mise à jour du
12 décembre 2002
Revue Canadienne Biolologie
Stretching and yawning movements after intracerebral injection of ACTH
GL Gessa, M Pisano, L Vargiu, F Crabai, W Ferrari
Institutes of Pharmacology, University of Cagliari and University of Modena, Italy
Tous les travaux de MR Melis & A Argiolas 
Tous les travaux de M Eguibar & G Holmgren  


Previous studies have demonstrated that the injection of natural or synthetic ACTH and MSH into the cerebrospinal fluid (CSF) of mammals induces a typical syndrome characterized principally by frequently repeated stretching and yawning movements.

This effect, which has been observed in dogs, cats, rabbits, monkeys and rats, begins 30 minutes to two hours after the injection of small quantities (micrograms) of ACTH or MSH into the cisterna magna or into the lateral ventricles, and the effect lasts for many hours. In some species (dogs, cats) stretchings are predominant; in other species (monkeys, rabbits) yawnings prevaill.


The most important results of our previous work are the following: (a) the stretehing syndrome may be induced only by peptides possessing ACTH and/or melanocyte-stimulating (MSH) activities; (b) it can be induced also after adrenalectomy; (c) it can be obtained only by injection of the above substances through the CSF route, (d) the effective doses are very low, in the order of micrograms (0.5 µg/kg for the most active purified hormonal preparations) ; (e) the stretching yawning syndrome can be evoked also in anesthetized animals; (f) this effect can be antagonized by chlorpromazine, atropine, morphine, but is not modified by reserpine, LSD25, gamma-aminobutyric acid and by monoamineoxidase inhibitors.

The experiments reported here were donc to identify the site (S) of action of ACTH in the brain and to study the effect of intracerebrally injected ACTH. [...]

Discussion : Our results appear to localize the sites of action of ACTH in the CNS to two principal areas; the hypothalamus and the caudate nueleus. The fact that the caudate nucleus shows a far greater sensitivity to the action of ACTH than other extra pyramidal regions, (putamen, pallidum, substantia nigra, etc.) suggests the possibility of a diffusion of ACTH from the caudate nucleus to the hypothalamus by way of the CSF. Of the hypothalamic structures, those closer to the hypophysis appeared to be the most sensitive to the action of ACTH. Our results indicate that the delay in the onset of the symptomatology following the intracisternal injection of ACTH is due in part to the time required for the active material to reach its site of action and, in part, to some other mechanism, since the latent period could not be reduced under 7 minutes. The fact that the stretching yawning syndrome is often accompanied by sexual excitement suggests that receptors responsible for this effect are connected to or near centers controlling sexual activity.

Our findings add further support to the concept that ACTH and MSH play a physiological role on the CNS of mammals. In fact, ACTH and MSH induce an exaggeration of a physiologieal function, namely the stretching. The active doses are very small, and the site of action is the hypothalamus where ACTH and MSH have been demonstrated to be present as well as in the hypophysis.

At present, we do not know whether the behavioral and EEG arousals are dependent upon the propioceptive imputs secondary to the stretching movements. However, we are inclined to think that the two effects are intimately connected. In fact, stretching and yawning are two physiological acts that might be considered as an effort of the body to delay the onset of sleep and as a mechanism to reinforee wakefulness after sleep: stretchiii," and yawning are arousal mechanisms.

As a working hypothesis we suggest that hypothalamic areas sensitive to ACTH are connected with the brainstem descending and ascending reticular formation, which in turn are responsible for stretching and arousal effect. This hypothesis is supported by the fact that the stretching effect is suppressed by drugs known to block the reticular formation.

ABRÉGÉ - L'injection d'ACTH dans le liquide céphalorachidien ou directement dans le cerveau a pour effet d'induire un syndrome caractérisé par des étirements et des bâillements répétés fréquemment. L'ACTH synthétique a été injectée dans différentes aires du liquide céphalorachidien et du cerveau à travers des canules laissées à demeure. Les résultats de ces expériences ont démontré que les aires entourant le troisième ventricule sont les plus sensibles à l'action neurotrope de l'ACTH. Chaque mouvement d'étirement est accompagné d'un réveil "behavioral" et EEG. L'injection d'ACTH dans ces aires produit aussi une excitation sexuelle.

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