Upregulation of glutamate receptor subtypes during alcohol withdrawal in rats.
OBJECTIVE
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 (B(max)) 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 B(max) 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 B(max) 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 (K(D)) 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.
Haugbøl
Steven Rosenzweig
SR
Department of Psychiatry, University Hospital Rigshospitalet, Copenhagen, Denmark.
Ebert
Bjarke
B
Ulrichsen
Jakob
J
D000435:Alcoholic Intoxication / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage; D008297:Male; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D021122:Protein Subunits / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000096:biosynthesis*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
D021122:Protein Subunits; D017470:Receptors, Glutamate; D000431:Ethanol