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

Abstract

1 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 uid (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 e ect 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. 2 Ro 04-6790 (3, 10 and 30 mg kg 71 i.p.) did not induce catalepsy and had no e ect on catalepsy induced by either haloperidol or SCH 23390. 3 Ro 04-6790 (3, 10 and 30 mg kg 71 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 a ect the rotational behaviour induced by either L-Dopa or amphetamine. 4 5-HT 6 receptor antagonism inhibited the rotational behaviour of 6-OHDA lesioned rats induced by treatment with the muscarinic antagonists scopolamine and atropine. 5 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.

Endogenous Serotonin Excites Striatal Cholinergic Interneurons via the Activation of 5-HT 2C, 5-HT6, and 5-HT7 Serotonin Receptors: Implications for Extrapyramidal Side Effects of Serotonin Reuptake Inhibitors

“…Compelling evidence suggests that 5-HT modulates cholinergic signalling in several brain areas (Cassel and Jeltsch, 1995;Bourson et al, 1998). Depending upon the specific region involved, this functional interaction may powerfully influence cognitive functions as well as motor activity.…”

Ionotropic Glutamate Receptor Modulation of 5-HT6 and 5-HT7 mRNA Expression in Rat Brain

“…Consistent with this speculation, behavioral studies suggest that 5-HT 6 receptors mediate a circumscribed behavioral pattern that requires an intact (Values are expressed as mean optical density for CA2 and CA3 Ϯ SEM for 10 animals.) cholinergic system (Bourson et al 1995;Bourson et al 1998). Furthermore, aniracetam has been shown to modulate cholinergic systems (Bartolini et al 1992;Pepeu and Spignoli 1989).…”

The pipeline and future of drug development in schizophrenia

“…97 Studies in rodents have suggested a role for 5-HT 6 receptors in the control of cholinergic neurotransmission, 98 and the selective 5-HT 6 receptor antagonist SB-271046 has been shown to improve memory retention in the water maze test of spatial learning and memory. 99 Thus, 5-HT 6 receptors may have an important future role in the treatment of cognitive deficits in neuropsychiatric illnesses such as Alzheimer's disease and schizophrenia.…”