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Related Experiment Videos

Chronic scopolamine treatment and brain cholinergic function.

M J Marks, M F O'Connor, L D Artman

    Pharmacology, Biochemistry, and Behavior
    |May 1, 1984
    PubMed
    Summary
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    Chronic scopolamine administration in mice increased brain muscarinic receptors, leading to heightened sensitivity to agonists. However, this receptor increase was not consistently dose-dependent, suggesting a complex relationship between receptor levels and physiological response.

    Area of Science:

    • Neuropharmacology
    • Receptor Pharmacology
    • Cholinergic System

    Background:

    • Scopolamine is an anticholinergic drug that affects the central nervous system.
    • Muscarinic receptors play a crucial role in neurotransmission and physiological responses.
    • Understanding drug-induced receptor plasticity is vital for therapeutic development.

    Purpose of the Study:

    • To investigate the effects of chronic scopolamine administration on brain muscarinic receptors.
    • To examine the relationship between muscarinic receptor changes and agonist-induced responses.
    • To explore dose-dependency and potential dissociation between receptor number and functional supersensitivity.

    Main Methods:

    • Continuous infusion and daily injection of scopolamine in C3H mice.

    Related Experiment Videos

  • Measurement of brain acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities.
  • Quantification of muscarinic receptors using quinuclidinyl benzilate (QNB) binding assays.
  • Assessment of supersensitivity to the muscarinic agonist oxotremorine (hypothermia and tremor).

    • Main Results:

    • Chronic scopolamine infusion induced supersensitivity to oxotremorine and increased brain muscarinic receptor density (QNB binding).
    • The increase in QNB binding showed a complex dose-response relationship, with maximal effects at lower doses and normalization at higher doses in most brain regions.
    • Despite changes in receptor binding, a dissociation between receptor number and agonist response was observed, as animals remained supersensitive even when QNB binding returned to control levels.
    • Chronic oxotremorine infusion led to tolerance and decreased QNB binding, effects blocked by co-infusion with scopolamine.

    Conclusions:

    • Chronic scopolamine treatment can upregulate brain muscarinic receptors and induce functional supersensitivity to agonists.
    • The observed effects are not strictly dose-dependent, and a direct correlation between receptor number and agonist response may not always exist.
    • These findings highlight the complex adaptive mechanisms within the cholinergic system in response to chronic drug exposure.