Protractive effects of chronic treatment with an acutely sub-toxic regimen of diisopropylflurophosphate on the expression of cholinergic receptor densities in rats

J. Derek Stone, Alvin V. Terry, James R. Pauly, Mark A. Prendergast, Jerry J. Buccafusco

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Individuals chronically exposed to low levels of organophosphate insecticides may present with subtle impairments in cognition. In addition, low level diisopropylflurophosphate (DFP) exposure (0.25 mg/kg per day for 2 weeks) in rats resulted in protracted working memory impairment [29]. The current studies attempt to show a temporal relationship between the DFP-induced impairment in performance of a spatial memory task and the protracted decrease in the expression of cholinergic receptors and acetylcholinesterase in specific brain regions. Cholinergic receptors labeled with the ligands [3H]epibatidine and [3H]AFDX-384 were affected to a much greater extent and for a longer period of time than were both acetylcholinesterase activities and cholinergic receptors labeled with [3H]QNB. Pre-testing administration of nicotine was shown to completely reverse this DFP-induced impairment in memory-related task performance. Additionally, prophylaxis with pyridostigmine bromide (PB) caused DFP-treated animals to exhibit near normal levels of memory-related task performance. These results are consistent with the development of a protracted phase of learning impairment to sub-acute DFP exposure, which may involve the loss of hippocampal nicotinic receptors, and may be prevented or reversed by PB or nicotine, respectively. (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)9-18
Number of pages10
JournalBrain Research
Volume882
Issue number1-2
DOIs
StatePublished - Nov 3 2000

Bibliographical note

Funding Information:
This work was partly supported by DAMD17-95-1-5036. The content of the information of this study does not necessarily reflect the position or the policy of the government, and no official endorsement should be inferred. This work also was partly supported by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs.

Keywords

  • Acetylcholinesterase
  • Cholinergic receptor
  • DFP
  • Memory
  • Organophosphate
  • Pyridostigmine bromide
  • Spatial learning

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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