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Cellular compartments of GABA in brain and their relationship to anticonvulsant activity

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Summary

The effects of GABA-elevating agents were examined with respect to the cellular compartments in which GABA increases occurred and the brain region(s) that mediate the anticonvulsant activity of these compounds. Changes in GABA occurring in the presence and absence of GABAergic nerve terminals were estimated in vivo using rats in which the GABA projection to the substantia nigra (SN) was destroyed on one side of the brain. One week post-operatively, the GABA concentration in the denervated SN was 10–20% of control. The net increase in GABA content of the denervated SN was compared to that of the intact SN after intraperitoneal injection of amino-oxacetic acid (AOAA), di-n-propylacetate (DPA) and γ-vinyl GABA (GVG). In the intact SN, all drugs produced significant increases in GABA. In the denervated SN, both AOAA and GVG produced marked increases in GABA (nearly equivalent to those obtained in the intact SN) whereas DPA was without effect. It therefore appears that the DPA-induced elevation of GABA depends upon the presence of GABAergic nerve terminals whereas AOAA and GVG primarily elevate GABA in non-nerve terminal compartments. An increase in GABA associated with nerve terminals was obtained with GVG only after a latency of more than 12 h following a single injection. The time course of elevation of nerve terminal-associated GABA coincided with the time course of anticonvulsant action of GVG; both effects were maximal at 60 h after a single injection. Taken together, our results indicate that the ability of DPA, AOAA and GVG to protect against chemically- and electrically-induced seizures is directly correlated with increases in nerve terminal GABA and not related to increases in other GABA compartments.

Localization of the anatomical site that mediates anticonvulsant activity was examined using intracerebral injections of GVG into fore-, mid-and hindbrain areas. Blockade of tonic hindlimb extension in the maximal electroshock test and blockade of tonic and clonic seizures produced by pentylenetetrazol and bicuculline was obtained by microinjection of GVG (10 µg) into the ventral tegmental area of the midbrain. Injections of GVG (10–40 µg) into forebrain areas (striatum, thalamus) or into hindbrain (pontine tegmentum) were without anticonvulsant activity. Anticonvulsant effects of midbrain GVG were correlated with GABA elevation (3–4 fold) within a 1.5 mm radius of the injection site; these effects were obtained within 6 h and lasted three to four days after a single treatment. After four days seizure activity returned to control. No changes in spontaneous motor activity or reflexes accompanied the GVG injections. Similar but shorter lasting anticonvulsant effects were obtained with the direct GABA receptor agonist muscimol (50 ng) injected into the midbrain site. On the other hand, doses of muscimol up to 500 ng placed in the rostral pontine tegmentum were without anticonvulsant effect, despite the appearance of marked sedation.

The time to peak anticonvulsant activity after midbrain microinjection of GVG (6 h) was considerably more rapid than that after intraperitoneal injection (60 h). Compartmental analysis revealed that nerve terminal associated GABA was elevated by 6 h after GVG when the direct microinjection route was used. These results suggest that GABAergic synapses in the midbrain may be critically involved in the control of seizure propagation.

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References

  1. DeFeudis, F. V. & Mandel, P., 1981. Amino Acid Neurotransmitters; Adv. in Biochem. Psychopharmacol. Vol. 29, Raven Press, New York.

    Google Scholar 

  2. Costa, E., DiChiara, G. & Gessa, G. L., 1981. GABA and Benzodiazepine Receptors, Adv. in Biochem. Psychopharmacol. Vol. 26, Raven Press, New York.

    Google Scholar 

  3. Lal, H., 1980. GABA Neurotransmission, Brain Res. Bull. 5: Suppl 2.

  4. Bartholini, G., Scatton, B., Zivkovic, B. & Lloyd, K. G., 1979. GABA-Neurotransmitters (Krogsgaard-Larsen, P., Scheel-Kruger, J. & Kofod, H., eds) Academic Press, New York, pp. 326–334.

  5. Johnston, G. A. R., Allan, R. D., Kennedy, S. M. E. & Twitchin, B., 1979. (Krogsgaard-Larsen, P., Scheel-Kruger, J. & Kofod, H., eds) Academic Press, New York, pp. 149–168.

