PHENYTOIN BLOCKS THE REVERSAL OF A CLASSICALLY-CONDITIONED DISCRIMINATIVE EYEBLINK RESPONSE IN RABBITS

Purpose: Cognitive deficits associated with chronic treatment with phe nytoin (PHT) have been reported. PHT blocks transfer from a signaled a ppetitive bar press to an active avoidance response in rats. We invest igated the effects of PHT and the prodrug fosphenytoin in rabbits requ ired to learn a discrimination and reversal of a classical eyeblink co nditioning paradigm. Methods: Before drug treatment was started, rabbi ts were trained to produce a discriminated eyeblink response. PHT (n = 7) was administered centrally or the prodrug fosphenytoin (n = 2) was given systemically. Control animals were similarly treated centrally with either saline (n = 3) pr no drug treatment (n = 13). Rabbits were then challenged with a stimulus reversal while being maintained on th e respective drug. Results: On the first day of reversal training, con trol animals typically displayed high response rates to both tones, fo llowed by a reduction in responsiveness to the new conditioned stimulu s (CS-) in the ensuing days. In contrast, PMT-treated animals failed t o suppress responsiveness to the new CS-. Conclusions: The response pa tterns observed are similar to those observed in rabbits with hippocam pal ablations, leading us to suggest that the adverse effects of pheny toin may be due to actions in the hippocampus.