5-HT4 receptor antagonism does not affect motor and reward mechanisms in the rat.
5-HT4 receptors are concentrated in areas of the brain which are rich in dopamine neuronal markers, which may suggest that they influence motor and reward processes. We tested this hypothesis by examining the effects of a 5-HT4 receptor antagonist, 8-amino-7-chloro-(N-butyl-4-piperidyl)methylbenzo-1,4-dioxan-5-car boxylate hydrochloride (SB-204070-A) on amphetamine- and nicotine-induced locomotor stimulation in intact rats. In rats with unilateral 6-hydroxydopamine-induced lesions of the ascending nigrostriatal dopaminergic projection, SB-204070-A was tested for its effects on amphetamine-induced rotation. SB-204070-A was also tested for its effects on rewarded behaviour maintained by intracranial self-stimulation. SB-204070-A did not alter behaviour under any of these conditions, suggesting a lack of involvement of the 5-HT4 receptor in motor and reward processes.
Reavill
C
C
Department of Neurobehavioral Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, UK.
Hatcher
J P
JP
Lewis
V A
VA
Sanger
G J
GJ
Hagan
J
J
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology*; D006948:Hyperkinesis / Q000139:chemically induced; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012653:Self Stimulation / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology*
D004146:Dioxanes; D010880:Piperidines; D012702:Serotonin Antagonists; C084858:SB 204070A; D009538:Nicotine; D000661:Amphetamine; D003042:Cocaine