  6. Krogsgaard-Larsen, P. & Johnston, G. A. R., 1978. J. Neurochem. 30: 1377–1382.

    PubMed  Google Scholar 

  7. Enna, S. J. & Maggi, A., 1979. Life Sci. 24: 1727–1738.

    PubMed  Google Scholar 

  8. Chrystal, E., Bey, P. & Rando, R. R., 1979. J. Neurochem. 32: 1501–1507.

    PubMed  Google Scholar 

  9. Metcalf, B. W., 1979. Biochem. Pharmacol. 28: 1705–1712.

    PubMed  Google Scholar 

  10. Schousboe, A., Thorbek, P., Hertz, L. & Krogsgaard-Larsen, P., 1979. J. Neurochem. 33: 181–189.

    PubMed  Google Scholar 

  11. Brehm, L., Krogsgaard-Larsen, P. & Jacobsen, P., 1979. GABA-Neurotransmitters (Krogsgaard-Larsen, P., Scheel-Kruger, J. & Kofod, H., eds) Academic Press, New York, pp. 247–262.

  12. Grandison, L. & Guidotti, A., 1977. Neuropharmacol. 16: 533–536.

    Google Scholar 

  13. DiMicco, J. A., Gale, K., Hamilton, B. & Gillis, R. A., 1979. Science 204: 1106–1109.

    PubMed  Google Scholar 

  14. Scheel-Kruger, J., Arnt, J. & Magelund, G., 1977. Neurosci. Lett. 4: 351–354.

    Google Scholar 

  15. Grandison, L. & Guidotti, A., 1979. Endocrinology 105: 754–759.

    PubMed  Google Scholar 

  16. Baxter, C. F., 1976. GABA in Nervous System Function. (Roberts, E., Chase, T. N. & Tower, D. B., eds) Raven Press, New York, pp. 61–87.

  17. Iversen, L. L., 1978. Psychopharmacology: A Generation of Progress (Lipton, M. A., DiMascio, A. & Killam, K. F., eds) Raven press, New York, pp. 25–38.

  18. Awapara, J., Landua, A. J., Fuerst, R. & Seale, B., 1950. J. Biol. Chem. 187: 35–39.

    PubMed  Google Scholar 

  19. Roberts, E. & Frankel, S., 1950. J. Biol. Chem. 187: 55–63.

    PubMed  Google Scholar 

  20. Bazemore, A. W., Elliott, K. A. C. & Florey, E., 1956. Nature 178: 1052–1053.

    PubMed  Google Scholar 

  21. Bazemore, A. W., Elliott, K. A. C. & Florey, E., 1957. J. Neurochem. 1: 334–339.

    PubMed  Google Scholar 

  22. Hayashi, T., 1959. J. Physiol. 145: 570–578.

    PubMed  Google Scholar 

  23. Purpura, D. P., Girado, M., Smith, T. G., Callan, D. A. & Grundfest, H., 1959. J. Neurochem. 3: 238–268.

    PubMed  Google Scholar 

  24. Eidelberg, E., Baxter, C. F., Roberts, E. & Saldias, C. A., 1960. Inhibition in the Nervous System and γ-Aminobutyric Acid (Roberts, E., Baxter, C. F., Van Harreveld, A., Wiersma, C. A. G., Adey, R. & Killam, K. F., eds) Pergamon Press, New York, pp. 365–370.

  25. Tower, D. B., 1960. Inhibition in the Nervous System and γ-Aminobutyric Acid (Roberts, E., Baxter, C. F., Van Harreveld, A., Wiersma, C. A. G., Adey, R. & Killam, K. F. eds) Pergamon Press, New York, pp. 562–578.

  26. Van Gelder, N. M. & Elliott, K. A. C., 1958. J. Neurochem. 3: 139–143.

    PubMed  Google Scholar 

  27. Killam, K. F. & Bain, J. A., 1957. J. Pharmacol. Exp. Ther. 119: 255–262.

    PubMed  Google Scholar 

  28. Coursin, D. B., 1960. Inhibition in the Nervous System and γ-Aminobutyric Acid (Roberts, E., Baxter, C. F., Van Harreveld, A., Wiersma, C. A. G., Adey, W. R. & Killam, K. F. eds) Pergamon Press, New York, pp. 294–301.

