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.
Hartfield
Abegale W
AW
Laboratory of Experimental Psychology, School of Biology, University of Sussex, Brighton, BN1 9QG, UK.
Moore
Nicholas A
NA
Clifton
Peter G
PG
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