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

  • Michael J. Iadarola
  • Karen Gale
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 1)

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.

Keywords

Substantia Nigra Superior Colliculus Anticonvulsant Effect Gaba Level Maximal Electroshock Seizure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    DeFeudis, F. V. & Mandel, P., 1981. Amino Acid Neuro-transmitters; Adv. in Biochem. Psychopharmacol. Vol. 29, Raven Press, New York.Google Scholar
  2. 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. 3.
    Lai, H., 1980. GABA Neurotransmission, Brain Res. Bull. 5: Suppl 2.Google Scholar
  4. 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.Google Scholar
  5. 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.Google Scholar
  6. 6.
    Krogsgaard-Larsen, P. & Johnston, G. A. R., 1978. J. Neurochem. 30: 1377–1382.PubMedGoogle Scholar
  7. 7.
    Enna, S. J. & Maggi, A., 1979. Life Sci. 24: 1727–1738.PubMedGoogle Scholar
  8. 8.
    Chrystal, E., Bey, P. & Rando, R. R., 1979. J. Neurochem. 32: 1501–1507.PubMedGoogle Scholar
  9. 9.
    Metcalf, B. W., 1979. Biochem. Pharmacol. 28: 1705–1712.PubMedGoogle Scholar
  10. 10.
    Schousboe, A., Thorbek, P., Hertz, L. & Krogsgaard-Larsen, P., 1979. J. Neurochem. 33: 181–189.PubMedGoogle Scholar
  11. 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.Google Scholar
  12. 12.
    Grandison, L. & Guidotti, A., 1977. Neuropharmacol. 16: 533–536.Google Scholar
  13. 13.
    DiMicco, J. A., Gale, K., Hamilton, B. & Gillis, R. A., 1979. Science 204: 1106–1109.PubMedGoogle Scholar
  14. 14.
    Scheel-Kruger, J., Arnt, J. & Magelund, G., 1977. Neurosci. Lett. 4: 351–354.PubMedGoogle Scholar
  15. 15.
    Grandison, L. & Guidotti, A., 1979. Endocrinology 105: 754–759.PubMedGoogle Scholar
  16. 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.Google Scholar
  17. 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.Google Scholar
  18. 18.
    Awapara, J., Landua, A. J., Fuerst, R. & Seale, B., 1950. J. Biol. Chem. 187: 35–39.PubMedGoogle Scholar
  19. 19.
    Roberts, E. & Frankel, S., 1950. J. Biol. Chem. 187: 55–63.PubMedGoogle Scholar
  20. 20.
    Bazemore, A. W., Elliott, K. A. C. & Florey, E., 1956. Nature 178: 1052–1053.PubMedGoogle Scholar
  21. 21.
    Bazemore, A. W., Elliott, K. A. C. & Florey, E., 1957. J. Neurochem. 1: 334–339.Google Scholar
  22. 22.
    Hayashi, T., 1959. J. Physiol. 145: 570–578.PubMedGoogle Scholar
  23. 23.
    Purpura, D. P., Girado, M., Smith, T. G., Callan, D. A. & Grundfest, H., 1959. J. Neurochem. 3: 238–268.PubMedGoogle Scholar
  24. 24.
    Eidelberg, E., Baxter, C. F., Roberts, E. & Saldias, C. A., 1960. Inhibition in the Nervous System and y-Amino-butyric 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.Google Scholar
  25. 25.
    Tower, D. B., 1960. Inhibition in the Nervous System and y-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.Google Scholar
  26. 26.
    Van Gelder, N. M. & Elliott, K. A. C., 1958. J. Neurochem. 3: 139–143.Google Scholar
  27. 27.
    Killam, K. F. & Bain, J. A., 1957. J. Pharmacol. Exp. Ther. 119: 255–262.PubMedGoogle Scholar
  28. 28.
    Coursin, D. B., 1960. Inhibition in the Nervous System and y-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.Google Scholar
  29. 29.
