Antidepressant-like activity of ipsapirone, buspirone and gepirone in the forced swimming test in rats pretreated with proadifen

Abstract

The antidepressant-like activity of ipsapirone, buspirone and gepirone was studied in rats in the forced swimming test (behavioural despair test). lpsapirone and buspirone administered in single doses (5-20 mg/kg) did not affect the immobility time in this test. When administered in the same doses in a three-injection course in 24 h, buspirone was also inactive, while ipsapirone slightly but significantly reduced the immobility time only after a dose of 5 mg/kg. On the other hand, gepirone administered both in single doses (2.5-20 mg/kg) and in a three-injection course (5-20 mg/kg) potently and dose-dependently shortened the immobility time. 1-(2-Pyrimidinyl)-piperazine (1-PP; 5-20 mg/kg), a common metabolite of all the three drugs, administered in single doses or in a three-injection course, was inactive in the forced swimming test. In rats pretreated with proadifen (50 mg/kg), a non-selective drug metabolism inhibitor, both ipsapirone and buspirone administered in single doses (5-20 mg/kg) reduced the immobility time in a dose-dependent manner. Proadifen also potentiated the anti-immobility effect of gepirone (5 and 10 mg/kg). The anti-immobility effect of single doses (20 mg/kg) of ipsapirone, buspirone and gepirone in proadifen-pretreated animals was completely abolished by 1-PP (4 mg/kg). These results indicate that the antidepressant-like activity of the examined drugs in the behavioural despairtest is masked (ipsapirone, buspirone) or attenuated (gepirone) by their metabolite 1-PP.