Fig. 3.

Preclinical examples of glutamate-based approaches to therapeutically targeting various elements of alcoholism. Potentiating alcohol intoxication: mice administered the NMDAR antagonist, MK-801, show markedly prolonged sedative/hypnotic responses to ethanol (Palachick et al. 2008). Alleviating alcohol withdrawal: rats infused with the AMPAR antagonist DNQX directly into amygdala exhibited less ethanol-induced withdrawal anxiety (Lack et al. 2007). Blunting alcohol craving: mice with deletion of the NMDAR anchoring protein PSD-95 consumed less ethanol at baseline and after deprivation (Camp et al. 2011). Reducing alcohol-seeking and consumption: mice with deletion of the NMDAR anchoring protein PSD-95 consumed less ethanol at baseline and after deprivation (Camp et al. 2011). Blunting alcohol craving: rats administered the mGluR5 antagonist, MPEP, reduced ethanol-seeking (black bars active lever presses) during cue-induced reinstatement (Cowen et al. 2003). Preventing habitual and compulsive alcohol consumption: rats administered the GlyT1 transporter blocker, Org25935, decreased “compulsive-like” alcohol consumption after a history of chronic ethanol treatment/deprivation (Vengeliene et al. 2010). Arresting alcohol-induced neurodegeneration: rats treated with the mGluR2/3 agonist, LY379268, were protected against binge ethanol-induced increased in TGF-β2-immunoreactivity, a measure of neurodegeneration. Adapted from Cippitelli et al. 2010