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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.
Abstract:
The behavioural effects of 5-HT(2) receptor agonists, 5-HT(2A) and 5-HT(2C) receptor antagonists were investigated in the mouse four plates test (FPT), light/dark paradigm (L/D) and the elevated plus maze (EPM), in order to elucidate the role of the 5-HT(2) receptor subtypes in these models and to address the inconclusive results previously reported using rat psychopharmacological models. All compounds were administered intraperitoneally 30 min before each test. DOI, a preferential 5-HT(2A) agonist (0.5-8 mg/kg) and BW 723C86, a 5-HT(2B) agonist (8 and 16 mg/kg) provoked an anxiolytic-like response in the FPT. In the EPM, an anxiolytic-like effect was observed for DOI (0.5, 1 and 2 mg/kg), BW 723C86 (0.5, 4, 8 and 16 mg/kg), RO 60-0175 a 5-HT(2C) agonist (4 mg/kg) and the non-selective 5-HT(2) receptor agonist mCPP (0.25 mg/kg.). Ketanserin, a 5-HT(2A/2C) non-selective receptor antagonist (0.015 and 0.03 mg/kg), induced an anxiogenic-like effect in the L/D paradigm. The 5-HT(2C) antagonists (RS 10-2221, SDZ SER082 and SB 206553) were without effect in all three tests. These behavioural results are indicative of an anxiolytic-like action of 5-HT(2) receptor agonists, an anxiogenic-like effect of 5-HT(2A) receptor antagonism, whereas the blockade of 5-HT(2C) receptors are without effect in the mouse models studied.
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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