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

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). 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. 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. 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.). 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. 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. British Journal of Pharmacology (1999) 126, 1537–1542; doi:10.1038/sj.bjp.0702445