Anxiolytic-like effects of 5-HT 2 ligands on three mouse models of anxiety

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.