mise à jour du
10 juin 2004
Behavioural Brain Research
Adrenalectomy and dexamethasone
replacement on yawning behavior
J Anias-Calderon, L Verdugo-Diaz, R Drucker-Colin
Depto. de Neurociencias, Instituto de Fisioloġa Celular, Mexico


Introduction Yawning is a phylogenetic behavior observed in mammals, birds, and possibly reptiles. Although it has
been studied from Hypocrates, the first experimental report was published in 1963 by Ferrari et al.
The physiological function of yawning behavior is still unknown. Ferrari's studies showed that adrenocorticotropine hormone (ACTH), a-melanocyte-stimulating hormone (a-MSH) and related peptides induce the stretching-yawning syndrome, when injected directly into the cerebral ventricles or third ventricle, but not by peripheral injection. Since then, several reports have attempted to elucidate the mechanism of yawning behavior.
Thus, other hormones like oxytocin and testosterone, neurotransmitters such as dopamine and nitric oxide, ions and brain structureshave been described as being involved in this behavior. In addition, some researches have shown
that the hypothalamicÐadrenal axis (HPA) may also be involved. The hypothalamus has been identified as one ofthe brain sites for the action of ACTH and a-MSH's on stretching-yawning syndrome. Stress effects on yawning behavior has also been studied. Stressful manipulations modify yawning's induction by drugs and yawning trace adjustment to unfamiliar environments in the laboratory. To date, there is only one study showing an effect of dexamethasone on yawning behavior, but there are no studies on the role of adrenal glands. The aim of the present study was, therefore, to investigate the effects of adrenalectomy (ADX) and dexamethasone (DEX) replacement on yawning behavior. [...]
Discussion Our results show for the first time that ADX practically abolished spontaneous and APO-induced yawning. This effect although reverted by DEX, was shown not only to be variable in time, but was also dose dependent. The yawning suppression produced by ADX in our study could be understood from two different, but closely related points of view: first, the fall of blood corticosterone levels that is well known to occur following ADX. ADX can change function, structure, or the receptor levels of glucocorticoids which alter normal functioning.
The paraventricular nucleus could change their activity by glucocorticoid reduction. This nucleus is also an important structure involved in yawning behavior. The reduction of corticosterone levels as a main cause for yawning suppression is supported by the fact that DEX replacement restored yawning behavior. ADX produces a vertical downward shift of amphetamine and cocaine locomotor responses, which is reversed in a dose-dependent manner by corticosterone administration.
Further evidence comes from the fact that adrenalectomy reduces the locomotor response induced by injection of psychostimulant drugs into the nucleus accumbens, which is then re-established by restoring basal levels of corticosterone. In addition, adrenalectomy decreases extracellular concentration of dopamine in the nucleus accumbens, both in basal conditions and in response to psychostimulant drugs and these effects are reverted by corticosterone replacement. Moreover, dopamine administration into the nucleus accumbens elicits yawning behavior. Debora et al. showed that single or repeated dexamethasone does not modify apomorphine-induced yawning.
The discrepancy of these results with that shown in the present study could be explained by the dose used. We observed similar results at the lower concentration used (1 mg/kg). The relation of ADX effects through changes of PVN nucleus activity is supported by the fact that PVN lesions prevents yawning induced by oxytocin and APO, but not by ACTH administered intracerebrally. It is thus conceivable that a PVN functional change provoked by ADX is strongly involved in the suppression of spontaneous and APO-induced yawning. The different effects observed after a single injection of DEX through 28 h in sham animals, could be produced by the different stressors elicited, which induce different responses on yawning frequency. Some reports showing that 24 h REM sleep deprivation suppresses ACTH-induced yawning, whereas 96 h of REM deprivation abolished APO and cholinergic agonist-induced yawning, effects lasting even afterafter a 24-h recovery period.
Furthermore, weak and intermittent stress, such as foot shock and forced swimming, provokes increased yawning with similar drugs. Such controversial results are in agreement with some reports which have shown that the increase of ACTH and corticosterone in plasma are different depending on the nature of the stress. Thus, we could propose that the suppressive effects on YF observed in our study immediately after injection, of a supraphysiological dose of DEX could be compared to the effect of strong and constant stress, while the increase of YF occurring at 3 h (5 mg/kg), 5 h (10 mg/kg), and 24 h (20 mg/kg) could be caused by the vanishing effects of DEX and similar to the effects of weak and/or intermittent stress. The effect of 1 mg/kg of DEX falls within this latter category. The latter is supported by the fact that one low dose of DEX (0.25 mg/kg) increases pilocarpine-induced yawning.
The yawning induced by ACTH-MSH peptides and dopamine receptor agonists is abolished by hypophysectomy but not by neonatal monosodium glutamate treatment, which depletes brain opiomelanocortin peptides. As a result of these findings, it has been suggested that peripheral and central ACTH-MSH peptides are not involved in the yawning response to dopamine receptor agonist. On the other hand, our results show that adrenalectomy has effects similar to hypophysectomy on YF, therefore, it can be inferred that adrenal glands have an important role in this behavior. There is no doubt that the removal of the adrenal glands probably alters several factors which may have an impact on yawning, and therefore more studies are needed to fully understand this complex behavior. Nonetheless, our study points to the important role of the adrenal glands and glucocorticoids in the control of yawning.