ACTIONS OF RITANSERIN, A 5-HT2 1C ANTAGONIST, IN BENZODIAZEPINE-DEPENDENT RATS/

The effects of ritanserin on spontaneous benzodiazepine (BZ) withdrawa l-induced weight loss, anorexia and hypodipsia were studied. Groups of female rats initially received i.p. injections b.i.d. (11.00 and 17.0 0 h) of either saline or chlordiazepoxide (CDP). CDP doses increased b y 2 mg/kg/day from 10 mg/kg to a final dose of 30 mg/kg. Treatment was maintained for 26 days. Over the next 6 days animals were either trea ted b.i.d. with vehicle, CDP, or ritanserin at one of three doses (0.1 6,0.63 and 2.5 mg/kg). In CDP-pretreated animals subsequently treated with vehicle, significant weight loss, anorexia and hypodipsia were se en, relative to controls. In saline-pretreated animals ritanserin had no effect on body weight. However, CDP withdrawal-induced weight loss was actually exacerbated by ritanserin, in a dose-related fashion. Thu s, ritanserin potentiated withdrawal-induced weight loss, by a process which did not involve functional (additive) effects of withdrawal and ritanserin treatment. Ritanserin stimulated food intake in saline-pre treated animals. Despite this effect it failed to alleviate CDP withdr awal-induced anorexia. However, in contrast to the weight loss index, no evidence was obtained for potentiation of withdrawal-induced anorex ia. In saline-pretreated animals ritanserin had no effect on water int ake, nor did it alleviate or potentiate CDP withdrawal-induced hypodip sia. Thus the effects of ritanserin on somatic BZ withdrawal signs dep ended upon the specific sign studied, different signs showing potentia tion or no effect. However, for none of the signs studied was there an y evidence that ritanserin alleviated the effect of CDP withdrawal. 5- HT2/1C antagonists may therefore be of limited value in the treatment of somatic aspects of the BZ withdrawal syndrome. They may even exacer bate some BZ withdrawal signs, although a full characterization of the effects of such drugs on BZ withdrawal requires that a number of othe r different withdrawal signs and symptoms should be studied, since it seems likely that different BZ withdrawal signs involve different unde rlying mechanisms.