A pharmacological analysis of stimulant-induced increases in smoking.

RATIONALE: Stimulants increase tobacco smoking in healthy adults under controlled laboratory conditions. The mechanisms that mediate stimulant-induced increases in smoking are not known. OBJECTIVE: The purpose of the present experiment was to characterize the pharmacological specificity of stimulant-induced increases in smoking. We tested the effects of methylphenidate and atomoxetine on smoking behavior. Atomoxetine is a norepinephrine transport inhibitor that does not increase dopamine levels in the nucleus accumbens or striatum. If stimulant-induced increases in smoking result from an additive or synergistic effect of these drugs and nicotine on dopamine levels in the nucleus accumbens or striatum, methylphenidate but not atomoxetine should increase smoking. MATERIALS AND METHODS: Doses of methylphenidate (10, 20, and 40 mg) and atomoxetine (20, 40, and 80 mg) were tested once while placebo was tested twice in 12 cigarette smokers. One hour after ingesting drug, participants smoked ad libitum for 4 h. Measures of smoking included total cigarettes, total puffs, and carbon monoxide levels. Snacks and decaffeinated drinks were available ad libitum, and food intake was calculated. RESULTS: Methylphenidate but not atomoxetine dose-dependently increased the number of cigarettes, puffs, and carbon monoxide levels. Methylphenidate and atomoxetine decreased food intake. CONCLUSIONS: The results of this experiment are consistent with the notion that stimulant-induced increases in smoking may result from an additive or synergistic effect of these drugs and nicotine on dopamine levels in the nucleus accumbens or striatum. Additional research is needed to more fully understand the pharmacological mechanisms that mediate the relationship between stimulant use and smoking.