Alcohol withdrawal reaction as a result of adaptive changes of excitatory amino acid receptors.

Recent electrophysiological and biochemical studies suggest that ethanol interferes with excitatory amino acid (EAA) neurotransmission. Here, we present electrophysiological evidence that, following cessation of a chronic ethanol treatment, noradrenergic locus coeruleus (LC) neurons display hyperactivity at the same time as a specifically enhanced sensitivity to microiontophoretically applied NMDA or quisqualate. Furthermore, after chronic ethanol treatment, but not before, the NMDA receptor antagonist MK 801 (0.3-2.4 mg/kg, i.v.) dose-dependently inhibited the firing of the LC neurons. Our data indicate that an up-regulation of EAA receptors located on LC neurons accounts for the changes in LC firing in ethanol-treated rats. We propose that activation of the LC contributes to the clinical signs of the ethanol abstinence reaction and that EAA antagonists may be beneficial therapeutically for its treatment.