Yutrzenka G J, Stone T, Anderson S
Department of Physiology and Pharmacology, School of Medicine, University of South Dakota, Vermillion 57069, USA.
Pharmacol Biochem Behav. 1996 Nov;55(3):379-86. doi: 10.1016/s0091-3057(96)00107-4.
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.
本研究调查了苯二氮䓬类反向激动剂Ro 15-4513改变对戊巴比妥身体依赖性表达的能力。通过连续腹腔注射递增剂量的戊巴比妥12天，使雄性Sprague-Dawley大鼠对戊巴比妥产生身体依赖性。在实验1中，戊巴比妥依赖大鼠在戊巴比妥戒断期定期腹腔注射溶剂或5、10或15 mg/kg剂量的Ro 15-4513。正如预期的那样，Ro 15-4513在戊巴比妥依赖大鼠中产生了显著的、剂量依赖性的戒断症状加重。在实验2中，在连续腹腔注射戊巴比妥的12天期间，每天一次腹腔注射溶剂或15 mg/kg剂量的Ro 15-4513。在随后的戊巴比妥戒断期，注意到每日接受Ro 15-4513注射的大鼠戒断症状明显减轻。据推测，苯二氮䓬类反向激动剂Ro 15-4513可能通过对GABA-A受体的拮抗作用抑制对戊巴比妥身体依赖性的发展。
