cp-94253 and 1-(3-trifluoromethylphenyl)piperazine

To clarify the role of the 5-HT system in limbic outputs, the present study compared the effects of the 5-HT1A agonist 8-OH-DPAT and the 5-HT1B agonist CP-94253 with the non-selective 5-HT agonist TFMPP on the firing rate of ventral pallidal (VP) neurons recorded in chloral hydrate-anesthetized rats. 8-OH-DPAT (0.25-256 microg/kg i.v.) dose-dependently enhanced (9/26 neurons) or suppressed (8/26) activity, and the 5-HT1A antagonist (+)WAY-100135 often attenuated these responses. TFMPP (0.011-1.453 mg/kg i.v.) dose-dependently reduced the firing rate of 7/8 VP neurons tested. In contrast, CP-94253 (0.013-12.8 mg/kg i.v.) had little or no effect. In sum, these data suggest that the 5-HT1A receptor appears to be particularly important in influencing limbic outputs mediated via the VP.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Action Potentials; Animals; Dose-Response Relationship, Drug; Globus Pallidus; Male; Neurons; Piperazines; Pyridines; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT1B; Receptors, Serotonin; Receptors, Serotonin, 5-HT1; Serotonin Antagonists; Serotonin Receptor Agonists

The effects of serotonin (5-hydroxytryptamine, 5-HT)(1/2) receptor agonists for 5-HT(1) and 5-HT(2) receptors on dark-phase ingestive behavior were evaluated 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, IP: 5-HT(1A) and 3-30, respectively], CP-94,253 (5-HT(1B); 0.3-3), TFMPP (5-HT(1B/2C); 0. 3-10), m-CPP (5-HT(2C/1B); 0.3-10), ORG 37684 (5-HT(2C); 0.3-10), BW 723C86 (5-HT(2B); 3-30) and DOI (5-HT(2A/2C); 0.3-3). Ipsapirone induced hyperphagia during the first hour of food access and hypophagia during the last interval. All other compounds induced dose- and time-dependent hypophagia. m-CPP and TFMPP induced the most marked reduction of food intake and were the only drugs inducing rebound hyperphagia. Except for m-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-HT(1B), 5-HT(2C), 5-HT(2A) or 5-HT(2B) receptors results in hypophagia. As the less selective agonists were the more potent anorexics, it is suggested that simultaneous activation of these receptors results in synergistic effects on ingestive behavior. Additional antagonism studies are required to ascertain the proposed role of particular 5-HT receptor subtypes in the hypophagic effects of the tested compounds.

Topics: Amphetamines; Animals; Darkness; Dose-Response Relationship, Drug; Drinking; Drinking Behavior; Eating; Feeding Behavior; Female; Indoles; Piperazines; Pyridines; Pyrimidines; Rats; Rats, Wistar; Receptors, Serotonin; Receptors, Serotonin, 5-HT1; Serotonin Receptor Agonists; Thiophenes; Time Factors