RO-15-4513 ALTERATION OF PENTOBARBITAL DEPENDENCE

This study investigated the ability of the benzodiazepine inverse agon ist, Ro 15-4513, to alter the expression of physical dependence on pen tobarbital. Male Sprague-Dawley rats were made physically dependent on pentobarbital by continuous, IP, infusion of escalating doses of pent obarbital for 12 days. In Experiment 1, pentobarbital dependent rats r eceived either vehicle or Ro 15-4513, in doses of 5, 10, or 15 mg/kg, IF, periodically during the pentobarbital abstinence period. As expect ed, Ro 15-4513 produced a significant. dose-dependent, exacerbation of withdrawal signs in the pentobarbital dependent rats. In Experiment 2 , either vehicle or Ro 15-4513, at a dose of 15 mg/kg, was administere d, IF, once daily during the 12 days of continuous pentobarbital infus ion. During the subsequent pentobarbital abstinence period it was note d that the withdrawal signs were significantly reduced in the rats rec eiving the daily administration of Ro 15-4513. It is hypothesized that the benzodiazepine inverse agonist, Ro 15-4513, may inhibit the devel opment of physical dependence on pentobarbital through an opposing act ion on the GABA-A receptor. Copyright (C) 1996 Elsevier Science Inc.