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Alterations in opiate receptor function after chronic ethanol exposure.

P L Hoffman, S Urwyler, B Tabakoff

    The Journal of Pharmacology and Experimental Therapeutics
    |July 1, 1982
    PubMed
    Summary
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    Chronic ethanol consumption alters how the brain responds to morphine. Withdrawal from ethanol reduces the effectiveness of morphine on dopamine metabolism and changes opiate receptor properties.

    Area of Science:

    • Neuroscience
    • Pharmacology
    • Addiction Research

    Background:

    • Chronic ethanol consumption is known to affect neurotransmitter systems, including dopamine.
    • Opiate receptors play a crucial role in modulating dopamine release in brain regions like the striatum.

    Purpose of the Study:

    • To investigate the impact of chronic ethanol consumption and subsequent withdrawal on morphine's effects on striatal dopamine metabolism.
    • To examine alterations in high-affinity striatal opiate receptor binding and sensitivity following ethanol treatment.

    Main Methods:

    • Mice were chronically administered an ethanol-containing liquid diet.
    • Following a 24-hour withdrawal period, dose-response curves for morphine-induced striatal dopamine metabolism were assessed.
    • Binding affinity of the high-affinity caudate morphine receptor for dihydromorphine was measured, including sensitivity to sodium ions.

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    Main Results:

    • The dose-response curve for morphine-induced dopamine metabolism stimulation was shifted rightward in ethanol-withdrawn mice, indicating reduced sensitivity.
    • The apparent ED50 for morphine increased by 33% in ethanol-treated mice.
    • A decrease in the affinity of the high-affinity caudate morphine receptor for dihydromorphine was observed, along with reduced sodium ion sensitivity.

    Conclusions:

    • Morphine's effects on striatal dopamine metabolism are, in part, mediated by high-affinity dihydromorphine receptors.
    • Ethanol treatment and withdrawal induce specific changes in these opiate receptors, affecting their binding affinity and ion sensitivity.