李翔,白洁

• 1:昆明理工大学医学院

摘要(Abstract)：

<正>毒品成瘾是一个世界性的难题,有关成瘾机制的研究较多,目前尚未有治疗毒品成瘾的有效途径。尽管世界各国努力减少非法毒品的使用,但毒品使用仍然是一个重要的公共卫生问题〔1〕。成瘾行为是一种额外的超乎寻常的嗜好和习惯性,其核心行为特征是强迫性用药和强迫性觅药行为,与毒品刺激中枢神经系统而造成的兴奋性有关。可卡因具有较强兴奋作用的药物,可与多巴胺转运体结合,从而抑制多巴胺的重摄取,导致大脑内多巴胺浓度增高,从而产生欣快感〔2〕。使用多巴胺能

关键词(KeyWords)： 可卡因;成瘾;多巴胺

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(Nos.81160162,U1202227)

作者(Author): 李翔,白洁

参考文献(References)：

• 1 Cain MA,Bornick P,Whiteman V.The maternal,fetal,and neonatal effects of cocaine exposure in pregnancy〔J〕.Clin Obstet Gynecol,2013;56(1):124-32.
• 2 Dehnes Y,Shan J,Beuming T,et al.Conformational changes in dopamine transporter intracellular regions upon cocaine binding and dopamine translocation〔J〕.Neurochem Int,2014;73(1):4-15.
• 3 Bye A.Experiments with cocaine and heroin addicts-are they predictive〔J〕?Curr Opin Pharmacol,2014;14(1):74-80.
• 4 Kupchik YM,Scofield MD,Rice KC,et al.Cocaine dysregulates opioid gating of GABA neurotransmission in the ventral pallidum〔J〕.J Neurosci,2014;34(3):1057-66.
• 5 Dietz DM,Sun H,Lobo MK,et al.Rac1 is essential in cocaine-induced structural plasticity of nucleus accumbens neurons〔J〕.Nat Neurosci,2012;15(6):891-6.
• 6 Thomas MJ,Kalivas PW,Shaham Y.Neuroplasticity in the mesolimbic dopamine system and cocaine addiction〔J〕.Br J Pharmacol,2008;154(2):327-42.
• 7 Willuhn I,Burgeno LM,Groblewski PA,et al.Excessive cocaine use results from decreased phasic dopamine signaling in the striatum〔J〕.Nat Neurosci,2014;17(5):704-9.
• 8 Bannon MJ,Johnson MM,Michelhaugh SK,et al.A molecular profile of cocaine abuse includes the differential expression of genes that regulate transcription,chromatin,and dopamine cell phenotype〔J〕.Neuropsychopharmacology,2014;39(9):2191-9.
• 9 Renthal W,Kumar A,Xiao G,et al.Genome-wide analysis of chromatin regulation by cocaine reveals a role for sirtuins〔J〕.Neuron,2009;62(3):335-48.
• 10 Nair A,Vaidya VA.Cyclic AMP response element binding protein and brain-derived neurotrophic factor:molecules that modulate our mood〔J〕?J Biosci,2006;31(3):423-34.
• 11 Ferguson SM,Fasano S,Yang P,et al.Knockout of ERK1 enhances cocaine-evoked immediate early gene expression and behavioral plasticity〔J〕.Neuropsychopharmacology,2006;31(12):2660-8.
• 12 Valjent E,Corvol JC,Trzaskos JM,et al.Role of the ERK pathway in psychostimulant-induced locomotor sensitization〔J〕.BMC Neurosci,2006;7(1):20.
• 13 Lu L,Hope BT,Dempsey J,et al.Central amygdala ERK signaling pathway is critical to incubation of cocaine craving〔J〕.Nat Neurosci,2005;8(2):212-9.
• 14 Lu L,Uejima JL,Gray SM,et al.Systemic and central amygdala injections of the m GluR(2/3)agonist LY379268 attenuate the expression of incubation of cocaine craving〔J〕.Biol Psychiatry,2007;61(5):591-8.
• 15 Miszkiel J,Detka J,Cholewa J,et al.The effect of active and passive intravenous cocaine administration on the extracellular signal-regulated kinase(ERK)activity in the rat brain〔J〕.Pharmacol Rep,2014;66(4):630-7.
• 16 Chen R,Tilley MR,Wei H,et al.Abolished cocaine reward in mice with a cocaine-insensitive dopamine transporter〔J〕.Proc Natl Acad Sci USA,2006;103(24):9333-8.
• 17 Chambers RA,Taylor JR,Potenza MN.Developmental neurocircuitry of motivation in adolescence:a critical period of addiction vulnerability〔J〕.Am J Psychiatry,2003;160(6):1041-52.
• 18 Vaughan RA,Foster JD.Mechanisms of dopamine transporter regulation in normal and disease states〔J〕.Trends Pharmacol Sci,2013;34(9):489-96.
• 19 Cagniard B,Sotnikova TD,Gainetdinov RR,et al.The dopamine transporter expression level differentially affects responses to cocaine and amphetamine〔J〕.J Neurogenet,2014;28(1-2):112-21.
• 20 Oleson EB,Talluri S,Childers SR,et al.Dopamine uptake changes associated with cocaine self-administration〔J〕.Neuropsychopharmacology,2009;34(5):1174-84.
