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The γ‐Aminobutyrate Content of Nerve Endings (Synaptosomes) in Mice After the Intramuscular Injection of γ‐Aminobutyrate‐Elevating Agents: A Possible Role in Anticonvulsant Activity
Author(s) -
Wood J. D.,
Russell M. P.,
Kurylo E.
Publication year - 1980
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1980.tb12497.x
Subject(s) - aminooxyacetic acid , glutamate decarboxylase , convulsant , anticonvulsant , chemistry , gamma aminobutyric acid , pharmacology , synaptosome , gabaergic , convulsion , medicine , endocrinology , biochemistry , epilepsy , neuroscience , biology , enzyme , receptor , in vitro
The intramuscular administration of L‐cycloserine, gabaculine, and aminooxyacetic acid caused significant, time‐dependent increases in the γ‐aminobutyric acid (GABA) content of both whole brain and synaptosomalenriched preparations obtained from the tissue, a linear relationship being observed between the two parameters. In contrast, the administration of hydrazine resulted in a large increase in whole brain GABA level, with little change in the synaptosomal GABA content. The key factor in these different responses appeared to be the degree of inhibition of glutamic acid decarboxylase by the drugs. Pretreatment of mice with the GABA‐elevating agents resulted in a delay in the onset of seizures, which was related directly to the increase in synaptosomal GABA content. Although the seizures were delayed, they occurred while the GABA content of nerve endings (synaptosomes) was above that in preparations from untreated animals. The decrease in GABA content at the onset of seizures, expressed as a percentage of the level at the time of injection of the convulsant agent, was, however, reasonably constant. A hypothesis to explain these results is proposed.