On the elevated plus-maze the anxiolytic-like effects of the 5-HT1A agonist, 8-OH-DPAT, but not the anxiogenic-like effects of the 5-HT1A partial agonist, buspirone, are blocked by the 5-HT1A antagonist, WAY 100635

Abstract

In the present study we evaluated the effects of the 5-HT_1A receptor partial agonist, buspirone hydrochloride and the 5-HT_1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on the elevated plus-maze. In addition, the ability of the 5-HT_1A receptor antagonist, WAY 100635, to reverse the effects of both compounds was determined. 8-OH-DPAT (0.01–0.3 mg/kg, SC) dose-dependently increased the percent time on, and the number of entries to, the open arms of the maze. In a second experiment, WAY 100635 (0.003–0.3 mg/kg, SC) dose-dependently reversed the anxiolytic-like effects of 8-OH-DPAT (0.3 mg/kg, SC). In a third experiment, buspirone (0.3–4.0 mg/kg, SC) dose-dependently decreased the time spent on the open arms of the maze, indicating that it had anxiogenic-like effects. Buspirone also significantly decreased locomotor activity, which was evident in the decreases in the distance travelled on the open arms, closed arms and on the maze as a whole, the total number of arm entries and the mean speed of the animals. In contrast to its effects on 8-OH-DPAT-induced behaviours in the maze, WAY 100635 (0.003–1.0 mg/kg SC) failed to reverse any of the effects induced by buspirone. Animals treated with high doses of WAY 100635 (0.3–1.0 mg/kg SC) alone did not significantly differ from vehicle-treated animals on any of the measures recorded during elevated plus-maze trials. These data suggest that the anxiolytic-like effects of 8-OH-DPAT, but not the anxiogenic-like effects of buspirone, on the elevated plus-maze are mediated via 5-HT_1A receptors in the CNS.