Aims: To investigate glutamate receptor subtypes during alcohol withdrawal. Methods: Rats were exposed to severe alcohol intoxication for 84 h and then decapitated at 0, 12 and 36 h after the last alcohol dose (n = 7 per group). Alcohol was administered five times a day by intragastric intubation. The densities of N-methyl-D-aspartate (NMDA) and 2-amino-3-hydroxy-5-methyl-4isoxazolepropionic acid (AMPA) receptors were studied in membranes from the forebrain by using the specific ligands [ 3

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... -801 and [ 3 H]AMPA, respectively. Results: Although no change in the maximal density (B max ) of [ 3 H]MK-801 binding sites was observed at the time of withdrawal, [ 3 H]MK-801 binding was increased by 49% 12 h into the withdrawal reaction compared with the control group. At 36 h post alcohol the B max of the [ 3 H]MK-801 binding was still increased by 24% compared with the control group; however, this difference was not statistically significant. When investigated at the time of withdrawal from chronic alcohol intoxication, no significant alterations in the B max of the [ 3 H]AMPA binding was detected, but 12 h into the withdrawal reaction the [ 3 H]AMPA binding was markedly increased by 94%. At 36 h post alcohol the [ 3 H]AMPA binding had returned to control levels. No significant alterations in the dissociation constant (K D ) of either [ 3 H]MK-801 or [ 3 H]AMPA binding was observed at any time point. Conclusions: NMDA and AMPA receptors are involved in the cerebral hyperactivity of alcohol withdrawal.