Repeated exposure to diisopropylfluorophosphate (DFP) produces increased sensitivity to cholinergic antagonists in discrimination retention and reversal.

This experiment examined the effects of repeated exposure to diisopropylfluorophosphate (DFP), an organophosphate anticholinesterase, on the retention and reversal of a visual discrimination and on the number of muscarinic receptors in the brain. Rats were trained in a serial reversal procedure. After achieving stable performance, the rats were divided into two groups. One group received repeated injections of DFP, the other group received injections. To determine whether DFP-treated rats would be more sensitive than normal rats to stresses on the cholinergic system, each rat was injected with saline or one of three doses of scopolamine, a muscarinic receptor blocker, prior to testing on every 6th day. DFP alone caused no impairment in performance. Scopolamine produced a greater impairment in DFP-treated rats than in control rats. Similar results were obtained in a second behavioral task, match-to-sample in a water maze, using the same DFP treatment protocol and only one dose of scopolamine. The number of muscarinic receptors and acetylcholinesterase activity levels were reduced on the 2nd and 15th day after the end of DFP treatment. These results demonstrate that although repeated exposure to organophosphate anticholinesterases may not alter discrimination behavior directly, it may compromise the central nervous system so that it cannot react normally when challenged.