: R964 : A : (Methamphetamine, MA), (Amphetamine-type Stimuants, ATS) , MA ATS, , (VTA), (NAc), (DR),,

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1 25 3, Vol.25 No.3, July 2012 JOURNAL OF NINGBO UNIVERSITY ( NSEE ) 1, 2* 1., ; 2., :,,,. : ; ; ; : R964 : A : (Methamphetamine, MA), (Amphetamine-type Stimuants, ATS) , MA ATS,, 2l. :, 25.,.,,,., 5- [1] [2] [3-5] [6-7],.. 1, (VTA), (NAc), (Amy), (OT), (PFC) (Hip).. NAc (DA), (DAT) DA ;,, DAT, DA, DA, NAc DA., DA, DA DA, DA, DA, DA [8],,,,. 2 7 (72GM) G. 5 (DR),, D 1 D 2 D 1 D 1 D 5,, ; D 2 D 2 D 3 D 4,, : U , ; 2012BAI01B ,,, /, :. misssqunchen@sina.com * 1966,,, /, :. whzhou@vip.163.com

2 3, : 63, D 2,. D 1 D 2,,,,.,, D 1 D D 1 D 2 D 1 D 2., D 1, D 2. ( ). D 1 SCH23390 D 2, MA D 1 [9]. MA, D 1 SCH MA, D 2, MA D 1,, [10]. mpfc D 1 SCH 23390, MA, SCH HT(2C), SCH MA 5-HT(2C). 5-HT(2C) RS SCH 23390, SCH 23390, RS , mpfc D 1 MA [11]., GBR MA, MA, D 1 SKF SKF D 2 PHNO MA. D 1 SCH D 2 D 1 SKF77434 D 2 SDZ SDZ MA [12]. D 1 D 2 MA, D 1 (D 1 KO) D 2 (D 2 KO) MA, D 2 KO, D 1 KO,. : 27 ; D 1 KO 7 ; D 2 KO 4. D 2 MA [13]. D 1 SCH23390 MA D 1 [14]. 2.2 D 3, D 3 D 3. (D 3 RKO), [15], MA 2 mg kg -l (WT) (CPP), D 3 RKO CPP ; CPP ; 5 mg kg -1 MA WT D 3 RKO CPP,, WT, D 3 RKO. MA D 3 RKO CPP, D 3.,,,, ;,, ( ), 2. ( ), ( ),. D 3 CJB090 1(FR1). D 3 PG01037 [16]., D 3 PG01037 B A NGB 2904, D 3

3 BP-897, MA [17-18]. 2.3 DA D 4, D 4, D 4, D 4, [19-20]. D 5 MA. 3, DA,. Ⅱ (VMAT-2) DA, DA. DAT, Na + /Cl -, DA, DA [21-22]. DAT,, DAT,, [23]. DAT AM2517 MA, 2.5 [24]. MA, DAT,., DAT, DAT DAT, D 2 MA DAT [25]., 6- ( )., D 2 VMAT-2 (GFAP). D 2 MA, [8,26]. DAT,, [27]. GZ-793A VMAT2 DAT,, GZ-793A MA CPP [28-29]. MA (TAAR1) DAT, TAAR1 MA DAT, H89 (Ro )., DAT [30]. 4. VTA PFC, NAc., (MD) (BLA),,, 40 γ- (GABA) [31]. VTA..,.,. mglur α- -4- MA, mglur DA, I mglur II mglur MA DA [32]. mglur 5 MTEP [2]. MA [33],, MA. 5,,.,

4 3, : 65,. DAT, MA. MA, MA. : [1] Takamatsu Y, Yamamoto H, Hagino Y, et al. The selective serotonin reuptake inhibitor paroxetine, but not fluvoxamine, decreases methamphetamine conditioned place preference in mice[j]. Curr Neuropharmacol, 2011, 9(1): [2] Gass J T, Osborne M P, Watson N L, et al. mglur5 antagonism attenuates methamphetamine reinforcement and prevents reinstatement of methamphetamine-seeking behavior in rats[j]. Neuropsychopharmacology, 2009, 34(4): [3] Neugebauer N M, Harrod S B, Bardo M T. Nicotine elicits methamphetamine-seeking in rats previously administered nicotine[j]. Drug Alcohol Depend, 2010, 106(1): [4] Glick S D, Sell E M, Maisonneuve I M. Brain regions mediating alpha3beta4 nicotinic antagonist effects of 18- MC on methamphetamine and sucrose self-administration [J]. Eur J Pharmacol, 2008, 599(1-3): [5] Hiranita T, Nawata Y, Sakimura K, et al. Suppression of methamphetamine-seeking behavior by nicotinic agonists [J]. Proc Natl Acad Sci USA, 2006, 103(22): [6] Munzar P, Tanda G, Justinova Z, et al. Histamine h3 receptor antagonists potentiate methamphetamine selfadministration and methamphetamine-induced accumbal dopamine release[j]. Neuropsychopharmacology, 2004, 29(4): [7] Takino N, Sakurai E, Kuramasu A, et al. Roles of the histaminergic neurotransmission on methamphetamineinduced locomotor sensitization and reward: A study of receptors gene knockout mice[j]. Int Rev Neurobiol, 2009, 85: [8] Krasnova I N, Justinova Z, Ladenheim B, et al. Methamphetamine self-administration is associated with persistent biochemical alterations in striatal and cortical dopaminergic terminals in the rat[eb/ol]. [ ]. ournal.pone [9] Brennan K A, Carati C, Lea R A, et al. Effect of D1-like and D 2 -like receptor antagonists on methamphetamine and 3,4-methylenedioxymethamphetamine self-administration in rats[j]. Behav Pharmacol, 2009, 20(8): [10] Carati C, Schenk S. Role of dopamine D 1 - and D 2 -like receptor mechanisms in drug-seeking following methamphetamine self-administration in rats[j]. Pharmacol Biochem Behav, 2011, 98(3): [11] Hall D A, Powers J P, Gulley J M. Blockade of D 1 dopamine receptors in the medial prefrontal cortex attenuates amphetamine- and methamphetamine-induced locomotor activity in the rat[j]. Brain Res, 2009, 1300: [12] Tidey J W, Bergman J. Drug discrimination in methamphetamine-trained monkeys: Agonist and antagonist effects of dopaminergic drugs[j]. J Pharmacol Exp Ther, 1998, 285(3): [13] Ito M, Numachi Y, Ohara A, et al. Hyperthermic and lethal effects of methamphetamine: Roles of dopamine D 1 and D 2 receptors[j]. Neurosci Lett, 2008, 438(3): [14] Jayanthi S, McCoy M T, Beauvais G, et al. Methamphetamine induces dopamine D 1 receptordependent endoplasmic reticulum stress-related molecular events in the rat striatum[eb/ol]. [ ]. plosone.org/article/info%3adoi%2f %2fjournal.pon e [15],,,. D 3 [J]., 2009, 18(3): [16] Orio L, Wee S, Newman A H, et al. The dopamine D 3 receptor partial agonist CJB090 and antagonist PG01037 decrease progressive ratio responding for methamphetamine in rats with extended-access[j]. Addict Biol, 2010, 15(3): [17] Higley A E, Spiller K, Grundt P, et al. PG01037, a novel dopamine D 3 receptor antagonist, inhibits the effects of methamphetamine in rats[j]. J Psychopharmacol, 2011, 25(2): [18] Spiller K, Xi Z X, Peng X Q, et al. The selective dopamine D 3 receptor antagonists SB A and NGB 2904 and the putative partial D 3 receptor agonist BP-897 attenuate methamphetamine-enhanced brain stimulation reward in rats[j]. Psychopharmacology (Berl), 2008, 196(4): [19] Kruzich P J, Suchland K L, Grandy D K. Dopamine D 4

