Kainic Acid Induced Seizures and the GABA System in the Substantia Nigra

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Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter implicated in the control of generalized seizures induced by various convulsants. A specific anatomical site of action, the substantia nigra (SN), has been shown to be involved in the GABA mediation of seizures. It was the objective of this study to investigate the GABA system in the SN and its response to seizures induced by the neuroexcitant kainic acid (KA). Since there have been conflicting reports of the effects of convulsants on GABA-related measures in some brain regions, with some reporting increases and others showing decreases, one purpose of this investigation was to examine the directionality of changes in GABA content of the SN, along with the magnitude of the effects of KA and the time course over which these effects were manifested. Rats were injected intraperitoneally with either 12.5 mg/kg KA or saline. GABA and protein contents of the SN were measured at 2, 16, 24 and 48 hrs subsequent to injection. The levels of GABA in the SN were found to increase in KA-injected animals over control levels for all time intervals except the 16 hr condition. These results are generally in conflict with those obtained by many researchers using the activity of the GABA synthetic enzyme glutamic acid decarboxylase (GAD) as a measure of GABA levels. It is suggested that GABA levels may actually increase in response to convulsants and serve to negatively feed back to its synthetic enzyme. Therefore, a decrease in GAD activity would not necessarily reflect a decrease in GABA levels. Future research directions include enzyme studies of both GAD and GABA transaminase and their regulation by products and substrates.


Author Institution: Department of Biological Sciences, Bowling Green State University



The Ohio Journal of Science. v89, n4 (September, 1989), 95-97