Investigation of stretching behaviour induced by the selective 5‐HT₆ receptor antagonist, Ro 04–6790, in rats

Abstract

1 The present study examined the eects of the selective 5-HT 6 receptor antagonist 4-amino-N-(2, 6 bis-methylamino-pyrimidin-4-yl)-benzene sulphonamide (Ro 04-6790) on locomotor activity and unconditioned behaviour in male Sprague Dawley rats (230 ± 300 g). , i.p.) was signi®cantly greater than that observed in saline-treated rats. The yawning behaviour, however, was not dose-dependent nor was the number of yawns in any of the drug treated groups signi®cantly greater than in those treated with saline. 6 These data suggest that systemic injection of the 5-HT 6 antagonist, Ro 04-6790, produces a stretching behaviour that appears to be mediated by an increase in cholinergic neurotransmission in the CNS and which could be a useful functional correlate for 5-HT 6 receptor blockade. There is no evidence for dopamine D 2 -like receptor involvement in this behaviour.

The Selective 5-HT6 Receptor Antagonist Ro4368554 Restores Memory Performance in Cholinergic and Serotonergic Models of Memory Deficiency in the Rat

“…The present data suggest that it may involve an increase in cholinergic transmission (Riemer et al, 2003;Shirazi-Southall et al, 2002). Previous behavioral studies indicated such an enhanced cholinergic neurotransmission after administration with a 5-HT 6 antagonist (Bentley et al, 1999). The present finding that Ro4368554 reversed a scopolamine-induced deficit in novel object recognition corroborates other studies showing scopolamine reversal in cognition tasks (Foley et al, 2004;Meneses, 2001;Woolley et al, 2003).…”

Effects of Typical and Atypical Antipsychotics and Receptor Selective Compounds on Acetylcholine Efflux in the Hippocampus of the Rat

“…In the absence of binding data, data from other pharmacological and biochemical studies revealing activity at the respective receptors were used to select relevant doses (see e.g. Nomikos et al 1992;Andersson et al 1994Andersson et al , 1995Nomikos et al 1994;Bentley et al 1999;Grottick et al 2000;Marcus et al 2000). For example, based on a number of previously published preclinical data Andersson et al 1995;, it is estimated that full occupancy and blockade of D2 receptors in the brain is achieved by the dose of raclopride used.…”

“…ketanserin, ritanserin, and mesulergine, which exhibit varying degrees of 5-HT 2A vs. 5-HT 2C receptor selectivity (Hirano et al 1995;Consolo et al 1996;Zhelyazkova-Savova et al 1999). Interestingly, both clozapine and olanzapine, in contrast to other antipsychotic drugs tested, appear to show high affinity for the 5-HT 6 receptors (Roth et al 1994;Bymaster et al 1999), and 5-HT 6 receptor antagonists purportedly increase cholinergic function in the brain (Bentley et al 1999). Accordingly, selective action at the 5-HT 6 receptors could account for the pronounced effects of clozapine and olanzapine on hippocampal ACh outflow, as compared with the other antipsychotic drugs.…”

A Null Mutation of the Serotonin 6 Receptor Alters Acute Responses to Ethanol

“…Some studies indicated that 5-HT 6 R antisense oligonucleotides (Bourson et al, 1995;Sleight et al, 1996) or 5-HT 6 R antagonists (Unsworth and Molinoff, 1994;Sleight et al, 1998;Bentley et al, 1999;Routledge et al, 1999) produced yawning-stretching behaviors that could be blocked by the muscarinic cholinergic antagonist atropine or potentiated by the cholinesterase inhibitor physostigmine. Other studies have implicated Rs in the modulation of cognitive processes (Russell and Dias, 2002).…”

“…Thus, the expression pattern and pharmacological properties of Rs indicate that they may contribute to serotonergic modulation of clinically relevant neuropsychological processes and psychopharmacological responses. Administration of 5-HT 6 R antagonists and antisense oligonucleotides have been reported to produce several behavioral effects in rodents, including feeding suppression (Svartengren et al, 2004), yawning and stretching (Bourson et al, 1995;Sleight et al, 1996;Sleight et al, 1998;Bentley et al, 1999), decreased anxiety-related behaviors (Hamon et al, 1999), and improved performance in learning and memory tasks (Meneses, 2001;Rogers and Hagan, 2001;Woolley et al, 2001;Russell and Dias, 2002;Lindner et al, 2003;Riemer et al, 2003).…”