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.
Gessa GL
Stretchings and yawnings induced by
adrenocorticotrophic hormone Nature 23/07/1966;
5047; 426-427
Gessa GL
Stretching and yawning movements after
intracerebral injection of ACTH Revue Canadienne
Bioliologie; 1967, 26, 3, 229-236
Kimura H,
Yamada K, Nagashima M, Matsumoto S, Ishii Y,
Yoshida S, Fujii K, Furukawa T Role of
adrenergic neuronal activity in the yawning
induced by tacrine and NIK-247 in rats.
Pharmacol Biochem Behav 1992; 43; 4; 985-91
Kimura
H, Yamada K, Nagashima M, Furukawa T
Involvement of catecholamine receptor activities
in modulating the incidence of yawning in
rats.Pharmacol Biochem Behav 1996; 53; 4;
1017-21
Laing J, Ogilvie R
EEG correlats of yawning during sleep onset
Sleep Research 1988; 17; 98
Molgilnicka
E REM sleep deprivation changes behavioral
response to catecholaminergic and serotoninergic
receptor activation in rats Pharmacol Biochem
Behav 1981; 15; 1; 149-151
Serra
G , Collu M and Gessa GL Yawning is elicited
by D2 dopamine agonists but is blocked by D1
antagonist Psychopharmacology 1987; 91;
330-337
Serra G,
Gessa GL Hypophysectomy prevents yawning and
penile erection but not hypomotility induced by
apomorphine Pharmacology Biochemistry &
Behavior 1983; 19; 917-919
Serra
G et al Cycloheximide prevents apomporphine
induced yawning, penile erection and genital
grooming in rats European Journal of
Pharmacology 1983; 86; 279-282
Stahle
L Do autoreceptors mediate dopamine
agonist-induced yawning and suppression of
exploration ? a critical review.
Psychopharmacology 1992; 106; 1-13
Neumann BG,
Troncone LR, Braz S, Tufik S Modifications
on dopaminergic and cholinergic systems induced
by the water tank technique: analysis through
yawning behavior Arch Int Pharmacodyn Ther 1990;
308; 32-8
Stahle
L Do autoreceptors mediate dopamine
agonist-induced yawning and suppression of
exploration ? a critical review.
Psychopharmacology 1992; 106; 1-13
Tufik S
Does REM sleep deprivation induce subsensitivity
of presynaptic dopamine or postsynaptic
acetylcholine receptors in the rat brain?
European Journal of Pharrnacology 1987; 140;
215-219
Tufik S
Effects of stress on drug induced yawning
Physiology & behavior 1995; 8; 1;
1881-18
