GLUTAMATE LINKED ION CHANNELS DURING ALCOHOL WITHDRAWAL

Project: Research project

Project Details

Description

Alcoholism is a clinical problem that affects millions of people
world-wide. Although various aspects of the disease have been extensively
studied, its molecular and biochemical etiologies are not understood.
Recently, new tools have become available for use in characterizing the
symptomatology of alcoholism, and some potential predisposing factors that
may play a role in the development of the disease and (or) its clinical
course. Mouse lines have been developed for their susceptibility to
seizures during withdrawal from chronic ethanol exposure. Thus, withdrawal
seizure prone (WSP) and resistant (WSR) mice provide a behavioral model for
use in characterizing physiological changes that accompany physical
dependence on alcohol. In addition, molecular and biochemical mechanisms
that predispose WSP mice to symptoms of withdrawal, and protect WSR mice,
can be examined using new radioligands that bind to sites of anticonvulsant
action. Within a three year period, the experiments described in this proposal will
examine the hypothesis that alterations in the excitatory amino acid
receptor - linked ion channel complex in brain precede and accompany
susceptibility to seizures during withdrawal from ethanol. Thus, this
project will characterize: (1) the sensitivity of [3H]glutamate receptors
to glycine and the sensitivity to glutamate and glycine of the associated
ion channel binding site for radiolabelled MK-801, a potent and selective
anticonvulsant agent, in brains from WSP and WSR mice. (2) the effects of
chronic ethanol exposure on each of the above interactions in brain tissue
from WSP and WSR mice, and (3) the effects of withdrawal from ethanol on
the interactions among receptor sites in the glutamic acid receptor linked
- ion channel complex in brain tissue from WSP and WSR mice. The results of these studies could suggest biochemical mechanisms that are
involved in the pathophysiology of symptoms of withdrawal, and indicate new
directions in research for the development of specific pharmacotherapies
that can be used in the treatment of those symptoms.
StatusFinished
Effective start/end date2/1/911/31/95

Funding

  • National Institutes of Health: $98,286.00
  • National Institutes of Health: $103,519.00
  • National Institutes of Health

ASJC

  • Medicine(all)

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