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4‐Amino‐N‐(2,4 bis‐methylamino‐pyrimidin‐4‐yl) benzene sulphonamide (Ro 04‐6790) is a potent, selective and competitive antagonist for the 5‐HT6 receptor which can be detected in the cerebro‐spinal fluid (CSF) of rats following intraperitoneal administration. Since 5‐HT6 receptor mRNA and 5‐HT6 receptor‐like immunoreactivity have been shown to be present in the striatum, the purpose of the present study was to evaluate the effect of 5‐HT6 receptor antagonism on haloperidol‐ and SCH 23390‐induced catalepsy in mice and on the turning behaviour of rats with unilateral 6‐hydroxydopamine (6‐OHDA) lesions of the medial forebrain bundle. Ro 04‐6790 (3, 10 and 30 mg kg−1 i.p.) did not induce catalepsy and had no effect on catalepsy induced by either haloperidol or SCH 23390. Ro 04‐6790 (3, 10 and 30 mg kg−1 i.p.) did not itself induce rotational behaviour in rats with unilateral 6‐hydroxydopamine (6‐OHDA) lesions of the medial forebrain bundle nor did it affect the rotational behaviour induced by either L‐Dopa or amphetamine. 5‐HT6 receptor antagonism inhibited the rotational behaviour of 6‐OHDA lesioned rats induced by treatment with the muscarinic antagonists scopolamine and atropine. The data support earlier conclusions from experiments with antisense oligonucleotides that the 5‐HT6 receptor is involved in the control of acetylcholine neurotransmission in the rat brain. British Journal of Pharmacology (1998) 125, 1562–1566; doi:10.1038/sj.bjp.0702230
British Journal of Pharmacology – Wiley
Published: Dec 1, 1998
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