Effects of chronic, low-level organophosphate exposure on delayed recall, discrimination, and spatial learning in monkeys and rats.
Chronic exposure to low levels of organophosphate (OP) compounds impairs acetylcholine (ACh) degradation by acetylcholinesterase (AChE) and, in humans, may produce lasting neurotoxicity affecting cognitive function. The present studies examined the ability of such exposure to impair performance of well-learned cognitive tasks in two species, nonhuman primates and rats. During 25 days of exposure to a 0.01 mg/kg dose of the OP diisopropylfluorophosphate (DFP), mature adult monkeys were not impaired in their performance of a well-learned delayed matching-to-sample task (DMTS). However, erythrocyte AChE activity was reduced from predrug levels by 76.26 +/- 3.33% by 14 days after the initiation of DFP administration. Following titration of DFP to a 0.015 mg/kg dose for 15 days, DMTS performance remained at or above baseline levels. DMTS accuracy was moderately, but not significantly, reduced after titration to a dose of 0.02 mg/kg. However, decrements were associated with mild, overt symptoms of OP toxicity and performance returned to baseline levels after withdrawal from OP exposure. In rats, chronic exposure to a low-dose regimen of DFP (0.25 mg/kg/day for 14 days) impaired the ability to initially learn a spatial navigation task, but did not impair performance of previously learned stimulus discrimination and spatial navigation tasks. These data indicate that performance of memory tasks dependent upon reference concepts is not impaired by OP exposure regimens that impair acquisition of novel cognitive tasks prior to the onset of overt toxicity.
Prendergast
M A
MA
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912, USA.
Terry
A V
AV
Buccafusco
J J
JJ
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004192:Discrimination, Psychological / Q000187:drug effects*; D005260:Female; D007531:Isoflurophate / Q000633:toxicity*; D007858:Learning / Q000187:drug effects*; D008253:Macaca mulatta; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D002800:Cholinesterase Inhibitors; D007531:Isoflurophate