title: Protractive effects of chronic treatment with an acutely sub-toxic regimen of diisopropylflurophosphate on the expression of cholinergic receptor densities in rats.
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 [(3)H]epibatidine and [(3)H]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 [(3)H]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.
authors.affiliation: Alzheimer's Research Center, Department of Pharmacology and Toxicology, Medical College of Georgia, and the Veterans Affairs Medical Center, Augusta, GA 30912-2300, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Stone
authors.forename: A V
authors.initials: AV
authors.lastname: Terry
authors.forename: J R
authors.initials: JR
authors.lastname: Pauly
authors.forename: M A
authors.initials: MA
authors.lastname: Prendergast
authors.forename: J J
authors.initials: JJ
authors.lastname: Buccafusco
mesh_terms: D000110:Acetylcholinesterase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D007531:Isoflurophate / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000187:drug effects* / Q000378:metabolism
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D002800:Cholinesterase Inhibitors; D011725:Pyridines; D011950:Receptors, Cholinergic; C065959:AFDX 384; D007531:Isoflurophate; D010890:Pirenzepine; D000110:Acetylcholinesterase; D011729:Pyridostigmine Bromide; C082748:epibatidine