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Alcohol and Alcoholism Advance Access published online on November 29, 2004
Alcohol and Alcoholism, doi:10.1093/alcalc/agh117
© 2004 by Medical Council on Alcohol
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Received May 30, 2004
Revised September 19, 2004
Accepted September 19, 2004

Article

UPREGULATION OF GLUTAMATE RECEPTOR SUBTYPES DURING ALCOHOL WITHDRAWAL IN RATS

STEVEN ROSENZWEIG HAUGBØL 1, BJARKE EBERT 2, and JAKOB ULRICHSEN 1*

1 Neuropsychiatric Research Group, Department of Psychiatry 6234, University Hospital Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
2 Department of Neurobiology, Biological Research, Lundbeck A/S, Ottiliavej 9, DK 2500 Valby, Denmark

* To whom correspondence should be addressed.
JAKOB ULRICHSEN, E-mail: jakob.ulrichsen{at}mail.dk


  Abstract

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-4-isoxazolepropionic acid (AMPA) receptors were studied in membranes from the forebrain by using the specific ligands [3H]MK-801 and [3H]AMPA, respectively. Results: Although no change in the maximal density (Bmax) of [3H]MK-801 binding sites was observed at the time of withdrawal, [3H]MK-801 binding was increased by 49% 12 h into the withdrawal reaction compared with the control group. At 36 h post alcohol the Bmax of the [3H]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 Bmax of the [3H]AMPA binding was detected, but 12 h into the withdrawal reaction the [3H]AMPA binding was markedly increased by 94%. At 36 h post alcohol the [3H]AMPA binding had returned to control levels. No significant alterations in the dissociation constant (KD) of either [3H]MK-801 or [3H]AMPA binding was observed at any time point. Conclusions: NMDA and AMPA receptors are involved in the cerebral hyperactivity of alcohol withdrawal.


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