  29. Tower, D. B., 1958. Nutrition Rev. 16: 161–164.

    Google Scholar 

  30. Reilly, R. H., Killam, K. F., Jenney, E. H., Marshall, W. H., Tausig, T., Apter, N. S. & Pfeiffer, C. C., 1953. J. Am. Med. Assoc. 152: 1317–1321.

    PubMed  Google Scholar 

  31. Kelly, J. S. & Beart, P. M., 1975. Handbook of Psychopharmacol. (Iversen, L. L., Iversen, S. D. & Snyder, S. H., eds.) Vol. 4, Plenum Press, New York, pp. 129–209.

  32. Ryall, R. W., 1975. Handbook of Psychopharmacol. (Iversen, L. L., Iversen, S. D. & Snyder, S. H., eds.) Vol. 4, plenum Press, New York, pp. 83–128.

  33. Baxter, C. F. & Roberts, E., 1959. Proc. Soc. Exp. Biol. and Med. 101: 811–815.

    Google Scholar 

  34. Baxter, C. F. & Roberts, E., 1961. J. Biol. Chem. 236: 3287–3294.

    PubMed  Google Scholar 

  35. Tapia, R., 1975. Handbook of Psychopharmacol. (Iversen, L. L. Iversen, S. D. & Snyder, S. H., eds.), Vol. 4, Plenum Press, New York, pp. 1–58.

  36. Roberts, E. & Eidelberg, E., 1960. Internatl. Rev. Neurobiol. 2: 279–331.

    Google Scholar 

  37. Roberts, E., Wein, J. & Simonsen, D. G., 1964. Vitamins and Hormones 22: 503–559.

    PubMed  Google Scholar 

  38. Cooper, J. R., Bloom, F. E. & Roth, R. H., 1978. The Biochemical Basis of neuropharmacology, Oxford Univ. Press, new York, pp. 223–258.

    Google Scholar 

  39. Wallach, D. P., 1961. Biochem. Pharmacol. 5: 323–331.

    PubMed  Google Scholar 

  40. Tapia, R., Pasantes, H., Perez de la Mora, M., Ortega, B. G. & Massieu, G. H., 1967.

  41. Loscher, W. & Frey, H. H., 1978. Biochem. Pharmacol. 27: 103–108.

    PubMed  Google Scholar 

  42. Kuriyama, K., Roberts, E. & Rubenstein, M. K., 1966. Biochem. Pharmacol. 15: 221–236.

    PubMed  Google Scholar 

  43. Wood, J. D. & Peesker, S. J., 1973. J. Neurochem. 20: 379–387.

    PubMed  Google Scholar 

  44. Rando, R. R., 1974. Science 185: 320–324.

    PubMed  Google Scholar 

  45. Fowler, L. J. & John, R. A., 1972. Biochem. J. 130: 569–573.

    PubMed  Google Scholar 

  46. Jung, M. J. & Metcalf, B. W., 1975. Biochem. Biophys. Res. Comm.

  47. Rando, R. R. & Bangerter, F. W., 1976. J. Am. Chem. Soc. 98: 6762–6764.

    PubMed  Google Scholar 

  48. Kobayashi, K., Miyazawa, S. & Terahara, A., 1976. Tetrahedron Lett. 7: 537–540.

    Google Scholar 

  49. Matsui, Y. & Deguchi, T., 1977. Life Sci. 20: 1291–1296.

    PubMed  Google Scholar 

  50. Jung, M. J., Lippert, B., Metcalf, B. W., Schechter, P. J., Bohlen, P. & Sjoerdsma, A., 1977. J. Neurochem. 28: 717–723.

