mise à jour du
26 février 2006
Behavioural changes in animals after intracisternal injection with adrenocorticotrophic hormone and melanocytestimulating hormone
Ferrari W
University of Cagliari, Italy
Tous les travaux de MR Melis & A Argiolas 
Tous les travaux de M Eguibar & G Holmgren


A few pharmacodynamic effects of adrenocorticophic hormone do not stem from its adrenocortiotropic properties The crisis of muscular hypertonus (acts of stretching) observed in dogs, cats, rabbits and rats injected intracisternally with small doses of this hormone are probably another example of pharmacological effects independent of its adrenorticotropic properties. Although the behavioural changes following the intracisternal injection of many other hormonal preparations were investigated, the modification of muscular tonus mentioned above is obtained only with small doses of adrenocorticophic hormone or melanocyte-stimulating hormone. The term intracisternal injection indicates the replacement of liquor drawn from the cisterna magna with saline in which the various drugs under investigation are dissolved. The volume of these injections never exceeded 2 ml. in dogs, 1 ml, in cats and rabbits and 0,1 ml, in rats. The pH of the injected solutions was made as close as possible to physiological values.
From Table 1 it can be seen that in the dog these two hormones were the only ones to induce the peculiar crisis of increasing muscular tonus spreading to many different muscular groups and resulting in generalized act of stretching. In the dog the stretching crisis, illustrated in Fig. 1, appears within 1-2 hr. after the intracisternal injections as a recurrent series with intermissions of complete recovery and normal muscular tonus. 4-5 hr after the injection not only does the crisis persist but the time between subsequent stretching acts becomes shorter and shorter so that the onset of one overlaps the end of the preceding one. This lasts for 24 hr and more, ending with complete recovery. This phenomenon appears strictly dependent on the method of administration, for the infusion of comparatively large amounts of melanocytestimulating hormone (1 mgm./kgm.) into the common carotid artery is ineffective.
Stretching crises may also be seen in cats, rabbits and rats under the same conditions. However, a few characteristics may help in differentiating the symptoms caused by the two hormones in different animal species. When melanocyte-stimulating hormone is injected into the cisterna magna of rabbits a short period of convulsions precedes a state of catatonic like stupor. Within 1 hr the latter is interrupted by a stretching crisis often accompanied by yawning. A complete recovery occurs within 4-5 hr. Catatonic like stupor occurs in rats, together with scratching movements of unusually long duration. In cats the stretching crisis follows a period of either drowsiness or catatonic-like stupor. Other symptoms may be associated with the intracisternal injection of these two hormones. It is important to mention that neither rectal temperature (in rabbits) nor bloodreducing substances (in dogs) vary. In dogs eosinopaenia and ptyalism and in rabbits a slight arterial hypotension may occur.
The liquor drawn while the behavioural changes are in progress does not cause either the isolated guinea pig ileum or the isolated rat uterus to contract. Nevertheless the same liquor if injected intracisternally to another dog evokes the symptoms described above. In the latter case the latent period is not shortened as one would expect. The latent period lasts longer after injecting either hormone into the lumbar subaracnoidal space of dogs, but the symptoms remain unchanged.
Since in dogs adrenalectomy does not curtail the muscular hypertonus caused by intracisternally injected adrenocorticotrophic hormone, this effect cannot be due to its adrenocorticotropic activities. Moreover in dogs the intracisternal injection of a number of drugs causing eosinopaenia (histamine, 0.1; 48/80, 1; serotonin creatine sulphate, 0.1; 1-epinephrine, 0.02; 1-ephedrine, 2; d-amphetamine, 1; mgm./kgm.) is not followed by behavioural changes similar to those described above. Finally, chlorpromazine and reserpine injected into the cisterna magna of dogs do not evoke a stretching crisis.
The possible explanations of the mechanism of this pharmacological activity of adrenocorticotrophic hormone and melanocyte-stimulating hormone lack experimental support. Nevertheless as a working hypothesis I suggest that the polypeptide chain common to both hormones is either directly or indirectly involved.