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Autoradiographic localization of γ-aminobutyric acidA receptors within the ventral tegmental area

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Abstract

Destruction of intrinsic neurons in the ventral tegmental area (VTA) with the excitotoxin, quinolinic acid produced a significant decrease (80%) in [3H]muscimol binding to GABAA receptors within the parabrachial pigmented and paranigral nuclei of the VTA. Selective destruction of the dopaminergic neurons with 6-hydroxydopamine (6-OHDA) did not reduce [3H]muscimol binding within the VTA. However, the destruction of dopaminergic neurons did produce an increase (20%) in [3H]muscimol binding contralateral to the lesion, suggesting a reduction in the GABAergic innervation to this region. Additionally, destruction of the VTA afferents with quinolinic acid injections in the medial accumbens failed to produce alterations in [3H]muscimol binding within the VTA. These results are consistent with the predominant localization of GABAA receptors to non-dopaminergic neurons intrinsic to the VTA.

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References

  1. Fallon, J. H., and Moore, R. Y. 1978. Catecholamine innervation of the basal forebrain. IV. Topography of the dopamine projection to the basal forebrain and neostriatum. J. Comp. Neurol. 180:545–580.

    Google Scholar 

  2. Beckstead, R. M., Domesick, V. B., and Nauta, W. J. H. 1979. Efferent connections of the substantia nigra and ventral tegmental area in the rat. Brain Res. 175:191–217.

    Google Scholar 

  3. Fallon, J. H., and Loughlin, S. E. 1987. Monoamine innervation of cerebral cortex and a theory of the role of monoamines in cerebral cortex and basal ganglia. Pages 41–127in Jones, E. G. (ed.), Cerebral Cortex, Plenum Press, New York.

    Google Scholar 

  4. Hokfelt, T., Everitt, B. J., Theodorsson-Norheim, E., and Goldstein, M. 1984. Occurrence of neurotensin like immunoreactivity in subpopulations of hypothalamic, mesencephalic and medullary catecholamine neurons. J. Comp. Neurol. 222:543–559.

    Google Scholar 

  5. Seroogy, K. B., Mehta, A., and Fallon, J. H. 1987. Neurotensin and cholecystokinin coexist within neurons of the ventral mesencephalon projections to forebrain. Exp. Br. Res. 68:277–289.

    Google Scholar 

  6. Phillipson, O. T. 1979. Afferent projections to the ventral tegmental area of Tsai and interfascicular nucleus: A horseradish peroxidase study in the rat. J. Comp. Neurol. 187:117–144.

    Google Scholar 

  7. Zahm, D. S. 1989. Evidence for a morphologically distinct subpopulation of striatipetal axons following injections of WGA-HRP into the ventral tegmental area in the rat. Brain Res. 482:145–154.

    Google Scholar 

  8. Fonnum, F., Gottesfeld, Z., and Grofova, I. 1978. Distribution of glutamate decarboxylase, choline acetyltransferase and are matic amino acid decarboxylase in the basal ganglia of normal and operated rats. Evidence for striatopallidal, striatoentopeduncular and striatonigral GABAergic fibres. Brain Res. 143:125–138.

    Google Scholar 

  9. Zahm, D. S., Zaborszky, L., Alones, V. E., and Heimer, L. 1985. Evidence for the xoexistence of glutamate decarboxylase and metenkephalin immunoreactivities in axon terminals of rat ventral pallidum. Brain Res. 325:317–321.

    Google Scholar 

  10. Haber, S. N., and Nauta, W. J. H. 1983. Ramifications of the globus pallidus in the rat as indicated by patterns of immunohistochemistry. Neuroscience 9:245–260.

    Google Scholar 

  11. Paxinos, G., Staines, W. A., Hokfelt, T., Oertel, W. H., and Terenius, L. 1984. Enkephalin (EK), dynorphin (Dyn), Substance P (SP) and glutamic acid decarboxylase (GAD) in striatal efferents. Society for Neuroscience 10:516.

    Google Scholar 

  12. Zaborszky, L., Alheid, G. F., and Heimer, L. 1985. Mapping of transmitter-specific connections: simultaneous demonstration of anterograde degeneration and changes in the immunostaining pattern induced by lesions. J. Neurosci. Methods 14:255–266.

    Google Scholar 

  13. Sugimoto, T., and Mizuno, N. 1987. Neurotensin in projection neurons of the striatum and nucleus accumbens, with reference to coexistence with enkephalin, and GABA: an immunohistochemical study in the cat. J. Comp. Neurol. 257:383–395.

    Google Scholar 

  14. Ribak, C. E., Vaughn, J. E., and Roberts, E. 1980. GABAergic nerve terminals decrease in the substantia nigra following hemitransections of the striatonigral and pallidonigral pathways. Brain Res. 192:413–420.

    Google Scholar 

  15. Nagai, T., McGeer, P. L., and McGeer, E. G. 1983. Distribution of GABA-T intensive neurons in the rat forebrain and midbrain. J. Comp. Neurol. 218:220–238.

    Google Scholar 

  16. Ottersen, O. P., and Storm-Mathisen, J. 1984. Neurons containing or accumulating transmitter amino acids. Pages 141–245in Bjorklund, A., Hokfelt, T., Kuhar, M. J. (eds), Handbook of Chemical Neuroanatomy, Vol. 3, Elsevier Science Publishing, Amsterdam Netherlands.

    Google Scholar 

  17. Bowery, N. G., Hudson, A. L., and Price, G. W., 1987. GABAA and GABAB receptor site distribution in the rat central nervous system. Neuroscience 20:365–383.

