mise à jour du
26 janvier 2006
Cholinergic mediated yawning and analgesia in rats: differential effects of muscarinic agonists and antagonists
Gower AJ
Merrell Dow Research Institute, 16 rue d'Ankara, 67084 Strasbourg Cedex, France.


The existance of muscarinic receptor subtypes in the CNS is now well accepted. Support for this comes mainly from binding studies and depends heavily on the selectivity of the muscarinic antagonist, pirenzepine (Hoss & Ellis, 1985). However, it is important to know whether these receptor subtypes have functional correlates. We investigated a) the ability of cholinergic agonists to elicit 2 centrally mediated responses, yawning (Urba-Holmgren et al. 1977) and analgesia (Karczmar & Dun, 1978) and b) the ability of cholinergic antagonists to inhibit these behaviors elicited by physostigmine, 0.1 mg/kg subcutaneously (s.c.).
Experiments were carried out between 9.00-13.30h using male Sprague-Dawley rats (250-320g). Induction of yawning was assessed by counting the number of yawns elicited in a 30 min period immediately following s.c. injection of the agonists. Effects of antagonists were assessed by injecting them 30 min prior to physostigmine and counting the yawns elicited during 30 min after physostigmine. ED50 values for inhibition of yawning were calculated. Analgesia was measured, using an Appelex DS 20 Tail-Flick apparatus, in terms of the tail flick response to a focussed heat stimulus. Effects of agonists were determined 20 min after s.c. injection. Effects of antagonists were determined by injecting them s.c. 30 min before physostigmine and measuring the tail-flick response 20 min after physostigmine. ED50 values for inhibition of analgesia were calculated. In view of poor penetration of pirenzepine into the brain, the effects of pirenzepine and atropine were also determined following injection into the lateral ventricle (i.c.v.).
Yawning was induced by physostigmine (0.025-0.4 mg/kg); RS86 (0.05-2.5 mg/kg) and pilocarpine (0.5-4.0 mg/kg) but not by oxotremorine (0.001-0.3 mg/kg) nor arecoline (0.5-2.0 mg/kg). In contrast all 5 agonists produced analgesia over these dose-ranges. Neostigmine (0.05-0.2 mg/kg), bethanecol (0.1-10 mg/kg) and McN-A-343 (5-20 mg/kg) were inactive or marginally active in both tests. Clear differences were obtained in the potencies of drugs inhibiting yawning (Y) and analgesia (A), (ED50 values in the table); in particular pirenzepine i.c.v. inhibited yawning but not analgesia.
These results show that it is possible to differentiate muscarinic receptors on the basis of behavioural responses. Yawning was pirenzepine-sensitive and oxotremorine-insensitive whereas the opposite was found for analgesia.
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