ro-60-0175 and Body-Weight

Anxiety-like behavior resulting from repeated withdrawals from chronic ethanol diets is counteracted by systemic administration of a 5-HT2C receptor antagonist or a 5-HT1A receptor partial agonist.. This study investigated whether prior treatment with these agents into the amygdala, dorsal raphe nucleus, nucleus accumbens, or paraventricular nucleus during early withdrawals would ameliorate the social interaction deficits observed after a subsequent withdrawal.. Sprague-Dawley rats were exposed to three cycles of 5 days of forced ethanol diet (4.5%, w/v), with 2 days of control diet after the first and second cycles. Drugs were administered into one of four brain sites 4 h after removal of ethanol on the first and 2nd cycles but not the third. The social interaction test was performed 5 h after removal of ethanol on the third cycle. Drugs tested included SB-243213, a 5-HT2C receptor inverse agonist; buspirone, a 5-HT1A receptor partial agonist; and Ro 60 1075, a 5-HT2C receptor agonist.. Only SB-243213 (at 3 microg, but not at 1 and 0.3 microg) counteracted the social interaction deficits after injections into the amygdala, while buspirone (at 0.3 and 1 microg but not at 0.1 microg) reduced deficits only when given into the dorsal raphe nucleus. In contrast, the 5-HT2C receptor agonist, Ro 60 1075, accentuated the behavioral deficit after two weekly injections into the amygdala.. These results are consistent with the involvement of 5-HT2C receptors in the amygdala and 5-HT1A autoreceptors in the dorsal raphe nucleus in repeated ethanol withdrawal-induced sensitization of anxiety-like behavior.

Topics: Animals; Anxiety; Body Weight; Buspirone; Dose-Response Relationship, Drug; Ethanol; Ethylamines; Indoles; Nucleus Accumbens; Paraventricular Hypothalamic Nucleus; Pyridines; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT1A; Receptor, Serotonin, 5-HT2C; Serotonin 5-HT1 Receptor Agonists; Serotonin 5-HT2 Receptor Agonists; Serotonin Receptor Agonists; Substance Withdrawal Syndrome

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.

Topics: Analysis of Variance; Animals; Body Weight; Drinking; Eating; Ethylamines; Fenfluramine; Hypothalamus; Indoles; Infusion Pumps; Motor Activity; Piperazines; Rats; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin; RNA, Messenger; Serotonin Agents; Time Factors