i860 



1IVNDBOOK OF PHYSIOLOGY 



\1 IKOPHYSIOI.OGY III 



been achieved the brain appears to be little affected, 

 if at all, by the level of circulating thyroid hormone. 

 Preliminary observations indicate that this lack of 

 effect is not the result of the inability of thyroxine to 

 pass the blood-brain barrier (unpublished observa- 

 tions). It may, perhaps, reflect more a role for 

 thyroxine in the metabolism of the brain when the 

 synthesis of proteins and oilier structural and enzy- 

 matic components utilize a prominent portion of the 

 total energy consumption, as during growth and 

 maturation, but little influence of the hormone 

 when development is complete and the energy now 

 derived almosi exclusively from the metabolism of 

 carbohydrates is utilized chiefly for the support of 

 cerebral functional activity (179). 



steroid hormones at that time (61, 62). On the other 

 hand, in postpubertal human males, castration has 

 been reported to cause a fall in cerebral oxygen 

 consumption, and the postoperative administration 

 of the steroids, desoxycorticosterone glucoside or 

 testosterone, cause, if anything, a rise in the cerebral 

 metabolic rate back toward the precastration level 

 ((Si ). As for other adrenocortical hormones, Bergen 

 and co-workers (11) have observed in adrenalecto- 

 mized animals a fall in cerebral metabolic rate which 

 was restored to normal by adrenocortical extract and 

 cortisone but not by desoxycorticosterone. In man 

 neither adrenocorticotrophic hormone (3, 160, 167) 

 nor cortisone (1671 have been found to have an) 

 significant effect on cerebral metabolic rate. 



PITUITARY, ADRENAL CORTICAL AND SEX HORMONES. 



The relatively few reported studies, particularly in 

 man, on the effects of the pituitary, adrenal cortical 

 and sex hormones on the metabolism of the central 

 nervous system in vivo, with a few exceptions, indicate 

 vctv little effect of these hormones, at least in the 

 mature individual. In human adult patients with 

 preadolescent hypopituitarism, who on an endocrine 

 basis had not developed through puberty, Gordan 

 (61) found significantly elevated values for cerebral 

 oxygen consumption similar to those observed by him 

 in preadolescent testicular eunuchoidism (61). Since 

 the former group is characterized by low and the 

 latter group by high circulating pituitary gonado- 

 tropin, it cannot be this hormone which is involved 

 in the altered cerebral metabolic rate. In castrated 

 prepubertal rats there is similarly an elevated cerebral 

 oxygen consumption (29, 33, 61), and this is restored 

 to normal by the administration in vivo of any one of a 

 number of steroids, testosterone, methv ltestosterone, 

 epitestosterone, progesterone, anhydrohydroxypro- 

 gesterone, desoxycorticosterone acetate and cortico- 

 tropin, but not by estradiol- 1 7/8 (54, 61). An 

 additional steroid, 2 l-hydrox) pregnane-3 ,20-dione, 

 has recently been found to produce in endocrinologi- 

 cal!) normal man, not onlv a profound reduction in 

 cerebral oxygen consumption but anesthesia as well 

 (6l, 64). Gordan (61) suggests, therefore, that the 

 androgenic and adrenal cortical steroids normally 

 maim. mi a 'braking' action on the cerebral metabolic 

 it< .mil when 'bin ient, as In preadolescent testicular 

 eunuchoidism or preadolescent hypopituitarism, 

 there is a release and elevation of the cerebral meta- 

 bolic 1.1I' lie further postulates that the sleep fill 

 in human cerebral metabolic rate at piiberlv (87) 



is the result of tin- increased production oi these 



ADRENAL MEDULLARY HORMONES. The first chemical 



agent to be found to accelerate the cerebral metabolic 

 rate in normal man is the adrenal medullary sym- 

 pathomimetic amine, /-epinephrine. When admin- 

 istered by continuous intravenous infusion in suffi- 

 cient amounts to raise the arterial pressure, it was 

 found to produce consistent and significant increases 

 in the rate of cerebral oxygen consumption (104). 

 Because of the relationship of this substance to the 

 phenomenon of 'anxiety,' it has been suggested that 

 it is the mediator of the stimulation of cerebral 

 metabolic rate in that emotional state (l 73)- Sensen- 

 bach and his associates (i(S6l have failed to find anv 

 effect of /-epinephrine on human cerebral metabolic 

 rate, but they administered the drug iniramuscul.it lv 

 in (k)ses insufficient to alter the arterial blood pressure. 

 Recently, mephentermine, a synthetic amine closely 

 related to epinephrine, has been found also to raise 

 the cerebral metabolic rate when administered 

 intravenously in pressor doses (140). The other 

 adrenal medullary amine, /-norepinephrine, does not 

 appear to have anv obvious effect on cerebral metabo- 

 lism (104, 166). 



Psychotomimetic and Tranquilizing Drugs 



Considerable interest has recenllv been focused mi 

 two classes of drugs which appear to be capable "I 

 producing profound alterations in psychological 

 functions. One class, the psychosomimetic drugs, is 

 reputed to produce mental symptoms which simulate 

 those of the sponianeousK occurring psychoses such 

 as schizophrenia (14"), 181 I. The other class, the 

 tranquilizing or ataractic drugs, has been employed 

 Clinically for the alleviation or amelioration of many 



