Goudie A.J., Leathley M.J., Cowgill J.
Department of Psychology, University of Liverpool, PO Box 147, Liverpool L69 3BX, UK.
Behav Pharmacol. 1994 Apr;5(2):131-140. doi: 10.1097/00008877-199404000-00004.
The dependence potential of the putative 5-HT(1A) agonist anxiolytic S-20499 was assessed in rats in a study in which the benzodiazepine chlordiazepoxide (CDP) was used as a "positive control". S-20499 was administered b.i.d. (at 10.00 and 16.00h) for 21 days, at constant doses of either 0.5, 3 or 18mg/kg i.p. Subsequently, spontaneous withdrawal from S-20499 was studied over 7 days. Acutely, S-20499 decreased body weight and food intake and complete tolerance developed to these effects. When S-20499 was withdrawn there was no evidence of any effect on body weight or food intake. CDP was also administered b.i.d. (at 10.00 and 16.00h) for 21 days at doses escalated from 10 to 30mg/kg i.p. CDP differed from S-20499 in some of its acute effects, stimulating body weight and food intake. In contrast to S-20499 withdrawal, CDP withdrawal induced weight loss and aphagia. Acutely, S-20499 resembled CDP in inducing hypothermia. Full tolerance developed to this effect of both drugs. However, only CDP withdrawal induced hyperthermia. Thus S-20499 appeared to be devoid of benzodiazepine-like dependence potential after administration for a relatively long period of time, at doses that are substantially greater than "anxiolytic doses" in rats.
在一项以苯二氮䓬类药物氯氮卓（CDP）作为“阳性对照”的大鼠研究中，评估了假定的5-羟色胺（5-HT）（1A）激动剂抗焦虑药S-20499的潜在依赖性。S-20499每天两次（上午10点和下午4点）给药，持续21天，腹腔注射剂量分别为0.5、3或18mg/kg。随后，对S-20499进行了为期7天的自发撤药研究。急性给药时，S-20499可降低体重和食物摄入量，且对这些作用产生了完全耐受性。撤用S-20499后，未发现对体重或食物摄入量有任何影响。CDP也每天两次（上午10点和下午4点）给药，持续21天，腹腔注射剂量从10mg/kg逐步增至30mg/kg。CDP的一些急性作用与S-20499不同，它可刺激体重和食物摄入量。与撤用S-20499相反，撤用CDP会导致体重减轻和食欲不振。急性给药时，S-20499与CDP一样可引起体温过低。两种药物对此作用均产生了完全耐受性。然而，只有撤用CDP会引起体温过高。因此，在以远高于大鼠“抗焦虑剂量”的剂量给药相对较长时间后，S-20499似乎没有类似苯二氮䓬类药物的潜在依赖性。
