Effects of the 5-HT2B receptor agonist, BW 723C86, on three rat models of anxiety.
1. BW 723C86 (3 and 10 mg kg-1, s.c. 30 min pretest), a 5-HT2B receptor agonist, increased total interaction, but not locomotion in a rat social interaction test, a profile consistent with anxiolysis. 2. The effect of BW 723C86 in the social interaction test is likely to be 5-HT2B receptor-mediated as it was prevented by pretreatment with the 5-HT2C/2B receptor antagonist, SB 200646A, (1 and 2 mg kg-1, p.o., 1 h pretest) which did not affect basal levels of social interaction at the doses used. 3. An anxiolytic-like action was also observed in the rat Geller-Seifter conflict test, where BW 723C86 (0.5-50 mg kg-1, s.c. 30 min pretest) modestly, but significantly increased punished, but not unpublished responding. 4. In a rat 5 min elevated x-maze test, BW 723C86 (1-10 mg kg-1, s.c.) had no significant effect. 5. The maximal anxiolytic-like effect of BW 723C86 approached that of the benzodiazepine anxiolytic, chloradiazepoxide (5 mg kg-1, s.c. 30 min pretest) in the social interaction test, but was markedly less in the Geller-Siefter test. The effect of BW 723C86 was also clearly less than chlordiazepoxide in the elevated x-maze procedure where it had no significant effect. 6. In conclusion, BW 723C86 exerted an appreciable anxiolytic-like profile in a rat social interaction test, but had a weaker effect in the Geller-Siefter and was ineffective in the elevated x-maze test used. These effects are likely to be 5-HT2B receptor-mediated.
Kennett
G A
GA
Psychiatry Department, SmithKline Beecham Pharmaceuticals, Harlow, Essex.
Bright
F
F
Trail
B
B
Baxter
G S
GS
Blackburn
T P
TP
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects*; D002707:Chlordiazepoxide / Q000494:pharmacology; D004195:Disease Models, Animal; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
C092430:1-(5-(2-thenyloxy)-1H-indol-3-yl)propan-2-amine; D014151:Anti-Anxiety Agents; D007211:Indoles; D017366:Serotonin Receptor Agonists; D013876:Thiophenes; C080864:N-(1-methyl-5-indolyl)-N'-(3-pyridyl)urea; D002707:Chlordiazepoxide; D014508:Urea