Comparative effects of continuous infusion of mCPP, Ro 60-0175 and d-fenfluramine on food intake, water intake, body weight and locomotor activity inrats

1 The aim of the study was to compare the effects of 14 day subcutaneous in fusion of the 5-HT2C receptor agonists, m-chlorophenylpiperazine (mCPP, 12m g kg(-1) day(-1)) and Ro 60-0175 (36 mg kg(-1) day(-1)) and the 5-HT releas ing agent and re-uptake inhibitor, d-fenfluramine (6 mg kg(-1) day(-1)), on food and water intake, body weight gain and locomotion in lean male Lister hooded rats. 2 Chronic infusion of all three drugs significantly reduced food intake and attenuated body weight gain. In contrast, drug infusion did not lead to si gnificant reductions in locomotor activity in animals assessed 2 and 13 day s after pump implantation. 3 In a subsequent 14 day study that was designed to identify possible toler ance during days 7-14, animals were given a subcutaneous infusion of mCPP ( 12 mg kg(-1) day(-1)) or d-fenfluramine (6 mg kg(-1) day(-1)) for either 7 or 14 days. During the first 7 days both drugs significantly reduced body w eight gain compared to saline-infused controls; however, from day 7 onwards animals withdrawn from drug treatment exhibited an increase in body weight such that by day 14 they were significantly heavier than their 14-day drug -treated counterparts. 4 Both mCPP and d-fenfluramine reduced daily food intake throughout the inf usion periods. For lit-day treated animals this hypophagia was marked durin g the initial week of the study but only minor during the second week. In l ight of the sustained drug effect on body weight, the data suggest that wei ght loss by 5-HT2C receptor stimulation may be only partly dependent on cha nges in food consumption and that 5-HT2C receptor agonists may have effects on thermogenesis. 5 These data suggest tolerance does not develop to the effects of d-fenflur amine, mCPP and Ro 60-0175 on rat body weight gain.