Involvement of 5‐HT6 receptors in nigro‐striatal function in rodents

• Published in: British journal of pharmacology Vol. 125; no. 7; pp. 1562 - 1566
• Main Authors: Bourson, Anne, Boess, Frank G, Bös, Michael, Sleight, Andrew J
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.1998; Nature Publishing
• Subjects: 5‐HT6 receptor; 6‐OHDA lesions; acetylcholine; Adrenergic Agents - pharmacology; Animals; Basal Ganglia Diseases - chemically induced; Benzazepines - pharmacology; Biological and medical sciences; catalepsy; Catalepsy - chemically induced; Clozapine - pharmacology; Corpus Striatum - drug effects; Corpus Striatum - physiology; dopamine; Haloperidol - pharmacology; Male; Medical sciences; Mice; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Oxidopamine - pharmacology; Pharmacology. Drug treatments; Prosencephalon - drug effects; Prosencephalon - physiology; Pyrimidines - pharmacology; Rats; Receptors, Serotonin - drug effects; Receptors, Serotonin - physiology; Ro 04‐6790; Serotonin Antagonists - pharmacology; Serotoninergic system; turning; Intraperitoneal administration; Brain stem; Rodentia; Central nervous system; Midbrain; Serotonine receptor; Biological activity; Vertebrata; Mammalia; Animal; Acetylcholine; Rotation behavior; Antagonist; Nigrostriatal pathway
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0702230

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