Chronic cocaine intoxication alters hippocampal sodium channel function

Repeated daily administration of subconvulsive doses of cocaine results in the appearance and increase in convulsive responsiveness to the drug and its lethal effects. The mechanisms involved in this increased susceptibility to cocaine-induced seizure are yet unknown. In this study, we used whole cell patch-clamp recording techniques to examine the functional changes in voltage-dependent Na+ channels produced by subconvulsive doses of cocaine (45 mg/kg per day, i.p.) in rat hippocampal CA1 pyramidal neurons. Intact animals were injected with cocaine for 5-6 days. Acutely dissociated hippocampal neurons were then recorded in vitro. Our results show that an augmentation of peak Na+ currents and a shift in depolarizing direction of the steady-state inactivation were present in neurons from drug-treated rats. These changes, by making a larger proportion of Na+ channels available for opening, could increase the excitability of CA1 neurons and may contribute to the increase in convulsive responsiveness to cocaine.