EXPRESSION OF C-FOS MESSENGER-RNA IN ACUTE AND KINDLED COCAINE SEIZURES IN RATS

In situ hybridization for c-fos mRNA was performed on brain sections (a) from rats after an acute cocaine-induced seizure or from saline-injected controls and (b) from rats after their first cocaine-kindled seizure, as well as from rats that had not yet developed cocaine-kindled seizures (but were exposed to the same amount of cocaine as those that did exhibit convulsions) and from saline-injected controls. Increased expression of c-fos mRNA was observed in animals demonstrating cocaine-induced seizures acutely or following pharmacological kindling. Rats that experienced acute seizures after cocaine (65 mg/kg) showed pronounced increase in expression of c-fos mRNA in the dentate gyrus of the hippocampus and olfactory bulb. Increases were also observed in several other limbic cortical regions, as well as the striatum and ventromedial hypothalamic nucleus (VMH). In rats that were injected daily with an initially subconvulsive dose of cocaine-HCI (40 mg/kg), the cocaine-kindled seizures induced elevations in c-fos mRNA in the same brain regions as with an acute cocaine-induced seizure with the single exception of the VMH. These findings not only suggest the involvement of limbic, cortical and striatal structures in the cocaine-induced seizure, but also raise the possibility that alterations in the proto-oncogene c-fos and its subsequent impact on gene expression could play a rol in the changes in neural excitability associated with cocaine-induced kindling.