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Alcohol and Alcoholism Advance Access originally published online on November 29, 2004
Alcohol and Alcoholism 2005 40(2):89-95; doi:10.1093/alcalc/agh117
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Alcohol & Alcoholism Vol. 40, No. 2 © Medical Council on Alcohol 2005; all rights reserved

UPREGULATION OF GLUTAMATE RECEPTOR SUBTYPES DURING ALCOHOL WITHDRAWAL IN RATS

STEVEN ROSENZWEIG HAUGBØL1, BJARKE EBERT2 and JAKOB ULRICHSEN1,*

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

* Author to whom correspondence should be addressed at: Department of Psychiatry, Gentofte University Hospital, Niels Andersens Vej 65, DK-2900, Hellerup, Denmark. Tel.: +45 3977 3658; Fax: +45 3977 7600; E-mail: jakob.ulrichsen{at}mail.dk

(Received 30 May 2004; first review notified 11 August 2004; in revised form 19 September 2004; accepted 19 September 2004)

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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