    PubMed  Google Scholar 

  51. Lippert, B., Metcalf, B. W., Jung, M. J. & Casara, P., 1977. Eur. J. Biochem. 74: 441–445.

    PubMed  Google Scholar 

  52. Schechter, P. J., Trainer, Y., Jung, M. J. & Bohlen, P., 1977. Eur. J. Pharmacol. 45: 319–328.

    PubMed  Google Scholar 

  53. Loscher, W., 1980. J. Neurochem. 34: 1603–1608.

    PubMed  Google Scholar 

  54. Godin, Y., Heiner, L., Mark, J. & Mandel, P., 1969. J. Neurochem. 16: 869–873.

    PubMed  Google Scholar 

  55. Simler, S., Ciesielski, L., Maitre, M., Randrianarisoa, H. & Mandel, P., 1973. Biochem. Pharmacol. 22: 1701–1708.

    PubMed  Google Scholar 

  56. Fowler, L. J., Beckford, J. & John, R. A., 1975. Biochem. Pharmacol. 24: 1267–1270.

    PubMed  Google Scholar 

  57. Harvey, P. K. P., Bradford, H. F. & Davison, A. N., 1975. FEBS Lett. 52: 251–254.

    PubMed  Google Scholar 

  58. Whittle, S. R. & Turner, A. J., 1978. J. Neurochem. 31: 1453–1459.

    PubMed  Google Scholar 

  59. Kaufman, E. E., Nelson, T., Goochee, C. & Sokoloff, L., 1979. J. Neurochem. 32: 699–712.

    PubMed  Google Scholar 

  60. Ciesielski, L., Maitre, M., Cash, C. & Mandel, P., 1975. Biochem. Pharmacol. 24: 1055–1058.

    PubMed  Google Scholar 

  61. Dickinson, R. G., Harland, R. C., Ilias, A. M., Rodgers, R. M., Kaufman, S. N., Lynn, R. K. & Gerber, N., 1979. J. Pharmacol. Exp. Ther. 211: 583–595.

    PubMed  Google Scholar 

  62. Albertson, T. E., Peterson, S. L., Stark, L. G. & Baselt, R. C., 1981. Neuropharmacol. 20: 95–97.

    Google Scholar 

  63. Schechter, P. J., Trainer, Y. & Grove, J., 1978. J. Neurochem. 31: 1325–1327.

    PubMed  Google Scholar 

  64. Perry, T. L. & Hansen, S., 1978. J. Neurochem. 30: 679–684.

    PubMed  Google Scholar 

  65. Kukino, K. & Deguchi, T., 1977. Chem. Pharm. Bull. 25: 2257–2261.

    PubMed  Google Scholar 

  66. Perry, T. L. & Hansen, S., 1973. J. Neurochem. 21: 1167–1175.

    PubMed  Google Scholar 

  67. Perry, T. L., Urquhart, N., Hansen, S. & Kennedy, J., 1974. J. Neurochem. 23: 443–445.

    PubMed  Google Scholar 

  68. Perry, T. L., Kish, S. J. & Hansen, S., 1979. J. Neurochem. 32: 1641–1645.

    PubMed  Google Scholar 

  69. Seiler, N., Bink, G. & Grove, J., 1979. Neurochem. Res. 4: 425–435.

    PubMed  Google Scholar 

  70. Seiler, N., Bink, G. & Grove, J., 1980. Neuropharmacol. 19: 251–258.

    Google Scholar 

  71. Kuriyama, K., Roberts, E. & Rubinstein, M. K., 1966. Biochem. Pharmacol. 15: 221–236.

    PubMed  Google Scholar 

  72. Wood, J. D. & Peesker, S. J., 1975. J. Neurochem. 25: 277–282.

    PubMed  Google Scholar 

  73. Lust, W. D., Kupferberg, H. J., Yonekawa, W. D., Penry, J. K., Passoneau, J. V. & Wheaton, A. B., 1978. Molec. Pharmacol. 14: 347–356.

    Google Scholar 

  74. Horton, R. W., Anlezark, G. M., Sawaya, M. C. B. & Meldrum, B. S., 1977.

  75. Goldstein, D. B., 1979. J. Pharmacol. Exp. Ther. 208: 223–227.

    PubMed  Google Scholar 

  76. Meldrum, B. S., Anlezark, G. M., Ashton, C. G., Horton, R. W. & Sawaya, M. C. B., 1977. Post-traumatic Epilepsy, Pharmacological Prophylaxis of Epilepsy (Majkowski, J., ed.) pp. 139–153.