• 21 Kosten TA,Zhang XY,Kehoe P.Infant rats with chronic neonatal isolation experience show decreased extracellular serotonin levels in ventral striatum at baseline and in response to cocaine〔J〕.Brain Res Dev Brain Res,2004;152(1):19-24.
• 22 Pierce KL,Premont RT,Lefkowitz RJ.Seven-transmembrane receptors〔J〕.Nat Rev Mol Cell Biol,2002;3(9):639-50.
• 23 Volkow ND,Fowler JS,Wang GJ.The addicted human brain viewed in the light of imaging studies:brain circuits and treatment strategies〔J〕.Neuropharmacology,2004;47(Suppl 1):3-13.
• 24 Mash DC,Pablo J,Ouyang Q,et al.Dopamine transport function is elevated in cocaine users〔J〕.J Neurochem,2002;81(2):292-300.
• 25 Howell LL,Negus SS.Monoamine transporter inhibitors and substrates as treatments for stimulant abuse〔J〕.Adv Pharmacol,2014;69(1):129-76.
• 26 Kustrimovic N,Rasini E,Legnaro M,et al.Expression of dopaminergic receptors on human CD4+T lymphocytes:flow cytometric analysis of naive and memory subsets and relevance for the neuroimmunology of neurodegenerative disease〔J〕.J Neuroimmune Pharmacol,2014;9(3):302-12.
• 27 Xu M,Koeltzow TE,Santiago GT,et al.Dopamine D3 receptor mutant mice exhibit increased behavioral sensitivity to concurrent stimulation of D1 and D2 receptors〔J〕.Neuron,1997;19(4):837-48.
• 28 Hachimine P,Seepersad N,Ananthan S,et al.The novel dopamine D3receptor antagonist,SR 21502,reduces cocaine conditioned place preference in rats〔J〕.Neurosci Lett,2014;569(1):137-41.
• 29 Puig S,Marie N,Benturquia N,et al.Influence of cocaine administration patterns on dopamine receptor regulation〔J〕.Psychopharmacology(Berl),2014;231(16):3131-7.
• 30 Nader MA,Morgan D,Gage HD,et al.PET imaging of dopamine D2 receptors during chronic cocaine self-administration in monkeys〔J〕.Nat Neurosci,2006;9(8):1050-6.
• 31 Sasaki A,Constantinof A,Pan P,et al.Cocaine exposure prior to pregnancy alters the psychomotor response to cocaine and transcriptional regulation of the dopamine D1 receptor in adult male offspring〔J〕.Behav Brain Res,2014;265(1):163-70.
• 32 Edwards S,Whisler KN,Fuller DC,et al.Addiction-related alterations in D1 and D2 dopamine receptor behavioral responses following chronic cocaine self-administration〔J〕.Neuropsychopharmacology,2007;32(2):354-66.
• 33 Mameli M,Halbout B,Creton C,et al.Cocaine-evoked synaptic plasticity:persistence in the VTA triggers adaptations in the NAc〔J〕.Nat Neurosci,2009;12(8):1036-41.
• 34 Miller JS,Barr JL,Harper LJ,et al.The GSK3 signaling pathway is activated by cocaine and is critical for cocaine conditioned reward in mice〔J〕.PLo S One,2014;9(2):e88026
• 35 Covey DP,Roitman MF,Garris PA.Illicit dopamine transients:reconciling actions of abused drugs〔J〕.Trends Neurosci,2014;37(4):200-10.
• 36 Arora D,Hearing M,Haluk DM,et al.Acute cocaine exposure weakens GABA(B)receptor-dependent G-protein-gated inwardly rectifying K+signaling in dopamine neurons of the ventral tegmental area〔J〕.J Neurosci,2011;31(34):12251-7.
• 37 Dixon CI,Halbout B,King SL,et al.Deletion of the GABA alpha2-subunit does not alter self administration of cocaine or reinstatement of cocaine seeking〔J〕.Psychopharmacology(Berl),2014;231(13):2695-703.
• 38 Maguire EP,Macpherson T,Swinny JD,et al.Tonic inhibition of accumbal spiny neurons by extrasynaptic alpha4betadelta GABAA receptors modulates the actions of psychostimulants〔J〕.J Neurosci,2014;34(3):823-38.
• 39 Mombereau C,Lhuillier L,Kaupmann K,et al.GABAB receptor-positive modulation-induced blockade of the rewarding properties of nicotine is associated with a reduction in nucleus accumbens Delta Fos B accumulation〔J〕.J Pharmacol Exp Ther,2007;321(1):172-7.
• 40 Bocklisch C,Pascoli V,Wong JC,et al.Cocaine disinhibits dopamine neurons by potentiation of GABA transmission in the ventral tegmental area〔J〕.Science,2013;341(6153):1521-5.