    Google Scholar 

  18. Herkenham, M., and Sokoloff, L. 1984. Quantitative receptor autoradiography: tissue defatting eliminates differential self-absorption of tritium radiation in gray and white matter of brain. Brain Res. 321:363–368.

    Google Scholar 

  19. MacNeil, D., Gower, M., and Szymanska, I. 1978. Response of dopamine neurons in substantia nigra to muscimol. Brain Res. 154:401–403.

    Google Scholar 

  20. Walters, J. R., and Lakoski, J. M. 1978. Effect of muscimol on single unit activity of substantia nigra dopamine neurons. Eur. J. Pharmacol. 47:469–471.

    Google Scholar 

  21. Grace, A. A., and Bunney, B. S. 1979. Paradoxical GABA excitation of nigral dopaminergic cells: indirect mediation through reticulata inhibitory neurons. Eur. J. Pharmacol. 59:211–218.

    Google Scholar 

  22. Lacey, M. G., Mercuri, N. B., and North, R. A. 1988. On the potassium conductance increase activated by GABAB and dopamine D2 receptors in rat substantia nigra neurones. J. Physiol. 401:437–453.

    Google Scholar 

  23. Beart, P. M., and McDonald, D. 1980. Neurochemical studies of the mesolimbic dopaminergic pathway. Somatodendritic mechanisms and GABAergic neurones in the rat ventral tegmentum. J. Neurochem. 34:1622–1629.

    Google Scholar 

  24. Kalivas, P. W., Duffy, P., and Eberhardt, H. 1990. Modulation of A10 dopamine neurons by γ-aminobutyric acid agonists. J. Pharmacol. Exp. Ther. 253:858–866.

    Google Scholar 

  25. Palacios, J. M., and Kuhar, M. J. 1981. Neurotensin receptors are located on, dopamine-containing neurones in rat midbrain. Nature 294:587–589.

    Google Scholar 

  26. Quirion, R., Chiueh, C. C., Everist, H. D., and Pert, A. 1985. Comparative localization of neurotensin receptors on nigrostriatal and mesolimbic dopaminergic terminals. Brain Res. 327:385–389.

    Google Scholar 

  27. Dilts, R. P., and Kalivas, P. W. 1989. Autoradiographic localization of μ-opioid and neurotensin receptors within the mesolimbic dopamine system. Brain Res. 488:311–327.

    Google Scholar 

  28. Churchill, L., Dilts, R. P., and Kalivas, P. W. 1990. Changes in γ-aminobutyric acid, μ-opioid and neurotensin receptors in the accumbens-pallidal projection after discrete quinolinic acid lesions in the nucleus accumbens. Brain Res. 511:41–54.

    Google Scholar 

  29. Churchill, L., Bourdelais, A., Austin, M. C., Lolait, S. J., Mahan, L. C., O'Carroll A.-M., and Kalivas, P. W. 1991. GABAA receptors containing α1 and β2 subunits are mainly localized on neurons in the ventral pallidum. Synapse 8:75–85.

    Google Scholar 

  30. Pellegrino, L. J., Pellegrino, A. S., and Cushman, A. J. 1981. A stereotaxic atlas of the rat brain. Plenum Press, New York.

    Google Scholar 

  31. Giralt, M. T., Bonanno, G., and Raiteri, M. 1990. GABA terminal autoreceptors in the pars compacta and in the pars reticulata of the rat substantia nigra are GABAB. Eur. J. Pharmacol. 175:137–144.

    Google Scholar 

  32. Olpe, H. R., Schellenberg, H., and Koella, W. P. 1977. Rotational behavior induced in rats by intranigral application of GABA-related drugs and GABA antagonists Eur. J. Pharmacol. 45:291–298.

    Google Scholar 

  33. Pinnock, R. D. 1984. Hyperpolarizing action of baclofen on neurones in the rat substantia nigra slice. Brain Res. 322:337–340.

    Google Scholar 

  34. Aghjanian, G. K., and Bunney, G. S. 1977. Dopamine “autor-receptors”: Pharmacological characterization by microinotophoretic single unit recording studies. Nauyn Schmiedeberg's Arch. Pharmacol. 297:1–7.

    Google Scholar 

  35. Floran, B., Silva, I., Nava, C., and Aceves, J. 1988. Presynaptic modulation of the release of GABA and GABAA receptors in pars compacta and by GABAB receptors in pars reticulata of the rat substantia nigra. Eur. J. Pharmacol. 150:277–286.

    Google Scholar 

  36. Waddington, J. L., and Cross, A. J. 1978. Denervation supersensitivity in the striatonigral GABA pathway. Nature 276:618–620.

    Google Scholar 

  37. Gale, K. 1980. Chronic blockade of dopamine receptors by antischizophrenic drugs enhances GABA binding in substantia nigra. Nature 283:569–570.

    Google Scholar 

  38. Deutch, A. Y., Kalivas, P. W., Goldstein M., and Roth, R. H. 1986. Interconnections of the mesencephalic dopamine cell groups. Society for Neuroscience 12:875.

    Google Scholar 

  39. Woulfe, J., and Beaudet, A. 1989. Immunocytochemical evidence for direct connections between neurotensin-containing axons and dopaminergic neurons in the rat ventral midbrain tegmentum. Brain Res. 479:402–406.

    Google Scholar 

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Special issue dedicated to Dr. Frederick E. Samson

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Churchill, L., Dilts, R.P. & Kalivas, P.W. Autoradiographic localization of γ-aminobutyric acidA receptors within the ventral tegmental area. Neurochem Res 17, 101–106 (1992). https://doi.org/10.1007/BF00966870

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