Cyamemazine as an anxiolytic drug on the elevated plus maze and light/darkparadigm in mice

Several studies have demonstrated that cyamemazine, a classic antipsychotic compound, possesses anxiolytic properties in humans as well as a potent an tagonistic effect on 5-HT2C and 5-HT3 receptors. In this study the level of anxiety of mice was assessed in the light/dark exploration test and the el evated plus maze (EPM) following both acute and chronic administration. Spo ntaneous locomotor activity was measured using a photoelectric actimeter. A cute or chronic administration of cyamemazine dramatically decreases the sp ontaneous locomotor activity of mice at the dose of I mg/kg in comparison w ith the control group. In the light/dark exploration test, cyamemazine (0.3 75 mg/kg) only demonstrated anxiolytic-like activity following acute admini stration. In the elevated plus maze (EPM), cyamemazine did not induce any a nxiolytic like effects after acute administration. However, after chronic a dministration, cyamemazine at doses of 0.25, 0.375, 0.5 and 1 mg/kg signifi cantly increased the time spent in the open arms. The number of open arm en tries was also increased at 0.25 and 0.5 mg/kg. Various serotonergic ligand s were then used to examine the role of the various receptors in mediating the effects of cyamemazine in the EPM. Concerning the 5-HT2 ligands DOI and mCPP antagonised the effects of cyamemazine and N-desmethyl clozapine pote ntiated the effects. For 2-methyl-5-HT and ondansetron, the 5-HT3 receptor ligands did not seem to have any effect. It appears that the 5-HT2C recepto rs are more implicated in the function of mediating the anxiolytic effect o f cyamemazine in the EPM. The discrepancy of results obtained in the tests, following acute or chronic administration could be the result of the combi ned activity of dopamine D-2 receptor antagonism with antagonism of 5-HT2C and 5-HT3 receptors. (C) 2001 Elsevier Science B.V. All rights reserved.