Fluvoxamine exerts anorexic effect in 5-HT2C receptor mutant mice with heterozygous mutation of beta-endorphin gene

Area of Science:

• Neuroscience
• Pharmacology
• Genetics

Background:

• Serotonin (5-hydroxytryptamine; 5-HT) 2C receptors and melanocortin pathways are implicated in appetite regulation.
• Selective serotonin reuptake inhibitors (SSRIs) like fluvoxamine can influence feeding behavior.
• Previous research suggests 5-HT2C receptor inactivation combined with SSRIs can suppress feeding via 5-HT1B receptor activation.

Purpose of the Study:

• To investigate the mechanisms underlying fluvoxamine-induced anorexia.
• To determine the roles of serotonin 2C receptors, beta-endorphin, and proopiomelanocortin (POMC) in feeding suppression.
• To compare the anorectic effects of fluvoxamine and m-chlorophenylpiperazine (mCPP) in genetically modified mice.

Main Methods:

• Utilized 5-HT2C receptor mutant mice and mice with heterozygous mutation of the beta-endorphin gene (2CREnd mice).
• Administered fluvoxamine and mCPP to assess effects on food intake in different mouse models.
• Measured hypothalamic proopiomelanocortin (POMC) expression in relation to drug effects.

Main Results:

• Fluvoxamine induced anorexia in 2CREnd mice but not in wild-type or 5-HT2C receptor mutant mice with reduced POMC expression.
• mCPP suppressed food intake across all tested groups: 5-HT2C receptor mutant mice, 2CREnd mice, and wild-type mice.
• Fluvoxamine's anorectic effect was dependent on intact 5-HT2C receptor signaling, beta-endorphin, and functional POMC activity.

Conclusions:

• Fluvoxamine-mediated feeding suppression necessitates intact 5-HT2C receptor, beta-endorphin signaling, and hypothalamic POMC activity.
• mCPP-induced anorexia is less dependent on these specific pathways, suggesting alternative mechanisms of action.
• These findings highlight distinct neurobiological pathways for different serotonergic drugs influencing appetite.