The novel buspirone analogue, 8-[4-[2-(1,2,3,4-tetrahydroisoquinolinyl)]butyl]-8-azaspiro[4.5]decane-7,9-dione, with anxiolytic-like and antidepressant-like effects in rats

In the conflict drinking test, used as a model to examine anxiolytic-like a ctivity, the novel buspirone analogue 8-[4-[2-(1,2,3,4-tetrahydroisoquinoli nyl)]butyl)-8-azaspiro[4.5] decane-7,9-dione (MM199) (0.62-2.5 mg/kg) and b uspirone (0.62-5 mg/kg), significantly increased the punished drinking in w ater-deprived rats, without affecting water consumption or perception of th e stimulus. The anticonflict activity of MM199 (1.25 mg/kg) was blocked by (S)-WAY 100135 (20 mg/kg), a 5-hydroxytrypatmine(1A) (5-HT1A) receptor anta gonist. In the forced swimming test, used as a model to examine the antidep ressant-like activity, MM199 (5-20 mg/kg) reduced the immobility time, whil e buspirone (5-20 mg/kg) had no such effect. The reduced immobility induced by MM199 (20 mg/kg) was antagonized by (S)-WAY100135 (10 mg/kg). The above findings suggest that MM199 possesses potent anxiolytic- and antidepressan t-like properties which are mediated by activation of 5-HT1A receptors.