British Journal of Pharmacology 1999-04-01

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

J C Bentley, A Bourson, F G Boess, K C Fone, C A Marsden, N Petit, A J Sleight

Index: Br. J. Pharmacol. 126 , 1537-1542, (1999)

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Abstract

1. The present study examined the effects of the selective 5-HT6 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). 2. In non-quantified behavioural observations, animals treated with Ro 04-6790 (3, 10 or 30 mg kg(-1), i.p) showed no overt behavioural signs except a dose-dependent reduction in locomotor activity and a behavioural syndrome of stretching, yawning and chewing. The latter behaviour was most pronounced between 30 and 90 min following the administration of Ro 04-6790. 3. Detailed analysis of the stretching and yawning behaviour showed that Ro 04-6790 (3, 10 or 30 mg kg(-1), i.p.) dose-dependently induced stretching. The number of stretches observed following treatment with either Ro 04-6790 (10 mg kg(-1) i.p.) or Ro-04-6790 (30 mg kg(-1), i.p.) was significantly 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 significantly greater than in those treated with saline. 4. Pretreatment (30 min) with the non-selective muscarinic antagonists scopolamine (0.1, 0.3 or 1 mg kg(-1), i.p.) and atropine (0.3, 1 or 3 mg kg(-1), s.c.) but not methylatropine (1, 3 or 10 mg kg(-1), s.c) significantly inhibited stretching induced by Ro 04-6790 (30 mg kg(-1), i.p.). 5. The dopamine D2-like receptor antagonist, haloperidol (0.03, 0.1 or 0.3 mg kg(-1), s.c.) given at the same time as Ro 04-6790 (30 mg kg(-1), i.p.) had no effect on the stretching induced by the 5-HT6 antagonist. 6. These data suggest that systemic injection of the 5-HT6 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-HT6 receptor blockade. There is no evidence for dopamine D2-like receptor involvement in this behaviour.