Effects of serotonin(1/2) receptor agonists on dark-phase food and water intake in rats

The effects of serotonin (5-hydroxytryptamine, 5-HT)(1/2) receptor agonists for 5-HT1 and 5-HT2 receptors on dark-phase ingestive behavior were evalua ted in 12-h food-deprived, female Wistar rats. The amount of food and water consumed after 1, 2, 6 and 12 h was measured. The following agonists were tested: ipsapirone [preferred 5-HT receptor(s) and dose range in mg/kg, IF: 5-HT1A and 3-30, respectively], CP-94,253 (5-HT1B; 0 3-3), TFMPP (5-HT1B/2 C; 0.3-10), m-CPP (5-HT2C/1B; 0.3-10), ORG 37684 (5 -HT2C; 0.3-10), BW 723C 86 (5-HT2B; 3-30) and DOI (5-HT2A/2C; 0.3-3). Ipsapirone induced hyperphagi a during the first hour of food access and hypophagia during the last inter val. All other compounds induced dose- and time-dependent hypophagia. m-CPP and TFMPP induced the most marked reduction of food intake and were the on ly drugs inducing rebound hyperphagia. Except for In-CPP and TFMPP, effects on food intake could generally be dissociated from effects on water intake . The receptor profile of the compounds tested suggests that stimulation of 5 -HT1B, 5-HT2C, 5 -HT2A or 5-HT2B receptors results in hypophagia. As the less selective agonists were the more potent anorexics, it is suggested th at simultaneous activation of these receptors results in synergistic effect s on ingestive behavior. Additional antagonism studies are required to asce rtain the proposed role of particular 5-HT receptor subtypes in the hypopha gic effects of the tested compounds. (C) 2000 Elsevier Science Inc. All rig hts reserved.