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

E. Przegaliski

Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, Kraków, PL 31-343 Poland

E. Tatarczyska

Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, Kraków, PL 31-343 Poland

E. Chojnacka-Wójcik

Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, Kraków, PL 31-343 Poland

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.

Journal of Psychopharmacology, Vol. 4, No. 4, 204-209 (1990)
DOI: 10.1177/026988119000400404


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