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

Individuals chronically exposed to low levels of organophosphate insecticid es 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 imp airment in performance of a spatial memory task and the protracted decrease in the expression of cholinergic receptors and acetylcholinesterase in spe cific brain regions. Cholinergic receptors labeled with the ligands [H-3]ep ibatidine and [H-3]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 [H-3]QNB. Pre-testing administration of nicotine was shown to completely reverse this DFP-induced impairment in mem ory-related task performance. Additionally, prophylaxis with pyridostigmine bromide (PB) caused DFP-treated animals to exhibit near normal levels of m emory-related task performance, These results are consistent with the devel opment of a protracted phase of learning impairment to sub-acute DFP exposu re, 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. All rights reserved.