RU24969-induced behavioural syndrome requires activation of both 5HT1A and 5HT1B receptors.
The behavioural profiles of the mixed 5HT(1A/B) agonist RU24969 and the more selective 5HT1B agonist anpirtoline were compared. Both compounds induce an increase in activity as measured in photocell activity cages. The behaviours displayed by the rats receiving each treatment differed markedly, with RU24969 inducing flat body posture and circling of the cage perimeter (1.25-10 mg/kg S.C.), whereas anpirtoline increased ambulation characterised by a hopping motion (1.25-5.0 mg/kg S.C.). The effects of RU24969 were attenuated by both the 5HT1A antagonist WAY100635 (0.03 1.25 mg/kg S.C.) and the 5HT(1B/D) antagonist GR127935 (1.0-5.0 mg/kg S.C.). Anpirtoline-induced behaviour was attenuated by GR127935 across the same dose range but was largely unaffected by WAY100635 even at doses above those which had blocked the effects of RU24969. Coadministration of the selective 5HT1A agonist 8-OH-DPAT (0.03-1.25 mg/kg S.C.) with anpirtoline (2.5 mg/kg) induced a dramatic increase in locomotor activity and a behavioural syndrome identical to that produced by RU24969. Thus it would appear that a synergistic effect of stimulation of both 5HT1A and 5HT1B receptors underlies the behavioural effects of RU24969, while anpirtoline acts mainly via stimulation of 5HT1B receptors only.
O'Neill
M F
MF
Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey, UK.
Parameswaran
T
T
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects
D007211:Indoles; D010880:Piperidines; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; C075631:anpirtoline; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin