Neuroendocrinological and neuropsychological correlates of dopaminergic function in nicotine dependence.

Abstract

There is multiple evidence that nicotine--as with ethanol and other drugs of abuse--stimulates dopamine release in the ventral striatum as a central part of the brain reward circuits. Chronic nicotine exposure leads to changes in these dopaminergic reward circuits. During nicotine withdrawal, an impaired dopaminergic function has been reported. On the behavioral level, this seems to result in motivational disturbances in abstaining smokers. To investigate the impact of smoking on dopaminergic function in humans both on a neuroendocrinological and on a neuropsychological level. Thirty-seven healthy smokers were assessed whilst smoking (test 1) and after abstaining overnight for 12 h (test 2). A control group of 18 non-smokers was also examined twice. Severity of nicotine dependence, incentive motivation, digit span and verbal fluency were assessed. The sensitivity of central dopamine (DA) D2 receptors was assessed with the apomorphine-induced growth hormone (GH) secretion. ANOVA revealed that GH response was significantly lower in smokers than in non-smokers (P=0.04). The GH response was significantly inversely correlated with severity of nicotine dependence (r=-0.39). Neuropsychological performance was not influenced by smoking status. After overnight abstinence from nicotine GH response, digit span and verbal fluency were not affected, whereas incentive motivation was significantly impaired in smokers (P=0.04). Smoking is significantly associated with a reduced sensitivity of central DA D2 receptors. This alteration of dopaminergic sensitivity is stable even after 12 h of abstinence from nicotine. Therefore, the hypothesis that the motivational impairment during withdrawal from nicotine is associated with an altered sensitivity of central DA D2 receptors cannot be supported.