1000 [1] % [2,3] [5] DSM- VTA, B844 , DA, ~543 Advances in Psychological Science

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1 ~543 Advances in Psychological Science , DA,, VTA, B [1] % [2,3] [4] 3 1 [5] DSM- [6] * fangxy@bnu.edu.cn 2000 [5] 534

2 nachrs [9] nachrs [7] nachrs mediate [8] Ventral Tegmental Area VTA Nucleus Accumbens NAc Amygdala 1 [10] in vivo microdialysis in vitro electrophysiology Mesolimbic Dopamine System MLSD DA Ach VTA DA NE 5-HT - DA NAc GABA Glutamate

3 prefrontal cortex, PFC [11] VTA DA Rahman Zhang [12] VTA DA Mansvelder [14] 45 5VTA DA 21 challenge dose VTA long-term DA 36 excitation2 VTA GABA VTA DA DA DA VTA desensitization tolerance Yin French [13] DA DA VTA NAc DA VTA nachrs [14] nachrs [9] DA α7 DA VTA PFC [13] NMDA

4 VTA NAcc Mansvelder VTA PFC NAcc DA GABA - Glutamate DA VTA GABA NAc GABA nachrs α7 α4 2 DA Yin French [13] VTA DA GABA GABA DA DA GABA 2 3 [14] GABA nachrs α7 desensitize nachrs α7 α7 nachrs -

5 Mansvelder VTA GABA nachrs [12,14] 3 nachrs NE GABA NE [16,17] DRN 5-HT [18] GABA GABA LTP [19] [20]

6 rcbf U SPECT PET fmri [21] [ 15 O]-H 2 O rcbf rcbf 3.1 rcbf Stain Pankiewicz [5] fmri 3.2 Salokangas Vilkman [22] F 18 [ 18 F]DOPA PET putaman [ 18 F]DOPA 17.3% 30.4% Rose Behm [23] PET [ 15 O]-H 2 O regional Zubieta Heitzeg [24] PET nachrs [21] Cerebral Blood Flow rcbf [25] rcbf rcbf

7 [26] [21] Brody Mandelkern [27] F 18 FDG PET 10 4 Due Huettel [28] fmri [29,30] rare targets 1 [21] fmri fmri [25] 1

8 SPECT (Modell & Mountz, 1995) + FDG PET (Grant et al., 1996) O PET (Childress et al., 1999) fmri (Maas et al., 1998) ++ fmri (Breiter et al., 1997) + - FDG PET (Volkow et al., 1999) C PET (Volkow et al., 1999) + Hommer FDG= O= 11 C= 5 2

9 fmri ERP [7] [1] Guindon G E, Boisclair D. Past, current, and future trends in tobacco use. The World Bank URL: tobacco/publications.asp [2] URL: [3]. URL: / html [4] [5] Stein E A, Pankiewicz J, Harsch H H, Cho J-K, Fuller S A, Hoffmann R G, Hawkins M, Rao S M, Bandettini P A, Bloom A S. Nicotine-induced limbic cortical activation in the human brain: A functional MRI Study. The American Journal of Psychiatry, 1998, 155(8): [6] Diagnostic and Statistical Manual of Mental Disorders (DSM- ). American Psychological Association, , 2000 [8] Blomqvist O, Ericson M, Johnson D, Engel J A, Soederpalm B. Voluntary ethanol intake in the rat: effects of nicotinic acetylcholine receptor blockade or subchronic nicotine treatment. European Journal of Pharmacology, 1996, 314: [9] Paterson D, Nordberg P. Neuronal nicotinic receptors in the human brain. Progress in Neurobiology, 2000, 61: [10]. -., 2003, 12(1): 2 5 [11].., 2002, 11(2): [12] Rahman S, Zhang J, Corrigall, W A. Effects of acute and chronic nicotine on somatodendritic dopamine release of the rat ventral tegmental area: in vivo microdialysis. Neuroscience Letters, 2003, 348: [13] Yin R, French E D. A comparison of the effects of nicotine on dopamine and non-dopamine neurons in the rat ventral tegmental area: An in vitro electrophysiological. Brain Research Bulletin, 2000, 51(6): [14] Mansvelder H D, Keath J R, McGehee D S. Synaptic mechanisms underlie nicotine-induced excitability of brain reward areas. Neuron, 2002, 33: [15] Schilstroem B, Nomikos G G, Nisell M, Hertel P, Svensson T H. N-Methyl- D-aspartate receptor antagonism in the ventral tegmental area diminishes the systemic nicotine-induced dopamine release in the nucleus accumbens. Neuroscience, 1998, 82(3): [16] Leslie F M, Gallardo K A Park M K. Nicotinic acetylcholine receptor- mediated release of [3H] norepinephrine from developing and adult rat hippocampus:

10 direct and indirect mechanisms. Neuropharmacology, 2002, 42: [17] Fu Y, Matta S G, Kane V B, Sharp B M. Norepinephrine release in amygdala of rats during chronic nicotine self-administration: an in vivo microdialysis study. Neuropharmacology 2003, 45: [18] Seth P, Cheeta S, Tucci S, File S E. Nicotinic serotonergic interactions in brain and behaviour. Pharmacology. Biochemistry and Behavior, 2002, 71: [19] Li S P, Park M S, Bahk J Y, Kim M O. Chronic nicotine and smoking exposure decreases GABAB1 receptor expression in the rat hippocampus. Neuroscience Letters, 2002, 334: [20] Qhobosheane M, Wu D, Gu Y, Tan W. A two-dimensional imaging biosensor to monitor enhanced brain glutamate release stimulated by nicotine. Journal of Neuroscience Methods, 2004, 135: [21] Hommer D W. Functional Imaging of Craving. Alcohol Research and Health, 1999, 23(3): [22] Salokangas R K R, Vilkman H, Ilonen T, Taiminen T, Solin O, Alanen A, Syvaelahti E, Hietala J. High levels of dopamine activity in the basal ganglia of cigarette smokers. American Journal of Psychiatry, 2000, 157: [23] Rose J E, Behm F M, Westman E C, Mathew R J, London E D, Hawk T C, Turkington T G, Coleman R E. PET studies of the influences of nicotine on neural systems in cigarette smokers.the American Journal of Psychiatry, 2003, 160(2): [24] Zubieta J-K, Heitzeg M M, Xu R.A.K., Pharm S G, Domino E F. Regional cerebral blood flow responses to smoking in tobacco smokers after overnight abstinence. American Journal of Psychiatry, 2005, 162: [25] Miyata H, Yanagita T. Neurobiological mechanisms of nicotine craving. Alcohol, 2001, 4: [26] Sayette M A, Shiffman S, Tiffany S T, Niaura R S, Martin C S, Shadel W G. The measurement of drug craving, Addiction, 2000, 95, [27] Brody A L, Mandelkern M A, London E D, Childress A R, et al. Brain metabolic changes during cigarette craving. Archives of General psychiatry, 2002, 59(12): [28] Due D L, Huettel S A, Hall W G, Rubin D C. Activation in mesolimbic and visuospatial neural circuits elicited by smoking clues:evidence from functional magnetic resonance imaging. The American Journal of Psychiatry, 2002, 159(6): [29] Schneider F, Habel U, Wagner M, Franke P, et al. Subcortical correlates of craving in recently abstinent alcoholic patients. The American Journal of Psychiatry, 2001, 158(7): [30] Daglish M R C, Weinstein A W, Malizia A L, Wilson S, et al. Changes in regional cerebral blood flow elicited by craving memories in abstinent opiate-dependent subjects. The American Journal of Psychiatr, 2001, 158(10): Neurobiological Mechanism of Nicotine Dependence Deng Linyuan, Fang Xiaoyi Institute of Developmental Psychology, Beijing Normal University, Beijing , China Abstract: Nicotine dependence is the main cause of cigarette addiction, which is characterized by uncontrollable compulsion of nicotine-seeking, impulsive and continuous nicotine in-taking in order to experience euphoria and happiness, and to avoid withdrawal symptoms without nicotine. This article reviewed some research findings of neurobiological mechanism of nicotine dependence from both animal model and human brain imaging study, which revealed that mesolimbic dopamine system is the important neurobiological basis of nicotine dependence. However, previous studies mostly took a static approach, but rarely considered the dynamic process of nicotine dependence; there are also lack of enough evidences of the differences between nicotine dependence and other drugs dependence, which will direct the future studies. Key words: nicotine-dependence, dopamine, mesolimbic-system, ventral-tegmental-area, brain-imaging.