Neuroendocrinological and neuropsychological correlates of dopaminergic function in nicotine dependence.
BACKGROUND
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.


OBJECTIVE
To investigate the impact of smoking on dopaminergic function in humans both on a neuroendocrinological and on a neuropsychological level.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Smolka
Michael N
MN
Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, Universität Heidelberg, 68072 Mannheim, Germany. smolka@zi-mannheim.de
Budde
Henning
H
Karow
Anne C
AC
Schmidt
Lutz G
LG
D000328:Adult; D001058:Apomorphine / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D008297:Male; D009042:Motivation; D009483:Neuropsychological Tests; D009538:Nicotine / Q000009:adverse effects / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D012907:Smoking / Q000503:physiopathology / Q000523:psychology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology* / Q000523:psychology; D014029:Tobacco Use Disorder / Q000503:physiopathology* / Q000523:psychology*
D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D019382:Human Growth Hormone; D009538:Nicotine; D001058:Apomorphine