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Characterizing the effects of 5-HT(2C) receptor ligands on motor activity and feeding behaviour in 5-HT(2C) receptor

Paul J Fletcher1, Maria Tampakeras, Judy Sinyard

  • 1Section of Biopsychology, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8. paul_fletcher@camh.net

Neuropharmacology
|June 9, 2009
PubMed

Insights

This study used 5-HT(2C) receptor knockout mice to evaluate the in vivo selectivity of various 5-HT(2C) receptor agonists and antagonists. Motor activity and food intake changes in knockout mice effectively screened these compounds, validating the approach.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Genetics

Background:

  • 5-HT(2C) receptor agonists show therapeutic promise but require in vivo selectivity data.
  • Locomotor activity and food intake are known behavioral effects of 5-HT(2C) receptor agonists.

Purpose of the Study:

  • To compare the in vivo potency and selectivity of various 5-HT(2C) receptor agonists and antagonists.
  • To establish the utility of 5-HT(2C) receptor knockout mice for screening these ligands.

Main Methods:

  • Compared agonists (mCPP, MK212, Ro 60-0175, WAY161503, CP809,101, lorcaserin) and antagonists (SB242084, SDZ SER 082) in wild-type and 5-HT(2C) receptor knockout mice.
  • Assessed effects on locomotor activity and food intake.

Main Results:

  • Agonists Ro 60-0175, CP809,101, and lorcaserin reduced activity and food intake in wild-type but not knockout mice, indicating 5-HT(2C) receptor selectivity.
  • Higher dose of Ro 60-0175 showed reduced selectivity in knockout mice.
  • Antagonist SB242084 increased activity in wild-type mice only, while SDZ SER 082 showed poor selectivity.

Conclusions:

  • Motor behavior and food intake studies in 5-HT(2C) receptor knockout mice provide a simple and effective in vivo method for screening 5-HT(2C) receptor ligands.
  • This approach aids in determining the selectivity of novel therapeutic compounds targeting the 5-HT(2C) receptor.

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