A recent comprehensive preclinical study provides an excellent example of glutamate’s role in the development and expression of alcohol dependence.123 Griffin and coworkers123 evaluated whether free-choice ethanol access would increase Acb extracellular glutamate levels and found that dependence-induced (chronic intermittent access via ethanol-vapor chambers) ethanol-drinking doubled Acb glutamate levels over those seen in nondependent mice. Moreover, these authors reported that this doubling of glutamate was observed a week later indicating that these increases in glutamate activity were not dependent upon ethanol withdrawal itself. Consistent with prior neuropharmacologic results in studies of low versus high alcohol–consuming inbred mice,120 Griffin etal.123 showed that pharmacologic elevation of glutamate in the Acb, with a pan-glutamate-reuptake inhibitor (Threo-beta-benzyloxyaspartate, TBOA), increased the ethanol intake of nondependent mice to the levels observed in dependent animals, with TBOA also increasing ethanol intake further in the dependent mice. Also consistent with the results of Kapasova and Szumlinski,120 when the mGlu2/3 autoreceptor agonist LY379268 was microinjected into the Acb to lower glutamate levels, ethanol intake was decreased in both the dependent and nondependent mice.123 These latter results parallel earlier work
