46 METABOLISM IN CHANGED CEREBRAL ACTIVITY 



having a stabilizing effect. In large animals such as the cat or dog 

 (cf. Klein and Olsen, 1947) administration of barbiturates appeared 

 to have no demonstrable effect upon the quantities of phospho- 

 creatine in the brain. In the preparation of such animals, however, 

 either a local anaesthetic or general ether anaesthesia was used and 

 any additional effects of a barbiturate may not have been detected 

 by changes in levels of phosphocreatine. 



The effect of a barbiturate in increasing or stabilizing the 

 quantity of a rapidly metabolized phosphate such as phospho- 

 creatine is suggestive of an action resulting in a decreased rate of 

 utilization. In vivo this problem has been approached by studying 

 the rates of phosphorus exchange in both the acid-soluble phos- 

 phates and the phospholipids. Ansell and Dohman (1957) observed 

 that anaesthesia, induced by thiopentone, had no effect upon the 

 specific radioactivity of the total acid-soluble phosphates of the rat 

 brain. They pointed out, however, that since the specific radio- 

 activities of inorganic phosphate and energy-rich phosphates were 

 not measured such data gave no indication of the effects of anaes- 

 thesia upon the formation of these phosphates. Such information 

 is provided by some interesting experiments of Bain (1957) 

 working with the mouse. It was found that after intracisternal 

 injection of radioactive phosphate, the specific radioactivity of 

 adenosine triphosphate was markedly greater in the brains of mice 

 anaesthetized with thiopental or amytal than that found in un- 

 anaesthetized mice. These results would appear to suggest that 

 barbiturates are without adverse effect upon the synthesis of 

 adenosine triphosphate in vivo. On the other hand, Vladimirov 

 and Rubel (1957) noted that amytal anaesthesia apparently 

 decreased the rate of incorporation of phosphate into cerebral 

 hexose monophosphates. This finding is not incompatible with 

 that of Bain (1957) for the relative specific radioactivities of the 

 hexose monophosphate were calculated as the ratio, specific 

 radioactivity of hexose monophosphate/specific radioactivity of 

 adenosine triphosphate. Increase in the specific radioactivity of 

 adenosine triphosphate could therefore lead to a decrease in the 

 relative specific activity of the hexose monophosphate. 



Barbiturate anaesthesia also alters the rate of phosphorus ex- 

 change in the phospholipids. Thus, Dawson and Richter (1950«) 

 found that the incorporation of radioactive phosphate into the total 

 phospholipids of rat brain was significantly reduced by light pento- 



