EFFECTS OF ANTICONVULSANTS IN A NOVEL OPERANT LEARNING-PARADIGM IN RATS - COMPARISON OF REMACEMIDE HYDROCHLORIDE AND FPL 15896AR TO OTHER ANTICONVULSANT AGENTS

One of the primary undesired effects of anticonvulsant medication is a n impairment in cognitive function, such as new learning ability. The purpose of the present study was to compare the effects of remacemide hydrochloride -)-2-amino-N(1-methyl-1,2,-diphenylethyl)acetamide monoh ydrochloride] and FPL 15896AR [(+)-alpha-phenyl-2-pyridine-ethanamide] to a number of anticonvulsant agents on an operant acquisition baseli ne. Remacemide hydrochloride is currently in clinical trials for epile psy and FPL 15896AR is under development. In the present procedure, fa sted, experimentally naive rats were placed into operant chambers in w hich food pellets were initially available under a Fixed-Ratio 1 (FR1) schedule of food presentation, and as lever pressing progressed, the FR value incremented. All drugs were tested in multiples of three and ten times their respective ED(50) values against maximal electroshock- induced seizure (MES) following p.o. administration. The drugs tested varied widely in their ability to disrupt acquisition of the lever-pre ssing task. Remacemide hydrochloride and a structurally related analog , FPL 15896AR, did not disrupt acquisition. Clonazepam, lamotrigine, M K-801, phenobarbital, felbamate, phenytoin, and carbamazepine increase d the number of hours required to achieve FR3 (emit more than 100 resp onses) with respect to vehicle control performance. Of these, clonazep am, MK-801 and phenytoin produced robust enough disruption to result i n significantly fewer reinforcers delivered over the 14-h operant sess ion.