Premium
Involvement of 5‐HT 6 receptors in nigro‐striatal function in rodents
Author(s) -
Bourson Anne,
Boess Frank G,
Bös Michael,
Sleight Andrew J
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702230
Subject(s) - catalepsy , medial forebrain bundle , sch 23390 , haloperidol , muscarinic acetylcholine receptor , endocrinology , medicine , acetylcholine , receptor , chemistry , pharmacology , antagonist , cholinergic , neuroscience , striatum , psychology , dopamine
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‐HT 6 receptor which can be detected in the cerebro‐spinal fluid (CSF) of rats following intraperitoneal administration. Since 5‐HT 6 receptor mRNA and 5‐HT 6 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‐HT 6 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‐HT 6 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‐HT 6 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