Involvement of 5-HT6 receptors in nigro-striatal function in rodents.
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.
Bourson
A
A
F. Hoffmann-La Roche Ltd., Preclinical Research, Pharma Division, Basle, Switzerland.
Boess
F G
FG
Bös
M
M
Sleight
A J
AJ
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D001552:Benzazepines / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced; D003024:Clozapine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051379:Mice; D016627:Oxidopamine / Q000494:pharmacology; D016548:Prosencephalon / Q000187:drug effects / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D018663:Adrenergic Agents; D001552:Benzazepines; D003024:Clozapine; D006220:Haloperidol; D016627:Oxidopamine; D011743:Pyrimidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C114163:Ro 4-6790; D000096926:Benzenesulfonamides; C097216:serotonin 6 receptor