Modulation of central cholinergic activity by GABA and serotonin

PET studies with11C-benztropine in primates

Stephen L. Dewey, Gwenn Smith, Jean Logan, Jonathan D. Brodie

Research output: Contribution to journalArticle

Abstract

The pharmacologic treatment of many neuropsychiatric disorders (Alzheimer's disease, schizophrenia, depressive illness) has been targeted at the central hypothesis that defects in a single neurotransmitter system underlie the pathophysiology of the disease state. With the recognition that such treatments have not been efficacious consistently, recent drug development has been directed at altering other functionally linked neurotransmitters involved in these diseases. Using positron emission tomography, we have noninvasively investigated the effects of two noncholinergic drugs on the release of acetylcholine. By examining the effects of gamma-vinyl gamma-aminobutyric acid (GABA) (a GABA transaminase inhibitor) or altanserin (a serotonergic antagonist) on the regional binding of 11C-benztropine in the primate brain (Papio anubis), we demonstrated that drugs acting upon either GABAergic or serotonergic neurons produce profound regional changes in acetylcholine release. These findings indicate that the mechanisms of action and the subsequent therapeutic efficacy of these centrally acting drugs may be linked to their multitransmitter effects. This application of positron emission tomography represents an extremely promising experimental approach that can be directed towards elucidating abnormalities in neurotransmitter modulation relevant to disease progression and pharmacologic treatment.

Original languageEnglish (US)
Pages (from-to)371-376
Number of pages6
JournalNeuropsychopharmacology
Volume8
Issue number4
StatePublished - 1993
Externally publishedYes

Fingerprint

Benztropine
gamma-Aminobutyric Acid
Cholinergic Agents
Primates
Neurotransmitter Agents
Serotonin
Positron-Emission Tomography
Acetylcholine
Papio anubis
Pharmaceutical Preparations
Vigabatrin
Serotonergic Neurons
GABAergic Neurons
Transaminases
Disease Progression
Schizophrenia
Alzheimer Disease
Brain
Therapeutics

Keywords

  • Altanserin
  • Benztropine
  • GABA
  • Gamma-vinyl GABA
  • Interactions
  • Positron emission tomography
  • Serotonin

ASJC Scopus subject areas

  • Pharmacology

Cite this

Modulation of central cholinergic activity by GABA and serotonin : PET studies with11C-benztropine in primates. / Dewey, Stephen L.; Smith, Gwenn; Logan, Jean; Brodie, Jonathan D.

In: Neuropsychopharmacology, Vol. 8, No. 4, 1993, p. 371-376.

Research output: Contribution to journalArticle

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