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Alterations of GABA metabolism and seizure susceptibility in the substantia nigra of the kindled rat acclimating to changes in osmotic state

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Abstract

Seizure susceptibility and GABA metabolism were altered in the substantia nigra [SN] of adult male Sprague Dawley rats when these animals were acclimating to an altered plasma osmolality. Changes in GABA metabolism were measured in vivo in SN of the freely moving rat. Suitable precautions were taken to avoid any post-mortem flux of glutamate to GABA and to correct for the underestimation of GABA build up in SN due to the finite diffusion rate of γ-vinyl GABA [GVG] after stereotaxic injection of small amounts into one side of the brain. Control experiments provided evidence that changes in osmolality, within a normal physiological range, did not affect significantly γ-aminobutyric acid transaminase [GABA-T]. Also kindling via the medial septum [MS], in the absence of electrical stimulation did not alter GABA metabolism in SN, thus providing a stable baseline for studies of osmotic effects. Hyperosmolality was associated with a rise in seizure thresholds, with a marked reduction of the rate of GABA synthesis in SN, and with a substantial increase in turnover time of the GABA pool. Hypoosmolality, of a degree known to be associated with mild cerebral edema and swelling localized to astrocytes, markedly reduced seizure threshold, and reduced GABA pool size in SN, but did not alter the rate of GABA synthesis significantly. These results demonstrate by new and independent means the relationship between GABA metabolism in the SN and seizure susceptibility in vivo.

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Authors and Affiliations

  1. Neurochemistry Laboratory, V.A. Medical Center, 91343, Sepulveda, California

    Claude F. Baxter, Charles C. Oh, Louise K. Ozaki & Roger A. Baldwin

  2. Epilepsy Laboratory, V.A. Medical Center, 91343, Sepulveda, California

    Claude G. Wasterlain

  3. Department of Psychiatry and Biobehavioral Sciences, UCLA Medial Center, 90024-1761, Los Angeles, California

    Claude F. Baxter

  4. Department of Neurology, UCLA Medial Center, 90024-1761, Los Angeles, California

    Claude G. Wasterlain

  5. Brain Research Institute and Neuropsychiatric Institute, Center for Health Sciences, UCLA, 90024-1761, Los Angeles, California

    Claude F. Baxter & Claude G. Wasterlain

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Special issue dedicated to Dr. Eugene Roberts.

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Baxter, C.F., Oh, C.C., Wasterlain, C.G. et al. Alterations of GABA metabolism and seizure susceptibility in the substantia nigra of the kindled rat acclimating to changes in osmotic state. Neurochem Res 16, 269–278 (1991). https://doi.org/10.1007/BF00966090

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