1. The aim of the study was to compare the effects of 14 day
subcutaneous infusion of the
5-HT(2C) receptor agonists,
m-chlorophenylpiperazine (mCPP, 12 mg kg(-1) day(-1)) and
Ro 60-0175 (36 mg kg(-1) day(-1)) and the
5-HT releasing 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 significant reductions in locomotor activity in animals assessed 2 and 13 days after pump implantation. 3. In a subsequent 14 day study that was designed to identify possible tolerance 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body weight gain compared to saline-infused controls; however, from day 7 onwards animals withdrawn from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 infusion periods. For 14-day treated animals this hypophagia was marked during the initial week of the study but only minor during the second week. In light of the sustained
drug effect on
body weight, the data suggest that
weight loss by
5-HT(2C) receptor stimulation may be only partly dependent on changes in food consumption and that
5-HT(2C) receptor agonists may have effects on thermogenesis. 5. These data suggest tolerance does not develop to the effects of d-
fenfluramine, mCPP and
Ro 60-0175 on rat
body weight gain.