Triphenyl phosphite-induced impairment of spatial alternation learning

Triphenyl phosphite (TPP) is a weak acetylcholinesterase inhibitor and a type II organophosphorus compound-induced delayed neurotoxic agent. The current study examined the cognitive effects of a single 250 mg/kg ip dose of TPP administered to either 3-mo- or 1-yr-old male Sprague-Dawley rats. Starting 4 d after TPP administration, the rats began training on a T-maze spatial alternation task for food reinforcement. Over five sessions of acquisition training, the TPP-treated rats showed significantly lower alternation scores than controls. There was no difference in spatial alternation performance in the first session, when both groups were performing at near-chance levels. In sessions 2-5, the controls improved dramatically to an average of 85.3 +/- 3.2% correct, while the TPP-treated rats did not significantly change, with 69.7 +/- 3.1 percent correct. During sessions 2 and 3 there was a significant TPP treatment-related deficit. This TPP-induced choice accuracy deficit was persistent in that it was seen well after the acute exposure. With continued training the TPP-exposed rats were able to learn the task as well as controls. There were no significant TPP effects on response latency. These data show that acute TPP administration has persistent effects of impairing T-maze learning that do not appear to result from effects on motor function.