Effect of acute and chronic cholinesterase inhibition with diisopropylfluorophosphate on muscarinic, dopamine, and GABA receptors of the rat striatum

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

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91 Citations (Scopus)

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; 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.

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

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Isoflurophate
GABA Receptors
Cholinesterases
Dopamine Receptors
Muscarinic Receptors
Rats
Cholinergic Agents
Acetylcholinesterase
Corpus Striatum
Dopamine
Aminobutyrates
Diencephalon
Injections
Therapeutics
Brain

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Effect of acute and chronic cholinesterase inhibition with diisopropylfluorophosphate on muscarinic, dopamine, and GABA receptors of the rat striatum. / Sivam, Subbiah; Norris, J. C.; Lim, D. K.; Hoskins, B.; Ho, I. K.

In: Journal of Neurochemistry, Vol. 40, No. 5, 1983, p. 1414-1422.

Research output: Contribution to journalArticle

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