Changes in Seizure Susceptibility to Local Anesthetics by Repeated Administration of Cocaine and Nomifensine but Not GBR12935:Possible Involvement of Noradrenergic System

Abstract

We examined cross−sensitization of cocaine and synthetic local anesthetics to their seizure susceptibility after repeated administration.Seizure susceptibility of procaine and lidocaine increased after the end of two days of treatment with a subconvulsive dose of cocaine.Acute treatment with nomifensine but not GBR12935, a specific inhibitor of the dopamine transporter, facilitated lidocaine−induced convulsion.Furthermore, daily treatment with nomifensine for two days enhanced lidocaine−induced convulsion.These results suggest the possible involvement of the brain noradrenergic system in the changes in seizure susceptibility after repeated administration of some local anesthetics.