mise à jour 7 mars 2002
1993; 27; 1; 17-20
Effect of scopolamine on spontaneous yawning in men
Skorzewska A, Tesfaye Y , Krishnan B, Schwartz G, Thavundayil J, Lal
Douglas Hospital Research Center, Verdun Quebec
The neuropharmacology of yawning Argiolas A, Melis MR


Introduction : The neurotransmitter regulation of yawning in humans is not well understood. However, there is evidence that cholinergic mechanisms play a role in yawning in animals. In the rat, scopolamine or other centrally active antimuscarinic agents inhibit yawning induced by cholinomimetics, dopamine receptor agonists, as well as various peptides. In.contrast to druginduced yawning, the effect of anticholinergics on spontaneous yawning (i.e. nondrug-induced) in either-animals or humans has rebeived little or no attention. Recently, we have shown that during clinical studies of yawning, placebo induces a yawning response in normal volunteers. This suggested to us the use of placebo as a simple approach to the investigation of spontaneous yawning in man. In the present study we have investigated the effect of Scopolamine on spontaneous yawning in normal subjects.
[...] Discussion : Physostigmine, an anticholinesterase, and pilocarpine, a muscarinic cholinergic agonist, both induce yawning in the rat whereas nicotine is ineffective. Scopolamine (or other centrally active antimuscarinic agents)

inhibits yawning induced by physostigmine or pilocarpine, yawning induced by dopamine receptor agonists, apomorphine and piribedil, as well as yawning induced by alpha-MSH, ACTH 1 -24 and oxytocin. Methylscopolamine, methylatropine, pirenzepine (purely peripherally acting antimuscarinic agents) or mecamylamine (a nicotinic receptor blocker) fail to block yawning induced by cholinomimetics or apomorphine. Further, yawning induced by alpha-MSH or ACTH is associated with an increase in acetylcholine turnover. These data point to activation of central muscarinic cholinergic receptors subserving drug-induced yawning in animals. Whether cholinergic mechanisms are also involved in spontaneous yawning is unknown. Unfortunately, the low frequency of yawning following saline placebo in the rat makes study of this phenomenon in this species difficult; research in the highly spontaneous yawning chacma baboon is impractical. Some data suggest that endogenous dopamine may play a role in spontaneous yawning in animal. The development of a selectively bred line of Sprague-Dawley rats with high yawning frequency may lead to clarification of this problem.

The neurotransmitter mechanism subserving nondruginduced yawniing in man is unknown but some evidence points to the involvement of doparninergic-mechanisms. Evaluation of cholinergic mechanisms in yawning in humans bas not previously been reported. Our observations suggest that nondrug-induced yawning (ie.spontaheous yawning) is not mediated by a central muscarinic cholinergic link. The failure of scopolamine to antagonize spontaneous yawning may reflect an inadequate dose or ïnsufficient time interval between drug administration and termination of monitoring of yawning. However, the dose and time interval were based on clinical use of scopolamine as a single subcutaneous injection to ensure central anticholinergic effects. The significantly greater sleepiness after scopolamine compared with scopolamine placebo suggests that the dose was indeed sufficient to induce a CNS effect.

Environmental triggers that may have contributed to yawning under under experimental conditions include suggestion, boredom, anxiety, lack of social, physical and cognitive stimulation or a decrease in alertness. Drowsiness is believed to induce yawning: whereas during sleep yawning does not occur. In animal studies the effect of drowsiness on yawning bas been ignored in the interpretation of data. Provine et al. found that spontaneous yawning occurs most often after waking and before sleep. He suggested that yawning is a paralingual signal for drowsiness which may be a maneuver to increase alertness. Recent electroencephalographic findings provide some support for this alerting effect. Contrary to the belief that somnolence affects yawning, we found no relation between subjective sleepiness, and yawning under our experimental conditions following eiher placebo or scopolamine. It is possible, of course, that a threshold level of drowsiness maintained over a minimal period of time is required and that these conditions were not. met in our study. Alternately, we may Pe witnessing a masking gffect.

It is possible that the significantly increased drowsiness observed after scopolamine which would normally be accompanied by an increase in yawning was counteracted by anticholinergic effect of scopolamine resulting in the appeareance that there was no effect on yawning.