Serotonergic and histaminergic mechanisms involved in intralipid drinking?

Some newer antipsychotic agents are associated with weight gain in humans and a hyperphagic response to intralipid solutions in rodents, To examine the possible contribution of serotonin (5-HT) and histamine (H) receptor blockade in antipsychotic-associated hyperphagia, rats were trained to drink a palatable, high-calorie fat emulsion (10% intralipid) during 30-min sessions and were tested following pretreatment with mepyramine (H-1 receptor antagonist), metergoline (5-HT1/2 receptor antagonist), cyproheptadine (H-1 and 5-HT2A/2B/2C and muscarinic receptor antagonist), SB 242084 (5-HT2C receptor antagonist) and an SB 242084-mepyramine combination. Total intake and ingestive behaviour microstructure were measured. Mepyramine (10 mg/kg) reduced intake, as did metergoline (3.0 mg/kg). Cyproheptadine (0.1 - 1.0 mg/kg) increased intake and microstructural analysis suggests that this was due to increased numbers of clusters of licking. SB 242084 (3 mg/kg) reduced intake, either when administered alone, or in combination with mepyramine (1 mg/kg). In conclusion, simple antagonism of either H-1 (mepyramine) or 5-HT1/2 receptors (metergoline) alone was not sufficient to increase intake. Furthermore, combined blockade of H, and 5-HT2C receptors (SB 242084 and mepyramine) was also insufficient to produce hyperphagia. Conversely, simultaneous blockade of H-1, 5-HT2A/2C and muscarinic receptors (cyproheptadine) led to a substantial hyperphagia and pattern of ingestive behaviour that was similar to that previously observed with some newer antipsychotic agents. (C) 2003 Elsevier Inc. All rights reserved.