Effect of SB 200646A,a 5-HT2C/5-HT2B receptor antagonist,in two conflict models of anxiety |
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Authors: | Kennett G A Bailey F Piper D C Blackburn T P |
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Institution: | (1) SmithKline Beecham, Coldharbour Road, The Pinnacles, CM19 5AD Harlow, Essex, UK |
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Abstract: | 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. |
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Keywords: | SB 200646A 5-HT2C 5-HT2B Anxiety Conflict models |
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