Periodic orbit analysis reveals subtle effects of atropine on epileptiform activity in the guinea-pig hippocampal slice.

Abstract

Epileptiform activity is a state often induced in vitro in order to study seizures and antiepileptic/anticonvulsant drugs. Traditional methods of evaluating drug effects have commonly relied upon measuring changes in the frequency and duration of such events. We have used a recently developed mathematical technique based on periodic orbit analysis to investigate the effect of atropine (a muscarinic antagonist) on epileptiform activity induced by soman (an irreversible acetylcholinesterase inhibitor), 4-aminopyridine (a K+ channel blocker) and 8-cyclopentyl-1,3-dipropylxanthine (an adenosine A1 receptor antagonist) in the guinea-pig hippocampal slice. This technique showed that significant changes in periodic orbits can occur without an accompanying change in burst rate. These results suggest that periodic orbit analysis may be useful in detecting and predicting novel actions of anticonvulsant drugs.