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Decrease in rat striatal acetylcholine levels by some direct- and indirect-acting dopaminergic antagonists.

S Consolo, H Ladinsky, S Bianchi

    European Journal of Pharmacology
    |September 1, 1975
    PubMed
    Summary
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    Dopamine receptor antagonists like haloperidol and pimozide significantly reduce striatal acetylcholine levels in rats by blocking dopamine receptors. This research clarifies the mechanism of action for several dopamine antagonists.

    Area of Science:

    • Neuropharmacology
    • Neurochemistry

    Background:

    • Dopamine receptor antagonists are known to affect acetylcholine levels.
    • The specific mechanisms and regional effects of these antagonists require further elucidation.

    Purpose of the Study:

    • To investigate the effects of various dopamine receptor antagonists on rat striatal acetylcholine levels.
    • To differentiate between direct and indirect mechanisms of action.

    Main Methods:

    • Administration of dopamine receptor antagonists (pimozide, haloperidol, reserpine, clozapine, fenfluramine) and a dopamine agonist (apomorphine) to rats.
    • Measurement of acetylcholine levels in different brain regions.
    • Assay of striatal choline acetyltransferase and cholinesterase activity.

    Main Results:

    Related Experiment Videos

    • Pimozide, haloperidol, and reserpine decreased striatal acetylcholine by up to 50%.
    • Haloperidol and pimozide's effects were striatum-specific and blocked apomorphine-induced increases, without altering enzyme activity.
    • Clozapine and fenfluramine showed weaker effects, suggesting reversible dopamine receptor antagonism.

    Conclusions:

    • Haloperidol and pimozide act directly on striatal cholinergic neurons via potent dopamine receptor blockade.
    • Reserpine likely acts indirectly by depleting biogenic amines.
    • Reversible dopamine receptor antagonists may have a less pronounced impact on striatal acetylcholine levels.