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 impai rs acetylcholine (ACh) degradation by acetylcholinesterase (AChE) and, in humans, may produce lasting neurotoxicity affecting cognitive func tion, The present studies examined the ability of such exposure to imp air performance of well-learned cognitive tasks in two species, nonhum an 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-t o-sample task (DMTS), However, erythrocyte AChE activity was reduced f rom 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 dos e for 15 days, DMTS performance remained at or above baseline levels, DMTS accuracy was moderately, but not significantly, reduced after tit ration to a dose of 0.02 mg/kg. However, decrements were associated wi th mild, overt symptoms of OP toxicity and performance returned to bas eline levels after withdrawal from OP exposure. In rats, chronic expos ure 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 memo ry tasks dependent upon reference concepts is not impaired by OP expos ure regimens that impair acquisition of novel cognitive tasks prior to the onset of overt toxicity. (C) 1998 Elsevier Science Inc.