The effects of chronic
carbamazepine (CBZ) on the development and expression of
cocaine-kindled
seizures and
seizures produced by an acute injection of
cocaine were evaluated in BALB/cByJ, C57Bl/6J and SJL/J mice. The repeated administration of a subconvulsant dose of
cocaine initially resulted in the development of an increased sensitivity to the
convulsant effects of
cocaine in the three strains. Chronic, dietary
carbamazepine attenuated this initial sensitization to
cocaine-induced
seizures. While the continued administration of
cocaine resulted in a relatively permanent sensitization to
cocaine-induced
seizures among SJL mice, tolerance to
cocaine-induced
seizures ultimately developed among C57 mice and to a lesser degree among BALB mice. Genetic factors were found to mediate the effects of chronic CBZ on the development of sensitization and/or tolerance to the
convulsant effects of
cocaine. Among BALB mice, chronic CBZ appears to have eliminated the development of tolerance to
cocaine-induced
seizures and allowed an underlying sensitization to be manifest. Among SJL mice, however, the sensitization observed following repeated
cocaine injections was reduced, but not eliminated. Genetic factors were also found to be associated with the effects of CBZ on
seizures induced by the acute administration of
cocaine. BALB and C57 mice, but not SJL mice, chronically treated with dietary CBZ were less susceptible to a consulvant dose of
cocaine than their corresponding dietary controls for at least 72 h after stopping CBZ administration. In addition, there were genotype-specific lethal effects associated with the concurrent administration of CBZ and
cocaine.