Behavioral Analysis of Nicotine Self‐Administration

Abstract

Despite the high prevalence of nicotine use in humans, robust nicotine self‐administration has been difficult to demonstrate in laboratory animals. We conducted a parametric analysis of nicotine self‐administration in non‐human primates to better understand the conditions that support nicotine intake. Adult rhesus monkeys (N=6) were trained to self‐administer intravenous nicotine (0.01 mg/kg) under a fixed ratio (FR) 1 schedule of reinforcement during daily 90 min sessions. After self‐administration of vehicle and a range of nicotine doses (0.001‐0.1 mg/kg) was evaluated, the dose was returned to 0.01 mg/kg nicotine and the FR was increased across multiple sessions in an ascending order (i.e. 1, 3, 6, 10, 18, 30, 60, 100, etc). To compare nicotine self‐administration with that of another stimulant, monkeys were subsequently given access to 0.01 mg/kg cocaine using identical testing procedures. Finally, the effects of FR change on other doses of nicotine (0.0032 and 0.032 mg/kg) were assessed. Results indicate that nicotine self‐administration followed an inverted‐U pattern with the peak injections per session at 0.0032 mg/kg. Self‐administration of nicotine (at each dose) and cocaine gradually decreased as the fixed ratio size was increased. Application of the exponential model of demand to the FR data found that essential value for cocaine was significantly higher than that for nicotine. Interestingly, elasticity of demand differed according to nicotine dose with the order: 0.0032 < 0.01 < 0.032 mg/kg/inj. These data show that high levels of nicotine self‐administration can be achieved in non‐human primates but that it's reinforcing strength is limited. Supported by NIH DA026892.