[Feeding disorders in 5-HT4 receptor knockout mice].
To study the functional contributions of the 5-HT4 receptor subtype of serotonin (5-HT), we have generated knockout mice lacking the 5-HT4 receptor gene. The male mutant mice exhibit a hyposensitivity to anorexic stress. Our recent data indicate that the pharmacological inactivation, using a systemic injection of the 5-HT4 receptor antagonist RS39604 (0.5 mg/kg), suppressed restraint stress-induced anorexia in wild-type female mice. In parallel, the same treatment reduced the 3,4-N-methylenedioxymethamphetamine (" ecstasy", 10 mg/kg)-induced anorexia in male wild-type mice. Our neurochemical analyses suggest that the mechanisms underlying feeding disorders in 5-HT4 receptor knockout mice are related to a lesser efficacy of 5-HT (hypothalamus, nucleus accumbens), leptin and the cocaine-amphetamine related transcript to reduce food intake following stress.
Compan
Valérie
V
Laboratoire de génomique fonctionnelle, UPR CNRS 2580, 141 rue de la Cardonille, 34094 Montpellier. Valerie.Compan@ccipe.cnrs.fr
Charnay
Yves
Y
Dusticier
Nicole
N
Daszuta
Annie
A
Hen
René
R
Bockaert
Joël
J
D000818:Animals; D000855:Anorexia / Q000209:etiology / Q000235:genetics / Q000517:prevention & control; D001066:Appetite / Q000187:drug effects / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D003345:Corticosterone / Q000502:physiology; D001068:Feeding and Eating Disorders / Q000235:genetics* / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects; D020738:Leptin / Q000096:biosynthesis / Q000235:genetics; D008032:Limbic System / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D010880:Piperidines / Q000494:pharmacology; D011407:Propane / Q000031:analogs & derivatives* / Q000494:pharmacology; D044422:Receptors, Serotonin, 5-HT4 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D012149:Restraint, Physical; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000502:physiology*; D058832:Serotonin 5-HT4 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D013315:Stress, Psychological / Q000150:complications / Q000503:physiopathology; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D020738:Leptin; D009419:Nerve Tissue Proteins; D010880:Piperidines; C475107:RS 39604; D058832:Serotonin 5-HT4 Receptor Antagonists; D012702:Serotonin Antagonists; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D011407:Propane; D003345:Corticosterone