296 BRAIN MECHANISMS AND LEARNING 



conditioned rcHcx, free from intersignal reactions, was established after 300 

 associations. This was followed by the establishment of the neurosis. 

 Simultaneously with the positive bell sound, on three subsequent occasions, 

 a strong painful electric shock was administered to a hind-leg of the 

 animal and it was observed how many days after the break the normal 

 conditioned reflex would reappear. When the conditioned reflex had been 

 fully re-established, the corticoid composition of the blood in the adrenal 

 vein was examined. 



Although the break of the conditioned reflex was brought about under 

 identical conditions, the figure shows considerable variations in the 

 duration of the inhibitory period. A long inhibitory period showed a close 

 relationship to the adrenal secretion, or rather to the ratio of hydrocorti- 

 sone and corticosterone. In the case of short periods of inhibition the 

 hydrocortisone-corticosterone ratio was low, in prolonged inhibition, 

 however, a high ratio was observed. 



The question of whether or not adrenocortical secretion and duration of 

 inhibition can be brought into a direct causal relationship was answered by 

 our next experiment. In those animals which, prior to the break in the 

 temporary connection had been treated with hydrocortisone for a week, 

 not only was the inhibitory period several times longer than that observed 

 in the animals many months before this treatment, but it was also accom- 

 panied by marked neurotic signs which were not observed in the un- 

 treated animals. 



Those experiments would seem to indicate that the neurotic status 

 caused by the break in the conditioned reflex is influenced by the ratio of 

 the two main components secreted by the adrenal cortex, i.e. hydrocorti- 

 sone and corticosterone. The qualitative difference in the effect of thes-e 

 two compounds on the nervous system has already been pointed out by 

 Woodbury and his co-workers (1949-54). According to their observations 

 hydrocortisone lowers considerably, while corticosterone does not 

 influence, the convulsant threshold of the central nervous system; more- 

 over, corticosterone counteracts the effect of hydrocortisone in this respect. 

 The ratio of the two compounds varies with the individual, and this, 

 according to our investigations, is of importance in the development of 

 the neurotic state. Our experiments on the rat resulted in the same find- 

 ings, on the basis of which the strain examined by us could be divided into 

 four groups with different inhibitory periods. In each group the adreno- 

 cortical activity was found uniform and, what is more, could also be well 

 distinguished quantitatively (Endroczi, Lissak, Telegdy, 1957). 



On the basis of those experiments the effect of the adrenocortical 



