CHRONIC COCAINE INTOXICATION ALTERS HIPPOCAMPAL SODIUM-CHANNEL FUNCTION

Repeated daily administration of subconvulsive doses of cocaine result s in the appearance and increase in convulsive responsiveness to the d rug and its lethal effects. The mechanisms involved in this increased susceptibility to cocaine-induced seizure are yet unknown. In this stu dy, we used whole cell patch-clamp recording techniques to examine the functional changes in voltage-dependent Na+ channels produced by subc onvulsive 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 i n vitro. Our results show that an augmentation of peak Na+ currents an d a shift in depolarizing direction of the steady-state inactivation w ere present in neurons from drug-treated rats. These changes, by makin g a larger proportion of Na+ channels available for opening, could inc rease the excitability of CA1 neurons and may contribute to the increa se in convulsive responsiveness to cocaine. (C) 1997 Elsevier Science Ireland Ltd.