Amphetamine alters glutamate transporter function

Brown University, Providence RI

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Abstract

Drug addiction is a neurological disease that is both deadly and costly. Repeated exposure to drugs result in persistent molecular and cellular changes that alter the physiology neurons in the mesocorticolimbic system. Identification of the initial drug-induced changes may aid in developing effective treatments for drug addiction. The VTA is the site for amphetamine sensitization. Amphetamine treatment acutely increases extracellular levels of dopamine and glutamate in the VTA. The increased levels of extracellular glutamate may be an initial instructive change that promotes sensitization. Levels of extracellular glutamate are maintained by glutamate transporters. Inhibitors of glutamate transport blocks the increase in extracellular glutamate. This proposal seeks to elucidate the molecular mechanisms for the modification of the glutamate transporter function by addressing the following specific aims: Specific Aim 1: To determine whether amphetamine alters glutamate transporter function by impairing glutamate uptake or promoting glutamate efflux. Specific Aim 2: To determine if dopamine mediates the modification of glutamate transporter function. Specific Aim 3: To determine if the modification of glutamate transporter function by amphetamine is persistent.