    Tower, D. B., 1958. Nutrition Rev. 16: 161–164.Google Scholar
  30. 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.Google Scholar
  31. 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.Google Scholar
  32. 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.Google Scholar
  33. 33.
    Baxter, C. F. & Roberts, E., 1959. Proc. Soc. Exp. Biol, and Med. 101: 811–815.Google Scholar
  34. 34.
    Baxter, C. F. & Roberts, E., 1961. J. Biol. Chem. 236: 3287–3294.PubMedGoogle Scholar
  35. 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.Google Scholar
  36. 36.
    Roberts, E. & Eidelberg, E., 1960. Internati. Rev. Neurobiol. 2: 279–331.Google Scholar
  37. 37.
    Roberts, E., Wein, J. & Simonsen, D. G., 1964. Vitamins and Hormones 22: 503–559.PubMedGoogle Scholar
  38. 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. 39.
    Wallach, D. P., 1961. Biochem. Pharmacol. 5: 323–331.PubMedGoogle Scholar
  40. 40.
    Tapia, R., Pasantes, H., Perez de la Mora, M., Ortega, B. G. & Massieu, G. H., 1967.Google Scholar
  41. 41.
    Loscher, W. & Frey, H.H., 1978. Biochem. Pharmacol. 27: 103–108.PubMedGoogle Scholar
  42. 42.
    Kuriyama, K., Roberts, E. & Rubenstein, M. K., 1966. Biochem. Pharmacol. 15: 221–236.PubMedGoogle Scholar
  43. 43.
    Wood, J. D. & Peesker, S. J., 1973. J. Neurochem. 20: 379–387.PubMedGoogle Scholar
  44. 44.
    Rando, R. R., 1974. Science 185: 320 - 324.PubMedGoogle Scholar
  45. 45.
    Fowler, L. J. & John, R. A., 1972. Biochem. J. 130: 569–573.Google Scholar
  46. 46.
    Jung, M. J. & Metealf, B. W., 1975. Biochem. Biophys. Res. Comm.Google Scholar
  47. 47.
    Rando, R. R. & Bangerter, F. W., 1976. J. Am. Chem. Soc. 98: 6762–6764.PubMedGoogle Scholar
  48. 48.
    Kobayashi, K., Miyazawa, S. & Terahara, A., 1976. Tetrahedron Lett. 7: 537–540.Google Scholar
  49. 49.
    Matsui, Y. & Deguchi, T., 1977. Life Sci. 20: 1291–1296.PubMedGoogle Scholar
  50. 50.
    Jung, M. J., Lippert, B., Metealf, B. W., Schechter, P. J., Bohlen, P. & Sjoerdsma, A., 1977. J. Neurochem. 28: 717–723.PubMedGoogle Scholar
  51. 51.
    Lippert, B., Metealf, B. W., Jung, M. J. & Casara, P., 1977. Eur. J. Biochem. 74: 441–445.PubMedGoogle Scholar
  52. 52.
    Schechter, P. J., Trainer, Y., Jung, M. J. & Bohlen, P., 1977. Eur. J. Pharmacol. 45: 319–328.PubMedGoogle Scholar
  53. 53.
    Loscher, W., 1980. J. Neurochem. 34: 1603–1608.PubMedGoogle Scholar
  54. 54.
    Godin, Y., Heiner, L., Mark, J. & Mandel, P., 1969. J. Neurochem. 16: 869–873.PubMedGoogle Scholar
  55. 55.
    Simler, S., Ciesielski, L., Maitre, M., Randrianarisoa, H. & Mandel, P., 1973. Biochem. Pharmacol. 22: 1701–1708.PubMedGoogle Scholar
  56. 56.
    Fowler, L. J., Beckford, J. & John, R. A., 1975. Biochem. Pharmacol. 24: 1267–1270.PubMedGoogle Scholar
  57. 57.
    Harvey, P. K. P., Bradford. H. F. & Davison, A. N., 1975. FEBS Lett. 52: 251–254.PubMedGoogle Scholar
  58. 58.
    Whittle, S. R. & Turner, A. J., 1978. J. Neurochem. 31: 1453–1459.PubMedGoogle Scholar
  59. 59.
    Kaufman, E. E., Nelson, T., Goochee, C. & Sokoloff, L., 1979. J. Neurochem. 32: 699–712.PubMedGoogle Scholar
  60. 60.
    Ciesielski, L., Maitre, M., Cash, C. & Mandel, P., 1975. Biochem. Pharmacol. 24: 1055–1058.PubMedGoogle Scholar
  61. 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. 21 1: 583–595.Google Scholar