  77. Stone, W. E., 1977. Epilepsia 18: 507–514.

    PubMed  Google Scholar 

  78. Wood, J. D., Durham, J. S. & Peesker, S. J., 1977. Neurochem. Res. 2: 707–715.

    Google Scholar 

  79. Simon, D. & Penry, J. K., 1975. Epilepsia 16: 549–573.

    PubMed  Google Scholar 

  80. Schechter, P. J., Tranier, Y., Jung, M. J., Sjoerdsma, A., 1977. J. Pharmacol. Exp. Ther. 201: 606–612.

    PubMed  Google Scholar 

  81. Schechter, P. J. & Trainer, Y., 1977. Psychopharmacol. 54: 145–148.

    Google Scholar 

  82. Schechter, P. J. & Trainer, Y., 1978. Enzyme-Activated Irreversible Inhibitors (Seiler, N., Jung, M. J. & Koch-Weser, J., eds.) Elsevier, Amsterdam, pp. 149–162.

  83. Loscher, W., 1980. N.S. Arch. Pharmacol. 315: 119–128.

    Google Scholar 

  84. Iadarola, M. J., Raines, A. R. & Gale, K., 1979. J. Neurochem. 33: 1119–1123.

    PubMed  Google Scholar 

  85. Gale, K. & Iadarola, M. J., 1980. Science 208: 288–291.

    PubMed  Google Scholar 

  86. Baxter, C. F. & Roberts, E., 1960. Proc. Soc. Exp. Biol. Med. 104: 426–427.

    PubMed  Google Scholar 

  87. DaVanzo, J. P., Greig, M. E. & Cronin, M. A., 1961. Am. J. Physiol. 201: 833–837.

    PubMed  Google Scholar 

  88. Roa, D. P., Tews, J. K. & Stone, W. E., 1964. Biochem. Pharmacol. 13: 477–487.

    PubMed  Google Scholar 

  89. Murakami, Y., Abe, M. & Murakami, K., 1976. J. Neurochem. 26: 655–656.

    PubMed  Google Scholar 

  90. Maynert, E. W. & Kaji, H. K., 1962. J. Pharmacol. Exp. Ther. 137: 114–121.

    PubMed  Google Scholar 

  91. Abe, M. & Matsuda, M., 1977. J. Biochem. 82: 195–200.

    PubMed  Google Scholar 

  92. Wood, J. D., Russell, M. P., Kurylo, E. & Newstead, J. D., 1979. J. Neurochem. 33: 61–68.

    PubMed  Google Scholar 

  93. Wood, J. D., 1975. Prog. in Neurobiol. 5: 77–95.

    Google Scholar 

  94. Okada, YU., Nitsch-Hassler, C., Kim, J. S., Bak, I. J. & Hassler, R., 1971. Exp. Brain Res. 14: 514–518.

    Google Scholar 

  95. Fahn, S. & Cote, L. J., 1968. J. Neurochem. 15: 209–213.

    PubMed  Google Scholar 

  96. Tappaz, M. L., Brownstein, M. J. & Palkovits, M., 1976. Brain Res. 108: 371–379.

    PubMed  Google Scholar 

  97. Massari, V. J., Gottesfeld, Z. & Jacobowitz, D. M., 1976. Brain Res. 118: 147–151.

    PubMed  Google Scholar 

  98. Tappaz, M. L., Brownstein, M. J. & Kopin, I. J., 1977. Brain Res. 125: 109–121.

    PubMed  Google Scholar 

  99. van der Heyden, J. A. M. & Korf, J., 1979. J. Neurochem. 33:857–861.

