110 MARTIN G. LARRABEE AND PAUL HOROWICZ 



'membrane' around the cell, but to other membranes as well, e.g., mitochondrial 

 membrane and nuclear membrane). 



The relationship between these two sets of mechanisms is brought out clearly, 

 if, for example, one considers that the initiation and conduction of nerve im- 

 pulses are manifestations of electrochemical processes localized in the surface 

 structure of nerve cells and their axons. Action currents develop subsequent to 

 changes in structural orientation at the surface. Brink has pointed out that 

 such processes are "self-limiting and cyclic, being completed by cellular proc- 

 esses that restore the original excitable state." The molecular arrangements 

 in the resting cell that are "capable of such a transition from one state to 

 another" have been referred to as a metastable structure (Brink) in contrast 

 to the excitable structure. The metastable structure responds to certain stimuli 

 and controls ionic fluxes which give rise to potential changes. The stability of 

 the membrane would depend on the molecular organization of this structure, 

 and consequently, one would suppose that the initial, fundamental effects of 

 alcohols could be at this locus. 



Alcohols in the proper concentrations can be considered as narcotics or 

 anesthetics. Evidence exists (Arvanitake; Graham; Hensel and Zotterman) 

 that narcotics in concentrations lower than that necessary to induce narcosis 

 act to produce stimulation of neural structures. Mullins has suggested that if a 

 chemical agent lowers the threshold to the point of self excitation before causing 

 narcosis, similar self excitation of olfactory receptors can occur when a certain 

 mole fraction of chemical agent has been reached in their membranes. On the 

 basis of a recent series of experiments we wish to suggest that ethyl alcohol 

 acts in this way to produce stimulation in low concentration and depression in 

 high concentration. 



Using the local perfusion technique, ethyl alcohol in concentrations from 5 

 mM. up to 800 raM. was perfused through a pial vessel directly into a localized 

 area of the cerebral cortex of the cat. Evoked responses were obtained from 

 the dendrites and cell bodies in the perfused area by direct electrical stimula- 

 tion (bipolar stimulating electrodes connected to a Grass stimulator). Experi- 

 ments thus far indicate that stimulation is obtained with concentrations 

 between 5 and 25 mM. Concentrations of 50 mM. and above induce depression. 

 During the perfusion of 5 mM. ethanol stimulation — i.e., increase in amplitude, 

 for example, of the dendritic response has been seen, of as much as 65%. Thus 

 far some variation in the degree of stimulation or depression by a particular 

 concentration has been observed from animal to animal. It is quite probable 

 that this is real — and not error — and related to other factors which have affected 

 the state of the membranes and thus of the excitability of these cells at the 

 particular time during which the perfusion took place. 



It must be noted that depression of the response can be induced by concen- 

 trations far below those which significantly inhibit the rate of oxygen consump- 



