[Recent advances in research on nicotine dependence and reward mechanism].
Tobacco/nicotine dependence involves both psychological and physiologic dependence on nicotine. A recent summary of the clinical aspects of nicotine dependence disorders is provided in the ICD-10 of the WHO. There is growing evidence suggesting that nicotine depends on dopamine (DA) for its reinforcing effects. Suppression of DA function using DA-receptor antagonist affects the intravenous self-administration of nicotine, the discriminative properties of nicotine, nicotine-induced intracranial self-stimulation and nicotine-conditioned place preference. The increase inextracellular DA in the nucleus accumbens (NAcc) is a major factor that mediates the self-administration of nicotine. Recently, alpha 7-nicotinic receptors in the ventral tegmental area (VTA) contribute to the acute effects of nicotine on the mesolymbic DA system, reinforcing effects of nicotine and withdrawal symptoms from nicotine. The action of glutamate (Glu) at N-methyl-D-aspartate (NMDA)-sensitive receptors within the VTA is required for nicotine to stimulate DA release in the NAcc. Molecular epidemiological studies have shown that smoking behavior is more strongly influenced by a combination of the serotonin transporter gene and the neuroticism than by either factor alone. Clinically, bupropion, an antidepressant, has been licensed for use in USA to help patients stop smoking. The underlying mechanism is thought to be mediated by increasing the concentration of DA in the NAcc.
Department of Psychiatry, Saint Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki 216-8511, Japan. miyasato@marianna-u.ac.jp
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D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism; D016642:Bupropion / Q000627:therapeutic use; D004298:Dopamine / Q000502:physiology; D005973:Glutamine / Q000502:physiology; D006801:Humans; D016202:N-Methylaspartate / Q000502:physiology; D011978:Receptors, Nicotinic / Q000502:physiology; D012054:Reinforcement, Psychology; D014029:Tobacco Use Disorder / Q000188:drug therapy / Q000209:etiology
D000928:Antidepressive Agents; D011978:Receptors, Nicotinic; D016642:Bupropion; D005973:Glutamine; D016202:N-Methylaspartate; D004298:Dopamine