5 receptor-deficient mice, congenic on the C57BL/6J background, are hypersensitive to amphetamine[j]. Synapse, 2004, 53(2): [20] Rubinstein M, Phillips T J, Bunzow J R, et al. Mice lacking dopamine D 4 receptors are supersensitive to ethanol, cocaine, and methamphetamine[j]. Cell, 1997, 90(6): [21] Fleckenstein A E, Volz T, Riddle E L, et al. New insight into the mechanism of action of amphetamine[j]. J Pharmacol Sci, 2003, 92(3): [22] Vol T J, Hanson G R, Fleckenstein A E. The role of the plasmalemmal dopamine and vesicular momoamine transporters in methamphetamine-induced popaminergic deficits[j]. Neurochem, 2007, 101(4): [23] Tiller M R, Cagniard B, Zhuang X, et a1 Cocaine reward and locomotion stimulation in mice with reduced dopamine transporter expression[j]. BMC Neurosci, 2007, 8:42. [24] Czoty P W, Makriyannis A, Bergman J. Methamphetamine discrimination and in vivo micro- dialysis in squirrel monkeys[j]. Psychopharmacology (Berl), 2004, 175(2): [25] Hadlock G C, Baucum A J, King J L, et al. Mechanisms underlying methamphetamine-induced dopamine transporter complex formation[j]. J Pharmacol Exp Ther, 2009, 329(1): [26] Hadlock G C, Chu P W, Walters E T, et al. Methamphetamine-induced dopamine transporter complex formation and dopaminergic deficits: the role of D 2 receptor activation[j]. J Pharmacol Exp Ther, 2010, 335(1): [27] Harrod S B, Dwoskin L P, Crooks P A, et al. Lobeline attenuates d-methamphetamine self-administration in rats [J]. J Pharmacol Exp Ther, 2001, 298(1): [28] Beckmann J S, Denehy E D, Zheng G, et al. The effect of a novel VMAT2 inhibitor, GZ-793A, on methamphetamine reward in rats[j]. Psychopharmacology (Berl), 2012, 220(2): [29] Neugebauer N M, Harrod S B, Stairs D J, et al. Lobelane decreases methamphetamine self-administration in rats [J]. Eur J Pharmacol, 2007, 571(1): [30] Xie Z, Miller G M. A receptor mechanism for methamphetamine action in dopamine transporter regulation in brain[j]. J Pharmacol Exp, 2009, 330(1): [31],. [J]., 2003, 31(2): [32] Shimazoe T, Doi Y, Arai I, et al. Both metabotropic glutamate I and II receptors mediate augmentation of dopamine release from the striatum in methamphetaminesensitized rats[j]. Jpn J Pharmacol, 2002, 89(1): [33] Hiranita T, Nawata Y, Sakimura K, et al. Suppression of methamphetamine-seeking behavior by nicotinic agonists [J]. Proc Natl Acad Sci USA, 2006, 103(22): Methamphetamine Dependence and Mesocorticolimbic Dopaminergic System CHEN Qun 1, ZHOU Wen-hua 2* ( 1.Ningbo College of Health Sciences, Ningbo , China; 2.Medical School, Ningbo University, Ningbo , China ) Abstract: As one of the amphetamine type stimulants, methamphetamine has been abused widely in China. The methamphetamine dependence is related to the mesocorticolimbic dopaminergic system. This paper describes the mechanisms underlying methamphetamine dependence on the dopamine release, dopamine receptors and dopamine transporter. Key words: methamphetamine; mesocorticolimbic dopaminergic system; dopamine receptor; dopamine transporter

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