Le bâillement, du réflexe à la pathologie

mise à jour
26 septembre 2002
1990; 40; 174-178
Effects of REM sleep deprivation
on ACTH induced yawning
LL Lobo, BG Neumann, DS Eidman, S Tufik
Department of psychobiology, Universidade de Sao Paulo, rua Botucatu, 862 Andar, SP 04034-062 Sao Paulo Bresil
Abstract : Central administration of ACTH in rats induces yawning and stretching. In order to study the effects of REM sleep deprivation on ACTH-induced yawning, the peptide was injected immediately after the REM sleep deprivation period or 24 h later. REM sleep deprivation impaired ACTH-induced yawning, but after a 24-hour recovery period, rats displayed a number of yawns similar to those in control animals. Implications for an involvement of dopaminergic and mainly cholinergic systems are discussed.

Introduction : Yawning behavior can be induced in rats by systemic administration of very small doses of apomorphine or other dopaminergic agonists and cholinergic agonists, as well as by intracerebral injection of ACTH or some of its analogues. This syndrome, which is also characterized by stretching and penile erection, is suggested to be a behavioral consequence of the involvement of dopaminergic and cholinergic systems.

Although the exact mechanisms that participate in the stretching-yawning syndrome (SYS) have not yet been completely elucidated, it appears that the central cholinergic muscarinic receptors are of fundamental importance. Atropine and scopolamine, both central cholinergie antagonists, block the SYS induced either by dopaminergic and cholinergie agonists or by ACTH and its analogues. Recently, Wood et al. have proposed that the septal-hippocampal cholinergic neurons are necessary to elicit the SYS following ACTH or a-MSH since intraventricular injection of these neuropeptides increases the acetylcholine turnover rate in the hippocampus of rats.

We have recently demonstrated that rats submitted to 96 h of REM sleep deprivation show a great reduction of yawnings induced by apomorphire (direct dopaminergic agonist), physostigmine and pilocarpine (indirect and direct cholinergic agonists, respectively) when they are tested immediately after the end of the deprivation period. However, if the animals are allowed to rest for 24 h after the period of sleep deprivation, the yawning induced by pilocarpine returns to control values, whereas apomorphine- and physostigmine-induced yawning is still reduced [unpublished. data]. This suggests that REM sleep deprivation affects the dopaminergic and cholinergic systems in different ways. Because of,this and since the mechanism through which ACTH induces the SYS is attributed to the activation of muscarinic receptors, the present study intended to verify the effects of REM sleep deprivation upon yawning induced by ACTH, immediately after the end of the deprivation period, and after 24 h of recovery in order to further the understanding of the systems involved in REM sleep deprivation and yawning. [...]

Discussion : With regard to the interaction of dopaminergic-cholinergic neurons and yawning, dopaminergic neurons have been reported to play an inhibitory role in the control of the septal-hippocampal cholinergic neurons. Also, there is an indication that the cholinergic system of the hippocampus participates in the SYS induced by ACTH and a-MSH, since a 2-fold elevation of the hippocampal turnover rate of acetylcholine has been observed after the intraventricular administration of these polypeptides, being suggestive of an involvement of muscarinic acetylcholine receptors. Furthermore, the SYS induced by ACTH is inhibited by atropine and scopolamine, both central cholinergic antagonists, and also by the neuroleptic chlorpromazine. Scopolamine also inhibited yawning induced by apomorphine. Sulpiride, a specific dopamine receptor blocker, antagonizes apomorphine-induced yawning, but fails to affect this behavior induced by ACTH, which suggests that ACTH induces yawning by acting on neuronal pathways different from those of dopamine agonists. It has been described that lesions at the paraventricular nucleus prevent apomorphine-, but not ACTH-induced yawning, leading once again to the relationship between ACTH and acetylcholine during the display of yawning.

It bas been reported that REM sleep deprivation produces dopaminergic supersensitivity, probably inducing a cholinergic subsensitivity, which is also observed after chronic administration of haloperidol. Similarly, REM-sleep-deprived animals show a reduced number of yawns in response to apomorphine, pilocarpine and physostigmine, suggesting a lowered responsiveness of either dopaminergic and/or cholinergic systems. It seems that chronic haloperidol and probably REM sleep deprivation act initially by blocking the dopaminergic system and consequently releasing the cholinergic neurons from the dopaminergic inhibition. Indeed, it has been demonstrated in our laboratory that the recovery does not occur simultaneously in dopaminergic and cholinergic systems (see Introduction).

It is widely accepted that stressful situations provoke a rise in hypothalamo-hypophysial-adrenal axis activity, and recent data suggest that adrenocortical hormones modulate dopaminergic receptor function. It must be considered that REM sleep deprivation is a stressful procedure, and it is conceivable that during this treatment there is an intense production and release of ACTH, leading to a decreased sensitivity to ACTH, and a possible reduction in the number of drug-induced yawns, since this behavior seems to depend on an entire chain of systems (ACTH-acetylcholine-dopamine).

The delayed onset of the yawning, which was observed alternating with pende erection and stretching, is probably due to the slow diffusion of the active material from the site of injection into the sites of action [4], or because ACTH acts through an interaction with muscarinic acetylcholine receptors, standing for the latency to trigger the cholinergic system.

In summary, REM sleep deprivation for 96 h lowers the responsiveness to intracerebroventricular injection of ACTH, as evidenced by yawning behavior. A 24-hour recovery period after REM sleep deprivation restores the system responsible for the displaying of yawning after the central administration of ACTH. Together with the data obtained by Wood et al. and Gower et all suggesting an involvement of the acetylcholine receptor after ACTH treatment, it seems consistent to accept the hypothesis that yawning is a behavior mediated through the activation of cholinergic neurons.

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