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GABA and Epilepsy: Their Complex Relationship and the Evolution of Our UnderstandingDivision of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, University of Southern California School of Medicine, Los Angeles, CA
Because of its abundance in the brain, its ability to produce hyperpolarizing inhibition of almost all neurons, its association with benzodiazepines, and the discovery that many convulsants inhibited its synthesis,
However, the GABA-deficiency theory of epilepsy is less convincing today. GABA agonists were found to intensify seizures in some rodent and human cases. Absence and other generalized seizures in humans often worsened when treated with GABA transaminase inhibitors such as Studies with GABA uptake blockers and the GABAB agonist baclofen are presented in which their combined administration provoked seizures in rats. Baclofen was shown also to increase the incidence of seizures evoked by pentylenetetrazole without increasing seizures due to local injections of excitatory amino acids. Baclofen antagonized the myoclonic effect of 5-hydroxytryptophan in rats with serotonin lesions. Baclofen augments some seizures and inhibits others. Selective inhibition of a particular tract, whether GABAergic or not, may have convulsant or anticonvulsant effects, depending on its connections and the state of the organism. GABA A receptor stimulation is usually but not always anticonvulsant. GABA B receptor stimulation may facilitate absence seizures and related primary generalized seizures. GABAB receptors may be abnormal in some forms of nonfocal epilepsy seen in childhood. It is likely that mutations of GABA transporter and GABAA receptor genes will be found in humans but they will probably not be patients with "pure epilepsy." (J Child Neurol 1992;7:77-86).
Journal of Child Neurology, Vol. 7, No. 1,
77-86 (1992) This article has been cited by other articles:
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-aminobutyric acid (GABA) has often appeared to be the key to epilepsy. Many assumed that "primary" or "genetic" epilepsy must be a disorder of GABA synapses and that GABA agonists would be universal anticonvulsants if permeability and drug metabolism were controlled. The GABA synthetic gene was a logical "candidate gene" for epilepsy. 
