Chronic exposure to EtOH, whether by forced administration or ingestion, generally enhances the function of NMDARs, most often those containing the NR2B subunit. Increases in glutamate release and responses to some other glutamate receptors are also observed following chronic exposure. The net effect of these increases in glutamatergic transmission appears to be a hyperexcitable CNS state during withdrawal that contributes to withdrawal symptoms and relapse. Excitotoxicity might be another result of this hyper-glutamatergic state. In general, acute EtOH effects on glutamate receptor function and glutamatergic transmission are intact even after subchronic or chronic EtOH exposure, suggesting that behavioral tolerance is not a simple function of loss of pharmacological effects at these synapses. At GABAergic synapses, chronic EtOH generally alters either the efficacy of inhibitory synaptic transmission or the types of receptors involved in transmission. Extrasynaptic GABAA receptor-mediated synaptic responses are also altered, leading to changes in tonic current in the postsynaptic neuron. The pattern of chronic EtOH effects on GABAergic transmission varies considerably across brain regions, making this subject a rich and important area for future investigation. The resultant alterations
