Physical dependence on diazepam: precipitation of abstinence syndromes by peripheral and central benzodiazepine receptor antagonists.

This work was performed to compare withdrawal symptoms induced by the administration of the central vs. peripheral benzodiazepine antagonists in rats treated chronically with diazepam (15 mg/kg, SC) for 8 days. Withdrawal was expressed as motor, autonomic, and behavioral signs. Significant withdrawal occurred after the administration of both flumazenil (15 and 20 mg/kg, IP) and PK11195 (5 and 10 mg/kg, IP). With these doses, PK11195 induced diarrhea and decreased motor activity more than did flumazenil. These preliminary results suggest that peripheral benzodiazepine receptors are involved in the withdrawal syndrome in diazepam-dependent rats.