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Cholecystokinin receptor subtypes and neuromodulation.

C A Altar1

  • 1Pharmacological Sciences, Genentech, Inc., South San Francisco, California 94080.

Progress in Neuro-Psychopharmacology & Biological Psychiatry
|January 1, 1989
PubMed
Summary

Cholecystokinin (CCK) receptor subtypes in the brain were investigated for their role in dopamine release. CCK-B receptors were found to suppress dopamine release, suggesting potential therapeutic applications for psychiatric disorders.

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Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Cholecystokinin (CCK) is a peptide neurotransmitter with diverse roles in the central nervous system.
  • CCK receptors are implicated in regulating neurotransmitter release, including dopamine (DA).

Purpose of the Study:

  • To determine the specific CCK receptor subtype and location responsible for modulating dopamine release in the brain.
  • To investigate the effects of CCK-8S and CCK fragments on basal and amphetamine-induced dopamine release.

Main Methods:

  • Administration of sulfated octapeptide of cholecystokinin (CCK-8S) and CCK fragments (CCK-8U, t-boc-CCK-4) to mice via central (i.c.v.) and peripheral (s.c.) routes.
  • Assessment of dopamine release and metabolism in brain regions like the neostriatum and olfactory tubercle.
  • Utilized CCK-A receptor antagonist (L 364,718) to differentiate receptor actions.

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Main Results:

  • Central and peripheral CCK-8S administration reduced dopamine release and metabolism in the neostriatum and olfactory tubercle.
  • CCK-B selective compounds (CCK-8U, t-boc-CCK-4) decreased dopamine release when administered centrally but not peripherally.
  • CCK-8S and CCK-B selective compounds attenuated amphetamine-induced dopamine release when given centrally.
  • CCK-A receptor antagonist did not block the peripheral effects of CCK-8S.

Conclusions:

  • CCK-B receptors in the brain mediate the suppression of both basal and augmented dopamine release by CCK.
  • CCK-B receptor agonists show potential for treating psychiatric conditions associated with excessive dopamine release.