FREE AMINO ACIDS IN BRAIN 467 
this type of study on GABA, glutamic acid and glutamine, the other amino acids 
should not be overlooked. 
All of the values obtained in the present study, including the alterations to be 
noted in some of the substances, come within the “normal "range that may be 
constructed by collecting all the data for normal rat brain to be found in the liter- 
ature*. Thus, actual concentrations of substances can be compared only within a 
given experimental series of the same strain. Furthermore, the response to a chal- 
lenge also may vary from strain to strain. For example, with the Wistar rats reported 
here, hydroxylamine produced an increase in GABA concentration of 38°%**. The 
same dose of hydroxylamine in Sprague-Dawley rats resulted in a rise of only 9%. 
In preliminary experiments with Royal Hart animals, it was found that the normal 
concentration of GABA and the response to hydroxylamine varied too much to 
show any consistent trend. 
The changes that were observed in the concentration of some of the amino acids 
are as follows. In the hydroxylamine-treated animals, there is the expected increase 
in the concentration of GABA, though the effect is not as pronounced as has been 
found by BAXTER AND RosBeErTS®: ® in Sprague-Dawley and Wistar rats. Large 
increases in GABA after hydroxylamine were also obtained by EIDELBERG et al. in 
cats’ and monkeys’. Reserpine had no effect on GABA; BALZER, HOLTZ AND PALM®: 1°, 
on the other hand, have found a clear-cut decrease in mice. 
A small, but definite decrease in GABA occurred after administration of imi- 
pramine, desmethyl-imipramine and chlorpromazine. (In the hands of OKUMURA 
et al.2, chlorpromazine caused a slight increase.) The decrease in brain GABA con- 
centrations associated with convulsions is a well-known phenomenon; it occurs 
after initiation of seizures by various agents: hydrazides®: *, 1, 2, KCN (ref. 13), and 
pyridoxine antagonists®, 4-16, Hydroxylamine, in complementary fashion, has anti- 
convulsant properties and raises the brain GABA concentration’: §. However, it is 
by now quite certain that the decrease in GABA is itself not the “cause” of the 
seizures, but, rather, that the fall in GABA is, as PurpuRA ef al.° have stated, 
but one manifestation of the complex of metabolic changes initiated by the con- 
vulsive agent (cf. also refs. 9, 12, 16). There are many observations that support 
this view: some convulsive agents or procedures have no effect on GABA concen- 
trations®: 9, 41, 16, 17; |-2 4-diaminobutyric acid causes seizures and raises the GABA 
concentration!?: 18; pyridoxine prevents the convulsions produced by some hydra- 
zides without preventing the decrease in GABA (ref. 9); thiosemicarbazide, given 
in conjunction with hydroxylamine, causes convulsions even though the GABA 
concentration is elevated®; applied topically, methoxypyridoxine causes a much 
smaller decrease in GABA than when administered intravenously, though the 
convulsive effect is as pronounced”; the seizure susceptibility of areas of the normal 
cortex is not related to the concentration of naturally occurring GABA (refs. 19, 20). 
The decreases in GABA noted in the present work provide some further evidence 
that a fallin GABA is not directly related to the convulsive state ; the chlorpromazine- 
treated animals were sedated, and the imipramine- and desmethyl-imipramine- 
treated animals showed no marked changes in behavior. 
* See the following paper. 
** With NH,OH:HCI at a dosage of 71 mg/kg, the increase in GABA concentration in the 
Wistar rats was 57%. 
References p. 469/470 
