Serotonergic and histaminergic mechanisms involved in intralipid drinking?

Abstract

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.

• Authors: Abegale W Hartfield, Nicholas A Moore, Peter G Clifton
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 76 Issue 2 Pg. 251-8 (Sep 2003) ISSN: 0091-3057 [Print] United States
• PMID: 14592676 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline
• Aminopyridines
• Dietary Fats
• Histamine H1 Antagonists
• Indoles
• Serotonin Antagonists
• Metergoline
• Cyproheptadine
• Serotonin
• Histamine
• Pyrilamine

Topics

• Aminopyridines (pharmacology)
• Animals
• Cyproheptadine (pharmacology)
• Dietary Fats (administration & dosage, pharmacology)
• Dose-Response Relationship, Drug
• Drinking Behavior (drug effects)
• Eating (drug effects)
• Histamine (physiology)
• Histamine H1 Antagonists (pharmacology)
• Hyperphagia (chemically induced, psychology)
• Indoles (pharmacology)
• Male
• Metergoline (pharmacology)
• Pyrilamine (pharmacology)
• Rats
• Serotonin (physiology)
• Serotonin Antagonists (pharmacology)