  62. 62.
    Albertson, T. E., Peterson, S. L., Stark, L. G. & Baselt, R. C., 1981. Neuropharmacol. 20: 95–97.Google Scholar
  63. 63.
    Schechter, P. J., Trainer, Y. & Grove, J., 1978. J. Neurochem. 31: 1325–1327.PubMedGoogle Scholar
  64. 64.
    Perry, T. L. & Hansen, S., 1978. J. Neurochem. 30: 679–684.PubMedGoogle Scholar
  65. 65.
    Kukino, K. & Deguchi, T., 1977. Chem. Pharm. Bull. 25: 2257–2261.PubMedGoogle Scholar
  66. 66.
    Perry, T. L. & Hansen, S., 1973. J. Neurochem. 21: 1167–1175.PubMedGoogle Scholar
  67. 67.
    Perry, T. L., Urquhart, N., Hansen, S. & Kennedy, J., 1974. J. Neurochem. 23: 443 - 445.PubMedGoogle Scholar
  68. 68.
    Perry, T. L., Kish, S. J. & Hansen, S., 1979. J. Neurochem. 32: 1641–1645.PubMedGoogle Scholar
  69. 69.
    Seiler, N., Bink, G. & Grove, J., 1979. Neurochem. Res. 4: 425–435.PubMedGoogle Scholar
  70. 70.
    Seiler, N., Bink, G. & Grove, J., 1980. Neuropharmacol. 19: 251–258.Google Scholar
  71. 71.
    Kuriyama, K., Roberts, E. & Rubinstein, M. K., 1966. Biochem. Pharmacol. 15: 221–236.PubMedGoogle Scholar
  72. 72.
    Wood, J. D. & Peesker, S. J., 1975. J. Neurochem. 25: 277–282.PubMedGoogle Scholar
  73. 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. 74.
    Horton, R. W., Anlezark, G. M., Sawaya, M. C. B. & Meldrum, B. S., 1977.Google Scholar
  75. 75.
    Goldstein, D. B., 1979. J. Pharmacol. Exp. Ther. 208: 223–227.PubMedGoogle Scholar
  76. 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.Google Scholar
  77. 77.
    Stone, W. E., 1977. Epilepsia 18: 507–514.PubMedGoogle Scholar
  78. 78.
    Wood, J. D., Durham, J. S. & Peesker, S. J., 1977. Neurochem. Res. 2: 707–715.Google Scholar
  79. 79.
    Simon, D. & Penry, J. K., 1975. Epilepsia 16: 549–573.PubMedGoogle Scholar
  80. 80.
    Schechter, P. J., Tranier, Y., Jung, M. J., Sjoerdsma, A., 1977. J. Pharmacol. Exp. Ther. 201: 606–612.PubMedGoogle Scholar
  81. 81.
    Schechter, P.J. & Trainer, Y., 1977. Psychopharmacol. 54: 145–148.Google Scholar
  82. 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.Google Scholar
  83. 83.
    Loscher, W., 1980. N.S. Arch. Pharmacol. 315: 119–128.Google Scholar
  84. 84.
    Iadarola, M. J., Raines, A. R. & Gale, K., 1979. J. Neurochem. 33: 1119–1123.PubMedGoogle Scholar
  85. 85.
    Gale, K. & Iadarola, M. J., 1980. Science 208: 288–291.PubMedGoogle Scholar
  86. 86.
    Baxter, C. F. & Roberts, E., 1960. Proc. Soc. Exp. Biol. Med. 104: 426–427.PubMedGoogle Scholar
  87. 87.
    DaVanzo, J. P., Greig, M. E. & Cronin, M. A., 1961. Am. J. Physiol. 201: 833–837.PubMedGoogle Scholar
  88. 88.
    Roa, D. P., Tews, J. K. & Stone, W. E., 1964. Biochem. Pharmacol. 13: 477–487.PubMedGoogle Scholar
  89. 89.
    Murakami, Y., Abe, M. & Murakami, K., 1976. J. Neurochem. 26: 655–656.PubMedGoogle Scholar
  90. 90.
    Maynert, E. W. & Kaji, H. K., 1962. J. Pharmacol. Exp. Ther. 137: 114121.Google Scholar
  91. 91.
    Abe, M. & Matsuda, M., 1977. J. Biochem. 82: 195–200.PubMedGoogle Scholar
  92. 92.
    Wood, J. D., Russell, M. P., Kurylo, E. & Newstead, J. D., 1979. J. Neurochem. 33: 61–68.PubMedGoogle Scholar
  93. 93.
    Wood, J. D., 1975. Prog, in Neurobiol. 5: 77–95.Google Scholar
  94. 94.
    Okada, YU., Nitsch-Hassler, C., Kim, J. S., Bak, I. J. & Hassler, R., 1971. Exp. Brain Res. 14: 514–518.Google Scholar
