Glutamate Transporter 1: Target for the Treatment of Alcohol Dependence
Authors: Rao, P.S.S.; Sari, Y.
Source: Current Medicinal Chemistry, Volume 19, Number 30, October 2012 , pp. 5148-5156(9)
Publisher: Bentham Science Publishers
Abstract:Emerging evidence indicates that many aspects of alcohol and drug dependence involve changes in glutamate transmission. A number of studies have reported that drugs of abuse, including alcohol and cocaine, alter glutamate transport. Extracellular glutamate is regulated by a number of glutamate transporters in various brain regions. Of these transporters, glutamate transporter (GLT1) is a key player in the removal of most of the extracellular glutamate. Similar to neurodegenerative disease models, in which there is dysfunction of the glutamatergic excitatory system, the role of GLT1 has been tested in drug dependence models that show dysfunction of glutamate transmission. We and others have recently found that ceftriaxone, an FDA-approved drug known to elevate GLT1 expression, attenuates cue-induced cocaine relapse. Moreover, we recently found that alcohol-preferring rats treated with ceftriaxone showed a significant dosedependent reduction in alcohol consumption. We also demonstrated that ceftriaxone-induced upregulation of GLT1 expression was associated with increases in glutamate uptake in Huntington's disease mouse model. Importantly, ceftriaxone is currently in clinical trials for the treatment of amyotrophic lateral sclerosis. This review provides information about the potential therapeutic role of GLT1 for the treatment of alcohol abuse and dependence.
Keywords: EAAT1; EAAT2; GLAST; GLT1; alcohol addiction; alcohol dependence; alcoholpreferring rats; basal extracellular glutamate; cocaine; cystine-glutamate exchanger; glutamate; glutamate transporters; glutamate uptake; nucleus accumbens; prefrontal cortex
Document Type: Research Article
Publication date: October 1, 2012
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