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 (H1 receptor antagonist), metergoline (5-HT(1/2) receptor antagonist), cyproheptadine (H1 and 5-HT(2A/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 H1 (mepyramine) or 5-HT(1/2) receptors (metergoline) alone was not sufficient to increase intake. Furthermore, combined blockade of H1 and 5-HT2C receptors (SB 242084 and mepyramine) was also insufficient to produce hyperphagia. Conversely, simultaneous blockade of H1, 5-HT(2A/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.
Laboratory of Experimental Psychology, School of Biology, University of Sussex, Brighton, BN1 9QG, UK.
Abegale W
AW
Hartfield
Nicholas A
NA
Moore
Peter G
PG
Clifton
D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D003533:Cyproheptadine / Q000494:pharmacology; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D006632:Histamine / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006963:Hyperphagia / Q000139:chemically induced / Q000523:psychology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology
C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D004041:Dietary Fats; D006634:Histamine H1 Antagonists; D007211:Indoles; D012702:Serotonin Antagonists; D008711:Metergoline; D003533:Cyproheptadine; D012701:Serotonin; D006632:Histamine; D011738:Pyrilamine