Protractive effects of chronic treatment with an acutely sub-toxic regimen of diisopropylflurophosphate on the expression of cholinergic receptor densities in rats.
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.
Stone
J D
JD
Alzheimer's Research Center, Department of Pharmacology and Toxicology, Medical College of Georgia, and the Veterans Affairs Medical Center, Augusta, GA 30912-2300, USA.
Terry
A V
AV
Pauly
J R
JR
Prendergast
M A
MA
Buccafusco
J J
JJ
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
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