  95. 95.
    Fahn, S. & Cote, L. J., 1968. J. Neurochem. 15: 209–213.PubMedGoogle Scholar
  96. 96.
    Tappaz, M. L., Brownstein, M. J. & Palkovits, M., 1976. Brain Res. 108: 371–379.PubMedGoogle Scholar
  97. 97.
    Massari, V. J., Gottesfeld, Z. & Jacobowitz, D. M., 1976. Brain Res. 118: 147–151.PubMedGoogle Scholar
  98. 98.
    Tappaz, M. L., Brownstein, M. J. & Kopin, I. J., 1977. Brain Res. 125: 109–121.PubMedGoogle Scholar
  99. 99.
    van der Heyden, J. A. M. & Korf, J., 1979. J. Neurochem. 33: 857–861.PubMedGoogle Scholar
  100. 100.
    Albers, R. W. & Brady, R. O., 1959. J. Biol. Chem. 234: 926–928.PubMedGoogle Scholar
  101. 101.
    Enna, S. J., Kuhar, M. J. & Snyder, S. H., 1975. Brain Res. 43: 168–174.Google Scholar
  102. 102.
    Placheta, P. & Karobath, M., 1979. Brain Res. 178: 580–583.PubMedGoogle Scholar
  103. 103.
    DeFeudis, F. V., 1977. Prog, in Neurobiol. 9: 123–145.Google Scholar
  104. 104.
    Kilpatrick, I. C., Starr, M. S., Fletcher, A., James, T. A. & MacLeod, N. K., 1980. Exp. Brain Res. 40: 45–54.PubMedGoogle Scholar
  105. 105.
    MacLeod, N. K., James, T. A., Kilpatrick, I. C. & Starr, M. S., 1980. Exp. Brain Res. 40: 55–61.PubMedGoogle Scholar
  106. 106.
    Vincent, S. R., Hattori, T. & McGeer, E. G., 1978. Brain Res. 151: 159–164.PubMedGoogle Scholar
  107. 107.
    Hertz, L., 1979. Prog. in Neurobiol. 13: 277–323.Google Scholar
  108. 108.
    Fonnum, F. & Walberg, F., 1973. Brain Res. 54: 115–127.PubMedGoogle Scholar
  109. 109.
    Schon, F. & Kelly, J. S., 1974. Brain Res. 66: 275–288.Google Scholar
  110. 110.
    Iversen, L. L., Dick, F., Kelly, J. S. & Schon, F., 1975. Metabolie Compartmentation and Neurotransmission (Berl, S., Clarke, D. D. & Schneider, D., eds) Plenum Press, new York, pp. 65–89.Google Scholar
  111. 111.
    Hutchinson, H. T., Werrbach, K., Vance, C. & Haber, B., 1974. Brain Res. 66: 265 - 274.Google Scholar
  112. 112.
    Lodge, D., Curtis, D. R. & Johnston, G. A. R., 1978. J. Neurochem. 31: 1525–1528.PubMedGoogle Scholar
  113. 113.
    Yarbrough, G. G., 1978. Can. J. Physiol. Pharmacol. 56: 443–446.PubMedGoogle Scholar
  114. 114.
    Frey, H. H., Popp, C. & Loscher, W., 1979. Neuropharmacol. 18: 581–590.Google Scholar
  115. 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.Google Scholar
  116. 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.Google Scholar
  117. 117.
    Van Gelder, N. M., 1965. J. Neurochem. 12: 231–237.Google Scholar
  118. 118.
    Hyde, J. C. & Robinson, N., 1974. J. Neurochem. 23: 365–367.PubMedGoogle Scholar
  119. 119.
    Schwarcz, R., Bennett, J. P. & Coyle, J. T., 1977. Ann. Neurol. 2: 299–303.PubMedGoogle Scholar
  120. 120.
    Wu, P. H., Durden, D. A. & Hertz, L., 1979. J. Neurochem. 32: 379–390.PubMedGoogle Scholar
  121. 121.
    Kohl, R. L., Quay, W. B. & Perez-Polo, J. R., 1980. J. Neurochem. 34: 1792–1795.PubMedGoogle Scholar
  122. 122.
    Toman, J. E P., Swinyard, E. A. & Goodman, L. S., 1946. J. Neurophysiol. 9: 231–239.PubMedGoogle Scholar
  123. 123.
    Woodbury, L. A. & Davenport, V. D., 1952. Arch. Int. Pharmacodyn. 92: 97–107.PubMedGoogle Scholar
  124. 124.
    Krall, R. L., Penry, J. K., White, B. G., Kupferberg, H. J. & Swinyard, E. A., 1978. Epilepsia 19: 409–428.PubMedGoogle Scholar
  125. 125.
