Reversal of phenytoin-induced impairment of spontaneous alternation by piracetam in mice: Involvement of cholinergic system

Objective: To study the effect of the combined treatment of phenytoin and piracetam on seizure control, cognitive and motor functions in mice.
Material and Methods: Increasing current electroshock seizure (ICES) test was used to evaluate the effect of the combination of phenytoin and piracetam on convulsions. Cognitive functions in mice were assessed by spontaneous alternation in behavior on a plus maze while motor functions were screened using rolling roller apparatus and by counting the number of arms entries on a plus maze. Brain acetylcholinesterase (AChE) activity was measured using the Ellman et al method.
Results: The study showed that piracetam when co-administered with phenytoin, significantly reversed phenytoin-induced reduction in spontaneous alternation without altering the efficacy of phenytoin against ICES in both acute and chronic studies. Further, it also reversed phenytoin-induced increase in AChE activity.
Conclusion: Piracetam alleviated the phenytoininduced cognitive impairment without compromising its antiepileptic efficacy.

Keywords
Acetylcholinesterase, cognitive functions, diphenylhydantoin, piracetam.