Abstract
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.
MeSH terms
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Animals
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Anorexia / etiology
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Anorexia / genetics
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Anorexia / prevention & control
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Appetite / drug effects
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Appetite / physiology
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Chromatography, High Pressure Liquid
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Corticosterone / physiology
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Feeding and Eating Disorders / genetics*
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Feeding and Eating Disorders / physiopathology
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Gene Expression Regulation / drug effects
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Leptin / biosynthesis
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Leptin / genetics
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Limbic System / drug effects
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Limbic System / physiopathology
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Male
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Mice
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Mice, Knockout
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N-Methyl-3,4-methylenedioxyamphetamine / toxicity
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Nerve Tissue Proteins / biosynthesis
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Nerve Tissue Proteins / genetics
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Piperidines / pharmacology
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Propane / analogs & derivatives*
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Propane / pharmacology
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Receptors, Serotonin, 5-HT4 / deficiency*
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Receptors, Serotonin, 5-HT4 / genetics
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Receptors, Serotonin, 5-HT4 / physiology
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Restraint, Physical
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Reverse Transcriptase Polymerase Chain Reaction
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Serotonin / physiology*
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Serotonin 5-HT4 Receptor Antagonists
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Serotonin Antagonists / pharmacology
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Stress, Psychological / complications
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Stress, Psychological / physiopathology
Substances
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Leptin
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Nerve Tissue Proteins
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Piperidines
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RS 39604
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Serotonin 5-HT4 Receptor Antagonists
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Serotonin Antagonists
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cocaine- and amphetamine-regulated transcript protein
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Receptors, Serotonin, 5-HT4
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Serotonin
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N-Methyl-3,4-methylenedioxyamphetamine
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Propane
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Corticosterone