; Biomedical and Life Sciences; Biomedicine; Cocaine; Cocaine - administration & dosage; Dosage and administration; Dose-Response Relationship, Drug; Drug use; Eating - drug effects; Eating - physiology; Eating - psychology; Experiments; Laboratory animals; Male; Monkeys & apes; Neurosciences; Nicotine; Nicotine - administration & dosage; Original Investigation; Pharmacology/Toxicology; Psychiatry; Pyridines - administration & dosage; Reinforcement, Psychology; Saimiri; Self Administration; Squirrel monkeys; Self-administration; Nonhuman primates; Anatabine; Cocaine; Experimental history; Minor tobacco alkaloid; Nicotine
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-016-4274-1

Rationale Methods for establishing robust long-term self-administration of intravenous (i.v.) nicotine, the primary psychoactive agent in tobacco, are not well-established in laboratory animals. Objective Here, we examine the use of a fading procedure to establish robust and consistent i.v. nicotine self-administration under second-order schedule conditions in squirrel monkeys. Methods First, self-administration behavior was developed in two groups of male squirrel monkeys using a second-order fixed-interval 5-min schedule with fixed-ratio 5 units (FI 5-min (FR5: S)). Comparable performances were maintained by i.v. cocaine (0.032 mg/kg/injection (inj); group A, n  = 3) and the combination of food delivery (20–30 % condensed milk) and 0.01 mg/kg/inj i.v. nicotine (group B, n  = 3). Subsequently, the concentration of condensed milk was gradually reduced to zero in the second group and self-administration behavior was maintained by i.v. nicotine alone. Next, self-administration of a range of doses of i.v. nicotine (0.001–0.032 mg/kg/inj) and, in additional experiments, the minor tobacco alkaloid anatabine (0.01–0.18 mg/kg/inj) was studied in both groups. Results Results show that nicotine and anatabine had reinforcing effects in both groups. However, optimal doses of nicotine and anatabine maintained significantly higher rates of i.v. self-administration behavior in subjects trained with the fading procedure than in subjects provided with a history of cocaine-maintained responding. Conclusion These results illustrate conditions under which robust i.v. nicotine self-administration can be established in squirrel monkeys and the influence of prior experimental history in the expression of reinforcing effects of nicotine and anatabine.