COMPARISON OF THE ANTICONFLICT EFFECT OF BUSPIRONE AND ITS MAJOR METABOLITE 1-(2-PYRIMIDINYL)-PIPERAZINE (1-PP) IN RATS

The anxiolytic effects of buspirone and its major metabolite, 1-(2-pyr imidinyl)-piperazine (1-PP) have been investigated with a conflict (sh ock-induced suppression of drinking) paradigm in rats. Buspirone (10 m g/kg, p.o.) showed an anticonflict activity with a bell-shaped dose-re sponse relationship without any effect on spontaneous water consumptio n. Higher doses of buspirone reduced the punished response. Diazepam ( 20 and 40 mg/kg, yo) also showed an anticonflict activity in a dose-de pendent manner, but animals with diazepam showed an increase in sponta neous water consumption at these doses. On the other hand, 1-PP (6.25 - 200 mg/kg, p.o.) showed a weak anticonflict activity with a signific ant effect at 25 mg/kg without any effect on spontaneous water consump tion. In the 7-day treatment test, buspirone (5 and 10 mg/kg, p.o.), 1 -PP (5 and 25 mg/kg, p.o) and diazepam (10 and 40 mg/kg, p.o.) did not develop the tolerance to the anticonflict activity. Conversely, the a nticonflict activity of diazepam was increased by the repeated treatme nt. Diazepam (10 mg/kg, p.o.) showed an anticonflict activity without any effect on spontaneous water consumption in this test. These result s demonstrated that buspirone clearly exhibited an anticonflict effect similar to that of diazepam in a Vogel-type conflict test, and its re al anxiolytic effect may not be always based on 1-PP, the main metabol ite of buspirone.