Psychopharmacology

, Volume 62, Issue 3, pp 267–277 | Cite as

GABAergic and glycinergic mechanisms within the substantia nigra: Pharmacological specificity of dopamine-independent contralateral turning behavior and interactions with other neurotransmitters

  • Jørn Arnt
  • Jørgen Scheel-Krüger
Original Investigations

Abstract

The pharmacological specificity of the GABA agonist muscimol-induced contralateral turning behavior after unilateral injection into substantia nigra pars reticulata (SNR) has been studied. Muscimol-induced turning was antagonized by intranigral bicuculline methochloride (BMC) and picrotoxin, whereas antagonists of glycine, morphine, dopamine, noradrenaline, and serotonin were ineffective. Glycine induced a qualitatively similar turning behavior which was strychnine-sensitive but relatively BMC and picrotoxin-insensitive. Other drugs, including substance P, kainic acid, clonidine, oxymetazoline, serotonin, and carbachol, induced turning that could be dissociated from the effect of muscimol. Muscimol-induced turning was dopamine-independent, indicated by resistance to haloperidol (1 mg/kg), to pretreatment with reserpine (7.5 mg/kg) plus α-methyl-p-tyrosine (200 mg/kg), to haloperidol injections into the SNR, striatum and nucleus accumbens, and finally to kainic acid lesions of the striatum. 6-Hydroxydopamine lesions increased the efficacy of intranigral muscimol, while kainic acid lesions of the SNR antagonized muscimol. Muscimol-induced turning was inhibited by oxotremorine (0.25 mg/kg), by intranigral carbachol, and by apomorphine (0.1–0.5 mg/kg), but only moderately by intranigrally injected apomorphine. These data suggest specificity of GABA-agonist-induced contralateral turning and indicate an interaction between nigral GABA and other neurotransmitters, particularly dopamine and acetylcholine.

Key words

Muscimol GABA Substantia nigra Turning behavior Glycine Dopamine Apomorphine Noradrenaline Acetylcholine Substance P 

