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

Abstract

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.

Keywords: Anatabine; Cocaine; Experimental history; Minor tobacco alkaloid; Nicotine; Nonhuman primates; Self-administration.