    Coyle, J. T., Molliver, M. E. & Kuhar, M. J., 1978. J. Comp. Neurol. 180: 301–324.PubMedGoogle Scholar
  126. 126.
    Zaczek, R., Schwarcz, R. & Coyle, J. T., 1978. Brain Res. 152: 626–632.PubMedGoogle Scholar
  127. 127.
    Schwarcz, R. & Coyle, J. T., 1977. Brain Res. 127: 235–249.PubMedGoogle Scholar
  128. 128.
    Kim, J. S., Bäk, I. J., Hassler, R. & Okada, Y., 1971. Exp. Bain Res. 14: 95–104.Google Scholar
  129. 129.
    Hattori, T., McGeer, P. L., Fibiger, H. C. & McGeer, E. G., 1973. Brain Res. 54: 103–114.PubMedGoogle Scholar
  130. 130.
    Fonnum, F., Gottesfeld, Z. & Grofova, I., 1978. Brain Res. 143: 125–138.PubMedGoogle Scholar
  131. 131.
    Ribak, C. E., Vaughn, J. E. & Roberts, E., 1980. Brain Res. 192: 413–420.PubMedGoogle Scholar
  132. 132.
    Gale, K. & Iadarola, M. J., 1980. Brain Res. 183: 217–223.PubMedGoogle Scholar
  133. 133.
    Pycock, C. J., 1980. Neurosci. 5: 461–514.Google Scholar
  134. 134.
    Buu, N. T. & Van Gelder, N. M., 1974. Br. J. Pharmacol. 52: 401–406.PubMedGoogle Scholar
  135. 135.
    Knjevic, K. & Schwartz, S., 1968. Structure and Function of Inhibitory Neural Mechanisms (Von Euler, S., Skoglund, S. & Soderberg, U., eds.) Pergamon Press, New York, pp. 419–427.Google Scholar
  136. 136.
    Guidotti, A., Gale, K., Suria, A. & Toffano, G., 1979. Brain Res. 172: 566–571.PubMedGoogle Scholar
  137. 137.
    Waddington, J. L. & Cross, A. J., 1978. Nature 276: 618–620.PubMedGoogle Scholar
  138. 138.
    Iadarola, M. J. & Gale, K., 1979. Eur. J. Pharmacol. 59: 125–129.PubMedGoogle Scholar
  139. 139.
    Beart, P. M., Kelly, J. S. & Schon, F., 1974. Biochem. Soc. Transac. 2: 266–268.Google Scholar
  140. 140.
    Waniewski, R. A. & Suria, A., 1977. Life Sci. 21: 1129–1142.PubMedGoogle Scholar
  141. 141.
    Wood, J. D., Kurylo, E. & Newstead, J. D., 1978. Can. J. Biochem. 56: 667–672.PubMedGoogle Scholar
  142. 142.
    Sarhan, S. & Seiler, N., 1979. J. Neurosci. Res. 4: 398–421.Google Scholar
  143. 143.
    Bell, J. A. & Anderson, E. G., 1974. Neuropharmacol. 13: 885–894.Google Scholar
  144. 144.
    Gottesfeld, Z., Kelly, J. S. & Renaud, L. P., 1972. Brain Res. 11: 319–335.Google Scholar
  145. 145.
    Iadarola, M. J. & Gale, K., 1980. Brain Res. Bull. 5: Suppl. 2, pp. 13–19.Google Scholar
  146. 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.Google Scholar
  147. 147.
    Gale, K. & Iadarola, M. J., 1980. Eur. J. Pharmacol. 68: 233–235.PubMedGoogle Scholar
  148. 148.
    Collins, R. C., McLean, M. & Olney, J., 1980. Life Sci. 27: 855–862.PubMedGoogle Scholar
  149. 149.
    Faeth, W. H., Walker, A. E. & Andy, O. J., 1954. Epilepsia, 3rd Series, 3: 37–48.Google Scholar
  150. 150.
    Casu, M. & Gale, K., 1981. Life Sci., 29: 681–688.PubMedGoogle Scholar
  151. 151.
    Nicklas, W. J., Nunez, R., Berl, S. & Duvoisin, R., 1979. J. Neurochem. 33: 839–844.PubMedGoogle Scholar
  152. 152.
    Casu, M. & Gale, K., 1981. J. Pharmacol. Exp. Ther. 217: 177–180.PubMedGoogle Scholar
  153. 153.
    Casu, M. & Gale, K., 1981. Fed. Proc., 40: 290.Google Scholar

Copyright information

© Martinus Nijhoff/Dr W. Junk Publishers, The Hague 1981

Authors and Affiliations

  • Michael J. Iadarola
    • 1
  • Karen Gale
    • 1
  1. 1.Dept. of PharmacologyGeorgetown University Schools of Medicine and DentistryUSA

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