ROLE OF LIGAND-GATED ION CHANNELS IN EHTANOL DISCRIMINAT

    Project: Research project

    Project Details

    Description

    The aim of the research project is to assess the contribution of specific
    ligand-gated ion channels in mediating the perceptible effects of ethanol
    in the CNS. Three of these receptor/channel complexes that are
    particularly sensitive to the effects of ethanol in in vitro assays are the
    GABAA receptor complex, the NMDA subtype of glutamate receptor complex, and
    the 5-HT3 subtype of serotonin receptor. These receptor systems encompass
    components of the major inhibitory and excitatory neurotransmitter systems,
    and a component of the serotonin system, implicated in many behavioral
    effects of ethanol. The interaction of ethanol with these receptor systems
    in electrophysiological and biochemical assays occurs at concentrations of
    5-50 mM, corresponding to a range of blood ethanol concentrations
    associated with mild intoxication to loss of righting reflex. The
    sensitivity of these receptor-linked ion channels to ethanol indicates a
    specificity to the pharmacological actions of ethanol. The interaction of
    ethanol at several different receptor systems can be expected to give rise
    to a mixture of internal stimulus effects, composed of distinguishable
    component parts. Understanding how ethanol acts at each component receptor
    system to produce its discriminable effects will advance our understanding
    of ethanol's pharmacological actions and may be helpful in the design of
    potential pharmacotherapies to alter and possibly limit excessive ethanol
    intake. The proposed studies utilize the drug discrimination procedure to 1)
    determine the modulatory sites on the GABAA receptor complex that are
    sufficient to produce ethanol-like discriminative effects 2) determine if
    antagonism of NMDA transmission by compounds acting at the NMDA, channel,
    glycine or polyamine modulatory sites on the NMDA receptor complex results
    in similar discriminative stimulus effects as ethanol. 3) Determine the
    structural requirements of the 5-HT3 antagonists to block the
    discriminative effects of ethanol, and if this blockade can be due to
    action of the 5-HT3 antagonists at the nicotinic cholinergic or GABAA
    channels. 4) Determine if the dose of ethanol used in training the
    discrimination determines the relative contribution of each receptor system
    in mediating the discriminative effects of ethanol. 5) Whether a component
    of the compound discriminative stimulus effects of ethanol can be isolated
    from the action of ethanol at other receptor systems.
    StatusFinished
    Effective start/end date7/1/926/30/03

    Funding

    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health: $117,791.00
    • National Institutes of Health
    • National Institutes of Health: $172,264.00
    • National Institutes of Health: $174,552.00
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health: $177,431.00

    ASJC

    • Medicine(all)

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