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Related Experiment Videos

Brain noradrenergic systems as a prerequisite for developing tolerance to barbiturates.

B Tabakoff, J Yanai, R F Ritzmann

    Science (New York, N.Y.)
    |April 28, 1978
    PubMed
    Summary

    Mice lacking norepinephrine due to 6-hydroxydopamine treatment did not develop tolerance to phenobarbital

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    Area of Science:

    • Neuropharmacology
    • Neuroscience
    • Drug Tolerance

    Background:

    • Barbiturate tolerance is a common phenomenon.
    • The neurochemical mechanisms underlying barbiturate tolerance are not fully understood.
    • Noradrenergic pathways are implicated in various drug effects.

    Purpose of the Study:

    • To investigate the role of brain norepinephrine in the development of functional tolerance to phenobarbital.
    • To determine if noradrenergic system integrity is essential for barbiturate tolerance.

    Main Methods:

    • Mice were treated with 6-hydroxydopamine to deplete brain norepinephrine.
    • Following treatment, mice were chronically administered phenobarbital.
    • Tolerance was assessed by measuring the duration of loss of righting reflex and hypothermia.

    Main Results:

    • 6-hydroxydopamine treatment significantly depleted brain norepinephrine levels.
    • Mice treated with 6-hydroxydopamine did not develop functional tolerance to phenobarbital.
    • Brain dopamine levels remained largely unaffected by 6-hydroxydopamine treatment.

    Conclusions:

    • Intact brain noradrenergic systems are necessary for the development of tolerance to the hypnotic and hypothermic effects of barbiturates.
    • Norepinephrine depletion prevents functional tolerance to phenobarbital.
    • This suggests a critical role for noradrenergic neurotransmission in drug tolerance.

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