Effect of Acute and Chronic Cholinesterase Inhibition with Diisopropylfluorophosphate on Muscarinic, Dopamine, and GABA Receptors of the Rat Striatum

S. P. Sivam, J. C. Norris, D. K. Lim, B. Hoskins, I. K. Ho

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

Abstract: The effects of acute and chronic administration of diisopropylfluorophosphate (DFP) to rats on acetylcholinesterase (AChE) activity (in striatum, medulla, diencephalon, cortex, and medulla) and muscarinic, dopamine (DA), and γ‐aminobutyric acid (GABA) receptor characteristics (in striatum) were investigated. After a single injection of (acute exposure to) DFP, striatal region was found to have the highest degree of AChE inhibition. After daily DFP injections (chronic treatment), all brain regions had the same degree of AChE inhibition, which remained at a steady level despite the regression of the DFP‐induced cholinergic overactivity. Acute administration of DFP increased the number of DA and GABA receptors without affecting the muscarinic receptor characteristics. Whereas chronic administration of DFP for either 4 or 14 days reduced the number of muscarinic sites without affecting their affinity, the DFP treatment caused increase in the number of DA and GABA receptors only after 14 days of treatment; however, the increase was considerably lower than that observed after the acute treatment. The in vitro addition of DFP to striatal membranes did not affect DA, GABA, or muscarinic receptors. The results indicate an involvement of GABAergic and dopaminergic systems in the actions of DFP. It is suggested that the GABAergic and dopaminergic involvement may be a part of a compensatory inhibitory process to counteract the excessive cholinergic activity produced by DFP. 1983 International Society for Neurochemistry

Original languageEnglish (US)
Pages (from-to)1414-1422
Number of pages9
JournalJournal of Neurochemistry
Volume40
Issue number5
DOIs
StatePublished - May 1983
Externally publishedYes

Keywords

  • Acetylcholinesterase
  • Diisopropylfluorophosphate
  • Dopamine receptors
  • GABA receptors
  • Tolerance

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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