Anxiolytic-like effects of 5-HT2 ligands on three mouse models of anxiety

Bríd Aine Nic Dhonnchadha1, Michel Bourin, Martine Hascoët

  • 1EA 3256 Neurobiologie de l'Anxiété et de la Dépression, Laboratoire Pharmacologie et GIS Medicament, Faculté Médecien et GIS Medicament, BP 53508, 1 rue Gaston Veil, F44035 Nantes, Cedex 01, France.

Insights

Serotonin 5-HT(2) receptor agonists showed anxiolytic effects, while 5-HT(2A) receptor antagonism induced anxiety-like behavior in mice. 5-HT(2C) receptor blockade had no effect in these anxiety models.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Behavioral Science

Background:

  • The role of serotonin 5-HT(2) receptor subtypes in anxiety remains unclear due to conflicting results in rat models.
  • Investigating these receptors in mouse models offers a new perspective on their function in anxiety-related behaviors.

Purpose of the Study:

  • To elucidate the specific roles of 5-HT(2A), 5-HT(2B), and 5-HT(2C) receptor subtypes in anxiety-like behaviors using established mouse models.
  • To clarify the inconclusive findings from previous rat studies by examining 5-HT(2) receptor pharmacology in mice.

Main Methods:

  • Utilized three established behavioral tests for anxiety in mice: the four plates test (FPT), light/dark paradigm (L/D), and elevated plus maze (EPM).
  • Administered various 5-HT(2) receptor agonists (DOI, BW 723C86, RO 60-0175, mCPP) and antagonists (Ketanserin, RS 10-2221, SDZ SER082, SB 206553) intraperitoneally 30 minutes prior to testing.

Main Results:

  • 5-HT(2A) and 5-HT(2B) receptor agonists (DOI, BW 723C86) demonstrated anxiolytic-like effects in the FPT and EPM.
  • A non-selective 5-HT(2) agonist (mCPP) and a 5-HT(2C) agonist (RO 60-0175) also exhibited anxiolytic-like effects in the EPM.
  • Ketanserin, a 5-HT(2A/2C) antagonist, induced an anxiogenic-like effect in the L/D paradigm, while 5-HT(2C) antagonists were ineffective across all tests.

Conclusions:

  • Serotonin 5-HT(2) receptor agonists possess anxiolytic-like properties in mouse models of anxiety.
  • Antagonism at the 5-HT(2A) receptor appears to promote anxiety-like behavior.
  • Blockade of 5-HT(2C) receptors does not influence anxiety-like behaviors in the mouse models investigated.

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