Effect of SB 200646A, a 5-HT2C/5-HT2B receptor antagonist, in two conflict models of anxiety.
SB 200646A is the first selective 5-HT2C/5-HT2B receptor antagonist and has previously been observed to have anxiolytic-like properties in the rat social interaction test. In the present study the effects of the compound in two conflict models of anxiety, the rat Geller-Seifter and marmoset conflict test, were examined. In the rat Geller-Seifter test, suppressed responding was increased by all doses of SB 200646A between 5 and 40 mg/kg PO when given 1 h pretest. Unsuppressed responding was slightly increased only at 10 mg/kg PO. Suppressed responding was also increased by the benzodiazepine anxiolytic, chlordiazepoxide, at 1, 2.5 and 5 mg/kg PO 1 h pretest. Unsuppressed responding was modestly increased by chlordiazepoxide only at 5 mg/kg PO. In the marmoset conflict test marmosets were trained to lever press for a palatable food reward. Lever pressing was subsequently suppressed by air puffs. In this procedure suppressed responding was increased by both the benzodiazepine anxiolytic diazepam at 2 and 5 mg/kg PO and SB 200646A after 10 and 20 mg/kg PO. Both treatments caused small increases in unsuppressed responding at 2 and 20 mg/kg PO respectively. Taken together with the previous effects of SB 200646A in the rat social interaction test, this is compelling evidence that 5-HT2C/2B receptor antagonists may possess anxiolytic properties.
Kennett
G A
GA
SmithKline Beecham, Harlow, Essex, UK.
Bailey
F
F
Piper
D C
DC
Blackburn
T P
TP
D000818:Animals; D001007:Anxiety / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects*; D002707:Chlordiazepoxide / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D003220:Conflict, Psychological; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D007398:Interpersonal Relations; D008297:Male; D008960:Models, Psychological; D051381:Rats; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
D007211:Indoles; D012702:Serotonin Antagonists; C080864:N-(1-methyl-5-indolyl)-N'-(3-pyridyl)urea; D002707:Chlordiazepoxide; D014508:Urea; D003975:Diazepam