GR-127935 BLOCKS THE LOCOMOTOR AND ANTIDEPRESSANT-LIKE EFFECTS OF RU-24969 AND THE ACTION OF ANTIDEPRESSANTS IN THE MOUSE TAIL SUSPENSION TEST

The 5-HT1A/B agonist RU 24969 induces hyperactivity in rodents and als o shows antidepressant like effects in some animal models of depressio n. We have examined the effects of selective antagonists at 5-HT1A and 5-HT1B/D receptors (WAY 100135 and GR 127935, respectively) on both t he hyperlocomotor and anti-immobility effects of RU 24969. While a hig h dose of WAY 100135 (10 mg/kg) had no effect in either paradigm, GR 1 27935 attenuated the behavioural effects of RU 24969 in both. WAY 1001 35 was also without effect on the antidepressant effect of paroxetine, while GR 127935 blocked the effects of paroxetine (1 mg/kg) and imipr amine (10 mg/kg). Furthermore, while coadministration of paroxetine or imipramine enhanced the effects of RU 24969 in the mouse tail suspens ion test, imipramine had no effect on the locomotor activating effects of the 5-HT1B agonist, suggesting different neural substrates may und erly the effects in the different tests. These studies indicate a role for the 5-HT1B/D receptor in the mediation of the effects of antidepr essant treatment.