Activation of Glutamate Transporter 1 Attenuates Relapse to Alcohol-Seeking Behavior in Rats

Relapse to alcohol use after prolonged withdrawal periods is a major problem in the treatment of alcohol addiction in humans. Recent preclinical research has focused on identifying long-term neuroadaptive changes and identifying the behavioral, environmental, and neuronal mechanisms underlying drug relapse. By doing so, potential new avenues for relapse prevention may be developed. Current research suggests that changes in glutamatergic neurotransmission may significantly contribute to alcohol relapse and alcohol addiction. Alcohol dependence has been linked specifically to the increased extracellular glutamate levels in key regions of neurocircuits mainly the mesocorticolimbic circuit. Based on the fact that glutamate transporter1 (GLT1) is responsible for the removal of the majority of extracellular glutamate, we hypothesized that the activation of GLT1 by the use of ceftriaxone, a beta-lactam antibiotic, known to elevate GLT1 expression, would attenuate alcohol consumption in alcohol-preferring (P) rats and ultimately prevent relapse to alcohol-seeking behavior. Statistical analyses showed that P rats treated intraperitoneally with ceftriaxone, exhibited a significant reduction in alcohol consumption followed by a period of alcohol deprivation as compared to saline-treated P rats. Preliminary data with Western blot suggests that activation of GLT1 may play a key role in preventing relapse to alcohol-seeking behavior, and ultimately implicate its potential role as a therapeutic-target for treatment of alcohol dependence.