Ro 15-4513 alteration of pentobarbital dependence.
This study investigated the ability of the benzodiazepine inverse agonist, Ro 15-4513, to alter the expression of physical dependence on pentobarbital. Male Sprague-Dawley rats were made physically dependent on pentobarbital by continuous. IP, infusion of escalating doses of pentobarbital for 12 days. In Experiment 1, pentobarbital dependent rats received either vehicle or Ro 15-4513, in doses of 5, 10, or 15 mg/kg, IP, periodically during the pentobarbital abstinence period. As expected, 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 administered, IP, once daily during the 12 days of continuous pentobarbital infusion. During the subsequent pentobarbital abstinence period it was noted that the withdrawal signs were significantly reduced in the rats receiving the daily administration of Ro 15-4513. It is hypothesized that the benzodiazepine inverse agonist, Ro 15-4513, may inhibit the development of physical dependence on pentobarbital through an opposing action on the GABA-A receptor.
Yutrzenka
G J
GJ
Department of Physiology and Pharmacology, School of Medicine, University of South Dakota, Vermillion 57069, USA.
Stone
T
T
Anderson
S
S
D000818:Animals; D001386:Azides / Q000008:administration & dosage / Q000494:pharmacology*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000819:agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D010424:Pentobarbital; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D019966:Substance-Related Disorders; D013997:Time Factors; D015431:Weight Loss
D001386:Azides; D011963:Receptors, GABA-A; D001569:Benzodiazepines; C042957:Ro 15-4513; D010424:Pentobarbital