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Related Experiment Videos

A novel action of morphine in the rat locus coeruleus: persistent decrease in adenylate cyclase.

D B Beitner1, R S Duman, E J Nestler

  • 1Laboratory of Molecular Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06508.

Molecular Pharmacology
|May 1, 1989
PubMed
Summary
This summary is machine-generated.

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Acute in vivo morphine causes a persistent decrease in locus coeruleus (LC) adenylate cyclase activity. This novel effect, distinct from in vitro inhibition, may contribute to opiate addiction development.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Previous studies showed acute in vitro morphine inhibits adenylate cyclase, while chronic in vivo treatment increases it.
  • A novel action of morphine on adenylate cyclase in the rat locus coeruleus (LC) is investigated.

Purpose of the Study:

  • To characterize a novel, persistent decrease in adenylate cyclase activity in the LC following acute in vivo morphine administration.
  • To differentiate this effect from acute in vitro opiate inhibition and explore its mechanism and specificity.

Main Methods:

  • Acute in vivo morphine administration to rats.
  • Measurement of adenylate cyclase activity in isolated rat locus coeruleus (LC) membranes.
  • Inclusion of naloxone or naltrexone during in vivo or in vitro assays.
  • Comparison of effects in LC versus other brain regions (dorsal raphe, neostriatum, frontal cortex).

Related Experiment Videos

  • Administration of clonidine and other drugs for comparison.

    • Main Results:

    • Acute in vivo morphine caused a 25-30% persistent decrease in LC adenylate cyclase activity, observable in vitro.
    • This effect was dose-dependent, mediated by opiate receptors (prevented by naltrexone), and specific to the LC.
    • Acute in vivo clonidine produced a similar persistent decrease in LC adenylate cyclase activity.
    • The effect was distinct from acute in vitro opiate inhibition and not reversed by naloxone.

    Conclusions:

    • Acute in vivo morphine induces a persistent, opiate receptor-mediated decrease in LC adenylate cyclase activity.
    • This effect is specific to the LC and may represent an early step in the development of opiate addiction.
    • Similar effects with clonidine suggest a common pathway for drugs acting on the LC.