GroupⅢmetabotropic glutamate receptors and drug addiction  

作　　者：Limin Mao Minglei Guo Daozhong Jin Bing Xue John Q.Wang 

机构地区：[1]Department of Basic Medical Science,School of Medicine,University of Missouri-Kansas City,Kansas City,MO 64108,USA

出　　处：《Frontiers of Medicine》2013年第4期445-451,共7页医学前沿（英文版）

基　　金：supported by NIH R01 DA010355,R01 MH061469.

摘　　要：Neuroadaptations of glutamatergic transmission in the limbic reward circuitry are linked to persistent drug addiction.Accumulating data have demonstrated roles of ionotropic glutamate receptors and groupⅠandⅡmetabotropic glutamate receptors(mGluRs)in this event.Emerging evidence also identifies Gαi/o-coupled groupⅢmGluRs(mGluR4/7/8 subtypes enriched in the limbic system)as direct substrates of drugs of abuse and active regulators of drug action.Auto-and heteroreceptors of mGluR4/7/8 reside predominantly on nerve terminals of glutamatergic corticostriatal and GABAergic striatopallidal pathways,respectively.These presynaptic receptors regulate basal and/or phasic release of respective transmitters to maintain basal ganglia homeostasis.In response to operant administration of common addictive drugs,such as psychostimulants(cocaine and amphetamine),alcohol and opiates,limbic groupⅢmGluRs undergo drastic adaptations to contribute to the enduring remodeling of excitatory synapses and to usually suppress drug seeking behavior.As a result,a loss-of-function mutation(knockout)of individual groupⅢreceptor subtypes often promotes drug seeking.This review summarizes the data from recent studies on three groupⅢreceptor subtypes(mGluR4/7/8)expressed in the basal ganglia and analyzes their roles in the regulation of dopamine and glutamate signaling in the striatum and their participation in the addictive properties of three major classes of drugs(psychostimulants,alcohol,and opiates).

关 键 词：groupⅢmetabotropic glutamate receptors COCAINE AMPHETAMINE ALCOHOL OPIATE 

分 类 号：R33[医药卫生—人体生理学]