Are 5-HT2 antagonists endowed with anxiolytic properties in rodents?

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Are 5-HT2 antagonists endowed with anxiolytic properties in rodents?

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Rhône-Poulenc Rorer, Centre de Recherches de Vitry-Alfortville, Vitry sur Seine, France. The precise role of serotonin (5-HT) in anxiety remains unclear. We report here on the effects of RP 62203, a new 5-HT2 antagonist, and ritanserin in different animal models of anxiety. In the elevated plus-maze in mice, RP 62203 increased dose-dependently the percentage of entries onto, and time spent on open arms, over the dose range 0.25-4 mg.kg-1 p.o. By contrast, ritanserin was ineffective up to the dose of 4 mg.kg-1 p.o. In addition, both compounds were tested against the anxiogenic compound FG 7142 (20 mg.kg-1, i.p.) in the plus-maze test in mice and via electrocorticographic recordings (ECoG) in rats. The anxiolytic effect of RP 62203 is antagonized by FG 7142 at a dose devoid of anxiogenic properties. A similar interaction between RP 62203 and FG 7142 is observed in ECoG studies. In contrast, ritanserin seemed to potentiate the anxiogenic and awakening activities of FG 7142. These results

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