    PubMed  Google Scholar 

  100. Albers, R. W. & Brady, R. O., 1959. J. Biol. Chem. 234: 926–928.

    PubMed  Google Scholar 

  101. Enna, S. J., Kuhar, M. J. & Snyder, S. H., 1975. Brain Res. 43: 168–174.

    Google Scholar 

  102. Placheta, P. & Karobath, M., 1979. Brain Res. 178: 580–583.

    PubMed  Google Scholar 

  103. DeFeudis, F. V., 1977. Prog. in Neurobiol. 9: 123–145.

    Google Scholar 

  104. Kilpatrick, I. C., Starr, M. S., Fletcher, A., James, T. A. & MacLeod, N. K., 1980. Exp. Brain Res. 40: 45–54.

    PubMed  Google Scholar 

  105. MacLeod, N. K., James, T. A., Kilpatrick, I. C. & Starr, M. S., 1980. Exp. Brain Res. 40: 55–61.

    PubMed  Google Scholar 

  106. Vincent, S. R., Hattori, T. & McGeer, E. G., 1978. Brain Res. 151: 159–164.

    PubMed  Google Scholar 

  107. Hertz, L., 1979. Prog. in Neurobiol. 13: 277–323.

    Google Scholar 

  108. Fonnum, F. & Walberg, F., 1973. Brain Res. 54: 115–127.

    PubMed  Google Scholar 

  109. Schon, F. & Kelly, J. S., 1974. Brain Res. 66: 275–288.

    Google Scholar 

  110. Iversen, L. L., Dick, F., Kelly, J. S. & Schon, F., 1975. Metabolic Compartmentation and Neurotransmission (Berl, S., Clarke, D. D. & Schneider, D., eds) Plenum Press, new York, pp. 65–89.

  111. Hutchinson, H. T., Werrbach, K., Vance, C. & Haber, B., 1974. Brain Res. 66: 265–274.

    Google Scholar 

  112. Lodge, D., Curtis, D. R. & Johnston, G. A. R., 1978. J. Neurochem. 31: 1525–1528.

    PubMed  Google Scholar 

  113. Yarbrough, G. G., 1978. Can. J. Physiol. Pharmacol. 56: 443–446.

    PubMed  Google Scholar 

  114. Frey, H. H., Popp, C. & Loscher, W., 1979. Neuropharmacol. 18: 581–590.

    Google Scholar 

  115. Kuriyama, K., 1976. GABA in Nervous System Function (Roberts, E., Chase, T. N. & Tower, D. B., eds) Raven Press, New York, pp. 187–196.

  116. Barber, R. & Saito, K., 1976. GABA in Nervous System Function (Roberts, E., Chase, T. N. & Tower, D. B., eds) Raven Press, New York, pp. 113–132.

