Hyperactivity and reduced energy cost of physical activity in serotonin 5-HT2C receptor mutant mice

Katsunori Nonogaki, Luna Abdallah, Evan H. Goulding, Stephen J. Bonasera, Laurence H. Tecott*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

90 Scopus citations


We have observed late-onset obesity in mutant mice lacking the serotonin 5-HT2c receptor. Despite chronically elevated food intake, young adult mutants exhibit neither elevated adiposity nor altered glucose or fat homeostasis. However, obesity subsequently develops after 6 months of age without increases in their level of hyperphagia. In this study, we investigated determinants of energy expenditure in 5-HT2c receptor mutant mice. Young adult mutants displayed patterns of elevated activity levels that were enhanced by fasting and tightly associated with repeated visits to a food source. Surprisingly, subsequent obesity development occurred despite persisting locomotor hyperactivity and without age-related declines in resting metabolic rate. Rather, substantial reductions in the energy cost of locomotor activity (LA) were observed in 5-HT2c receptor mutant mice. Moreover, both mutant and wild-type mice displayed age-related declines in the energy cost of LA, indicating that this process may be regulated by both aging and serotonergic signaling. These results indicate that a mutation of the 5-HT2c receptor gene (htr2c) increases LA, which contributes to the maintenance of normal body composition in young adult mutants despite their hyperphagia. Moreover, age-dependent reductions in the energy cost of physical activity could contribute to the subsequent development of late-onset obesity in 5-HT2c receptor mutant mice.

Original languageEnglish (US)
Pages (from-to)315-320
Number of pages6
Issue number2
StatePublished - Feb 1 2003

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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