RU24969 INDUCED BEHAVIORAL SYNDROME REQUIRES ACTIVATION OF BOTH 5HT(1A) AND 5HT(1B) RECEPTORS

The behavioural profiles of the mixed 5HT(1A/B) agonist RU24969 and th e more selective 5HT(1B) agonist anpirtoline were compared. Both compo unds induce an increase in activity as measured in photocell activity cages. The behaviours displayed by the rats receiving each treatment d iffered markedly, with RU24969 inducing flat body posture and circling of the cage perimeter (1.25-10 mg/kg SC), whereas anpirtoline increas ed ambulation characterised by a hopping motion (1.25-5.0 mg/kg SC). T he effects of RU24969 were attenuated by both the 5HT(1A) antagonist W AY 100635 (0.03-1.25 mg/kg SC) and the 5HT(1B/D) antagonist GR127935 ( 1.0-5.0 mg/kg SC). Anpirtoline-induced behaviour was attenuated by GR1 27935 across the same dose range but was largely unaffected by WAY1006 35 even at doses above those which had blocked the effects of RU24969. Coadministration of the selective 5HT(1A) agonist 8-OH-DPAT (0.03-1.2 5 mg/kg SC) with anpirtoline (2.5 mg/kg) induced a dramatic increase i n locomotor activity and a behavioural syndrome identical to that prod uced by RU24969. Thus it would appear that a synergistic effect of sti mulation of both 5HT(1A) and 5HT(1B) receptors underlies the behaviour al effects of RU24969, while anpirtoline acts mainly via stimulation o f 5HT(1B) receptors only.