  117. Van Gelder, N. M., 1965. J. Neurochem. 12: 231–237.

    PubMed  Google Scholar 

  118. Hyde, J. C. & Robinson, N., 1974. J. Neurochem. 23: 365–367.

    PubMed  Google Scholar 

  119. Schwarcz, R., Bennett, J. P. & Coyle, J. T., 1977. Ann. Neurol. 2: 299–303.

    PubMed  Google Scholar 

  120. Wu, P. H., Durden, D. A. & Hertz, L., 1979. J. Neurochem. 32: 379–390.

    PubMed  Google Scholar 

  121. Kohl, R. L., Quay, W. B. & Perez-Polo, J. R., 1980. J. Neurochem. 34: 1792–1795.

    PubMed  Google Scholar 

  122. Toman, J. E P., Swinyard, E. A. & Goodman, L. S., 1946. J. Neurophysiol. 9: 231–239.

    Google Scholar 

  123. Woodbury, L. A. & Davenport, V. D., 1952. Arch. Int. Pharmacodyn. 92: 97–107.

    PubMed  Google Scholar 

  124. Krall, R. L., Penry, J. K., White, B. G., Kupferberg, H. J. & Swinyard, E. A., 1978. Epilepsia 19: 409–428.

    PubMed  Google Scholar 

  125. Coyle, J. T., Molliver, M. E. & Kuhar, M. J., 1978. J. Comp. Neurol. 180: 301–324.

    PubMed  Google Scholar 

  126. Zaczek, R., Schwarcz, R. & Coyle, J. T., 1978. Brain Res. 152: 626–632.

    PubMed  Google Scholar 

  127. Schwarcz, R. & Coyle, J. T., 1977. Brain Res. 127: 235–249.

    PubMed  Google Scholar 

  128. Kim, J. S., Bak, I. J., Hassler, R. & Okada, Y., 1971. Exp. Bain Res. 14: 95–104.

    Google Scholar 

  129. Hattori, T., McGeer, P. L., Fibiger, H. C. & McGeer, E. G., 1973. Brain Res. 54: 103–114.

    PubMed  Google Scholar 

  130. Fonnum, F., Gottesfeld, Z. & Grofova, I., 1978. Brain Res. 143: 125–138.

    PubMed  Google Scholar 

  131. Ribak, C. E., Vaughn, J. E. & Roberts, E., 1980. Brain Res. 192: 413–420.

    PubMed  Google Scholar 

  132. Gale, K. & Iadarola, M. J., 1980. Brain Res. 183: 217–223.

    PubMed  Google Scholar 

  133. Pycock, C. J., 1980. Neurosci. 5: 461–514.

    Google Scholar 

  134. Bun, N. T. & Van Gelder, N. M., 1974. Br. J. Pharmacol. 52: 401–406.

    PubMed  Google Scholar 

  135. Knjevic, K. & Schwarcz, S., 1968. Structure and Function of Inhibitory Neural Mechanisms (Von Euler, S., Skoglund, S. & Soderberg, U., eds.) Pergamon Press, New York, pp. 419–427.

  136. Guidotti, A., Gale, K., Suria, A. & Toffano, G., 1979. Brain Res. 172: 566–571.

    PubMed  Google Scholar 

  137. Waddington, J. L. & Cross, A. J., 1978. Nature 276: 618–620.

    PubMed  Google Scholar 

  138. Iadarola, M. J. & Gale, K., 1979. Eur. J. Pharmacol. 59: 125–129.

    PubMed  Google Scholar 

  139. Beart, P. M., Kelly, J. S. & Schon, F., 1974. Biochem. Soc. Transac. 2: 266–268.

    Google Scholar 

  140. Waniewski, R. A. & Suria, A., 1977. Life Sci. 21: 1129–1142.

    PubMed  Google Scholar 

  141. Wood, J. D., Kurylo, E. & Newstead, J. D., 1978. Can. J. Biochem. 56: 667–672.

    PubMed  Google Scholar 

  142. Sarhan, S. & Seiler, N., 1979. J. Neurosci. Res. 4: 398–421.

    Google Scholar 

  143. Bell, J. A. & Anderson, E. G., 1974. Neuropharmacol. 13: 885–894.

    Google Scholar 

  144. Gottesfeld, Z., Kelly, J. S. & Renaud, L. P., 1972. Brain Res. 11: 319–335.

    Google Scholar 

  145. ladarola, M. J. & Gale, K., 1980. Brain Res. Bull. 5: Suppl. 2. pp. 13–19.

    PubMed  Google Scholar 

  146. Palfreyman, M. G., Huot, S., Lippert, B. & Schechter, P. J., 1979. GABA-Neurotransmitters (Krogsgaard-Larsen, P., Scheel-Kruger, J. & Kofod, H., eds.) Academic Press, New York, pp. 432–446.

  147. Gale, K. & Iadarola, M. J., 1980. Eur. J. Pharmacol. 68: 233–235.

    PubMed  Google Scholar 

  148. Collins, R. C., McLean, M. & Olney, J., 1980. Life Sci. 27: 855–862.

    PubMed  Google Scholar 

  149. Faeth, W. H., Walker, A. E. & Andy, O. J., 1954. Epilepsia, 3rd Series, 3: 37–48.

    Google Scholar 

  150. Casu, M. & Gale, K., 1981. Life Sci., 29: 681–688.

    PubMed  Google Scholar 

  151. Nicklas, W. J., Nunez, R., Berl, S. & Duvoisin, R., 1979. J. Neurochem. 33: 839–844.

    PubMed  Google Scholar 

  152. Casu, M. & Gale, K., 1981. J. Pharmacol. Exp. Ther. 217: 177–180.

    PubMed  Google Scholar 

  153. Casu, M. & Gale, K., 1981. Fed. Proc., 40: 290.

    Google Scholar 

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  1. Michael J. Iadarola

    Present address: Duke VA Neurology Research Laboratory, VA Hospital, Durham, N.C., USA

Authors and Affiliations

  1. Dept. of Pharmacology, Georgetown University Schools of Medicine and Dentistry, Washington, D.C., USA

    Michael J. Iadarola & Karen Gale

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  1. Michael J. Iadarola
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  2. Karen Gale
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Iadarola, M.J., Gale, K. Cellular compartments of GABA in brain and their relationship to anticonvulsant activity. Mol Cell Biochem 39, 305–329 (1981). https://doi.org/10.1007/BF00232582

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  • DOI: https://doi.org/10.1007/BF00232582

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