ASSESSMENT OF THE BENZODIAZEPINE-LIKE DEPENDENCE POTENTIAL IN RATS OFTHE PUTATIVE 5-HT1A AGONIST ANXIOLYTIC S-20499

The dependence potential of the putative 5-HT1A agonist anxiolytic S-2 0499 was assessed in rats in a study in which the benzodiazepine chlor diazepoxide (CDP) was used as a ''positive control''. S-20499 was admi nistered b.i.d. (at 10.00 and 16.00 h) for 21 days, at constant doses of either 0.5, 3 or 18 mg/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 effe cts. When S-20499 was withdrawn there was no evidence of any effect on body weight or food intake.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 10.0 0 and 16.00 h) for 21 days at doses escalated from 10 to 30 mg/kg i.p. CDP differed from S-20499 in some of its acute effects, stimulating b ody weight and food intake. In contrast to S-20499 withdrawal, CDP wit hdrawal induced weight loss and aphagia. Acutely, S-20499 resembled CD P 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 potentia l after administration for a relatively long period of time, at doses that are substantially greater than ''anxiolytic doses'' in rats.