Inhibitory effect of 5-hydroxytryptamine on hyperphagia in mice with genetic overexpression of neuropeptide Y.
The present study examined the effect of 5-hydroxytraptamine (5-HT) on the feeding behavior of transgenic mice with neuropeptide Y (NPY) overexpression. Solution of 5-HT (1, 2.5 or 5 mg/kg) was administered intraperitoneally into (1) NPY-overexpressing mice, and (2) wild-type mice with 2-deoxy-d-glucose (2-DG) induced hyperphagia. The NPY-overexpressing mice were further divided into five groups: (1) control mice, (2) mice treated with 5-HT (5 mg/kg), (3) mice treated with 5-HT (5 mg/kg) and ketanserin (0.5 or 1 mg/kg), a 5-HT2A receptor antagonist, (4) mice treated with insulin (1 IU/kg), and (5) mice treated with insulin (1 IU/kg) and 5-HT (5 mg/kg). Food intake and plasma glucose levels were measured. The results showed that 5-HT reduced hyperphagia in both NPY-overexpressing mice and 2-DG-treated mice in dose-dependent manner. Hyperglycemia was induced by 5-HT administration. Ketanserin antagonized the 5-HT induced hypophagia and hyperglycemia. Insulin, on the other hand, prevented 5-HT induced hyperglycemia but not the hypophagic effect. In conclusion, 5-HT reduces hyperphagia in the NPY-overexpressing rat through action on 5-HT2A receptors and this hypophagic effect of 5-HT does not depend on the hyperglycemia.
Hsiao
Sheng-Huang
SH
Department of Neurosurgery, Taiepi City Hospital, Taipei City 10601, Taiwan.
Chung
Hsien-Hui
HH
Inui
Akio
A
Tong
Yat-Ching
YC
Cheng
Juei-Tang
JT
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D003847:Deoxyglucose / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D006963:Hyperphagia / Q000188:drug therapy* / Q000235:genetics* / Q000523:psychology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009478:Neuropeptide Y / Q000235:genetics* / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D000963:Antimetabolites; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D009478:Neuropeptide Y; D012702:Serotonin Antagonists; D012701:Serotonin; D007650:Ketanserin; D003847:Deoxyglucose