DIHYDROPYRIDINE-SENSITIVE CALCIUM CHANNELS AND BARBITURATE TOLERANCE AND WITHDRAWAL

We have shown previously that the dihydropyridine calcium channel anta gonist nitrendipine, given chronically, prevents the development of et hanol tolerance and physical dependence. The present study examines th e effects on barbiturate tolerance and physical dependence. Nitrendipi ne, given acutely during withdrawal, provided little protection agains t barbiturate withdrawal, as measured by convulsive behaviour on handl ing. When nitrendipine was given chronically concurrently with the bar biturate, a prolonged protection against the withdrawal syndrome was s een. Acute nitrendipine significantly increased the latency of seizure s in response to the partial benzodiazepine inverse agonist FG7142 dur ing barbiturate withdrawal, but there was no effect on the seizure inc idence in response to bicuculline. Chronic treatment with nitrendipine did not alter the development of tolerance to the ataxic or general a naesthetic actions of barbiturates, but evidence was found of a possib le interaction between nitrendipine and pentobarbitone, which may have been pharmacokinetic. The results suggest that neuronal calcium chann els may be involved to some degree in the development of the changes r esponsible for barbiturate withdrawal. but to a less extent than found previously for ethanol dependence.