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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Evidence that RU 24969-induced locomotor activity in C57/B1/6 mice is specifically mediated by the 5-HT1B receptor.

1. The behavioural effects of the 5-HT1B receptor agonists, RU 24969 and CGS 12066B, have been investigated in C57/B1/6 mice. 2. RU 24969 (1-30 mg kg-1) produced intense and prolonged hyperlocomotion and other behavioural changes. 3. CGS 12066B caused similar effects, but they were much less pronounced, inconsistent and transient irrespective of whether this drug was given i.p. (1-15 mg kg-1) or i.c.v. (0.2-40 micrograms). However, CGS 12066B (7.5 and 15 mg kg-1) caused a dose-related inhibition of RU 24969 (7.5 mg kg-1)-induced hyperlocomotion indicating that the former is a 5-HT1B partial agonist. 4. RU 24969 (7.5 mg kg-1 i.p.)-induced hyperlocomotion was inhibited by the (-)-, but not (+)-isomers of pindolol (4 mg kg-1) and propranolol (20 mg kg-1) but not by metoprolol (10 mg kg-1) or ICI 118,551 (5 mg kg-1), consistent with an involvement of 5-HT1A or 5-HT1B receptors. 5. The response was not altered by the selective 5-HT1A receptor antagonist, WAY 100135 (5 mg kg-1, s.c.), the 5-HT2A/5-HT2C receptor antagonist, ritanserin (0.1 mg kg-1), the selective 5-HT3 receptor antagonist, ondansetron (1 mg kg-1) or the non-selective 5-HT receptor antagonists methysergide (3 mg kg-1) and metergoline (3 mg kg-1). 6. Although spiroxatrine (0.1 mg kg-1) and ketanserin (1 mg kg-1) inhibited RU 24969-induced hyperlocomotion, these effects were probably due to antagonism of dopamine D2 receptors and alpha 1-adrenoceptors respectively.(ABSTRACT TRUNCATED AT 250 WORDS)[1]


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