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References

  1. Aghajanian, G. K., Bunney, B. S.: Dopaminergic and non-dopaminergic neurons of substantia nigra: Differential responses to putative transmitters. In: Neuropsychopharmacology, J. R. Boissier, H. Hippius, P. Pichot, eds., pp. 444–452. Amsterdam: Excerpta Medica 1975Google Scholar
  2. Andén, N. E., Stock, G.: Inhibitory effect of gammahydroxybutyric acid and gammaaminobutyric acid on the dopamine cells in substantia nigra. Naunyn-Schmiedebergs Arch. Pharmacol. 279, 89–92 (1973)Google Scholar
  3. Arnt, J., Scheel-Krüger, J., Magelund, G., Krogsgaard-Larsen, P., Hjeds, H.: Muscimol analogues injected into the substantia nigra: A valuable new in vivo model for GABAergic drugs. In: Amino acids as chemical transmitters, F. Fonnum, ed., pp. 323–326. New York: Plenum 1978Google Scholar
  4. Arnt, J., Scheel-Krüger, J., Magelund, G., Krogsgaard-Larsen, P.: Muscimol and related GABA agonists: The potency of GABAergic drugs in vivo determined after intranigral injection. J. Pharm. Pharmacol. (in press, 1979)Google Scholar
  5. Bache, S., Møller-Nielsen, I.: Turning behavior in rats after intranigral injection of GABA agonists and antagonists and opiate agonists and antagonists. Abstract 1543, Seventh Int. Congress of Pharmacology, Paris (1978)Google Scholar
  6. Berthelsen, S., Pettinger W. A.: A functional basis for classification of α-adrenergic receptors. Life Sci. 21, 595–606 (1977)Google Scholar
  7. Broekkamp, C., van Rossum, J. M.: Clonidine induced hypothalamic stimulation of eating in rats. Psychopharmacologia (Berl.) 25, 162–168 (1972)Google Scholar
  8. Brownstein, M. J., Mroz, E. A., Tappaz, M. L., Leeman, S. E.: On the origin of substance P and glutamic acid decarboxylase (GAD) in substantia nigra. Brain Res. 135, 315–323 (1977)Google Scholar
  9. Chéramy, A., Nieoullon, A., Glowinski, J.: GABAergic processes involved in the control of dopamine release from nigrostriatal dopaminergic neurones in the cat. Eur. J. Pharmacol. 48, 281–295 (1978a)Google Scholar
  10. Chéramy, A., Nieoullon, A., Glowinski, J.: Inhibition of dopamine release in the cat caudate nucleus by nigral application of glycine. Eur. J. Pharmacol. 47, 141–147 (1978b)Google Scholar
  11. Coyle, J. T., Schwarcz, R., Bennett, J. P., Campochiaro, P.: Clinical, neuropathologic and pharmacologic aspects of Huntington's disease: Correlates with a new animal model. Prog. Neuro-Psychopharmacol. 1, 13–30 (1977)Google Scholar
  12. Davies, J., Dray, A.: Substance P in the substantia nigria. Brain Res. 107, 623–627 (1976)Google Scholar
  13. De Montis, G. M., Olianas, M. C., Serra, G., Tagliamonte, A., Scheel-Krüger, J.: Evidence that a nigra 1GABAergic-cholinergic balance controls posture. Eur. J. Pharmacol. 53, 181–190 (1979)Google Scholar
  14. De Montis, G. M., Olianas, M. C., Rawlow, A., Tagliamonte, A., Scheel-Krüger, J.: GABA receptor binding in the substantia nigra following local injection of kainic acid or 6-OHDA. Eur. J. Pharmacol., submitted publication (1978b)Google Scholar
  15. Di Chiara, G., Olianas, M., Del Fiacco, M., Spano, P. F., Tagliamonte, A.: Intranigral kainic acid is evidence that nigral nondopaminergic neurones control posture. Nature 268, 743–745 (1977)Google Scholar
  16. Dray, A., Straughan, D. W.: Synaptic mechanisms in the substantia nigra. J. Pharm. Pharmacol. 28, 400–405 (1976)Google Scholar
  17. Dray, A., Gonye, T. J., Oakley, N. R.: Caudate stimulation and substantia nigra activity in the rat. J. Physiol. (Lond.) 259, 825–849 (1976)Google Scholar
  18. Dray, A., Fowler, L. J., Oakley, N. R., Simmonds, M. A., Tanner, T.: Regulation of nigro-striatal dopaminergic neurotransmission in the rat. Neuropharmacology 16, 511–518 (1977)Google Scholar
  19. Fonnum, F., Grofova, I., Rinvik, E., Storm-Mathiesen, J., Walberg, F.: Origin and distribution of glutamate decarboxylase in substantia nigra of the cat. Brain Res. 71, 77–92 (1974)Google Scholar
  20. Fonnum, F., Gottesfeld, Z., Grofova, I.: Distribution of glutamate decarboxylase, choline acetyltransferase and aromatic amino acid decarboxylase in the basal ganglia of normal and operated rats. Evidence for striatopallidal, striatoentopeduncular and striatonigral GABAergic fibers. Brain Res. 143, 125–138 (1978)Google Scholar
  21. Garcia-Munoz, M., Nicolaou, N. M., Tulloch, I. F., Wright, A. K., Arbuthnott, G. W.: Feedback loop or output pathway in striatonigral fibers? Nature 265, 363–365 (1977)Google Scholar
  22. Glick, S. D., Jerussi, T. P., Fleisher, L. N.: Turning in circles: The neuropharmacology of rotation. Life Sci. 18, 889–896 (1976)Google Scholar
  23. Hill, R. G., Simmonds, M. A., Straughan, D. W.: Antagonism of γ-aminobutyric acid and glycine by convulsants in the cuneate nucleus of cat. Br. J. Pharmacol. 56, 9–19 (1976)Google Scholar
  24. Iwamoto, E. T., Way, E. L.: Circling behavior and stereotypy induced by intranigral opiate microinjections. J. Pharmacol. Exp. Ther. 203, 347–359 (1977)Google Scholar
  25. James, T. A., Starr, M. S.: Behavioral and biochemical effects of substance P injected into the substantia nigra of the rat. J. Pharm. Pharmacol. 29, 181–182 (1977)Google Scholar
  26. Johnston, G. A. R.: Neuropharmacology of amino acid inhibitory transmitters. Annu. Rev. Pharmacol. Toxicol. 18, 269–289 (1978)Google Scholar
  27. Johnston, G. A. R., Kennedy, S. M. E., Lodge, D.: Muscimol uptake, release and binding in rat brain slices. J. Neurochem. 31, 1519–1523 (1978)Google Scholar
  28. Kelly, P. H., Moore, K. E.: Mesolimbic dopamine neurons: Effects of 6-hydroxydopamine induced destruction and receptor blockade on drug-induced rotation of rats. Psychopharmacology 55, 35–41 (1977)Google Scholar
  29. König, J. F. R., Klippel, R. A.: The rat brain: A stereotaxic atlas of the forebrain and lower parts of the brain stem. Baltimore: Williams and Wilkins 1963Google Scholar
  30. Lloyd, K. G., Möhler, H., Heitz, P. H., Bartholini, G.: Distribution of choline acetyltransferase and glutamate decarboxylase within the substantia nigra and in other brain regions from control and parkinsonian patients. J. Neurochem. 25, 789–795 (1975)Google Scholar
  31. McGeer, P. L., McGeer, E. G.: Enzymes associated with the metabolism of catecholamines, acetylcholine and GABA in human controls and patients with Parkinson's disease and Huntington's chorea. J. Neurochem. 26, 65–76 (1976)Google Scholar
  32. McGeer, E. G., Innanen, V. T., McGeer, P. L.: Evidence on the cellular localization of adenyl cyclase in the neostriatum. Brain Res. 118, 356–358 (1976)Google Scholar
  33. McG Donaldson, I., Dolphin, A., Jenner, P., Marsden, C. D., Pycock, C. J.: The roles of noradrenaline and dopamine in contralateral circling behavior seen after unilateral electrolytic lesions of the locus coeruleus. Eur. J. Pharmacol. 39, 179–191 (1976)Google Scholar
  34. Mendez, J. S., Finn, B. W., Dahl, K. E.: Rotatory behavior induced by glycine injected into the substantia nigra of the rat. Exp. Neurol. 50, 174–179 (1976)Google Scholar
  35. Oberlander, C., Dumont, C., Boissier, J. R.: Rotational behavior after unilateral intranigral injection of muscimol in rats. Eur. J. Pharmacol. 43, 389–390 (1977)Google Scholar
  36. Olianas, M. C., De Montis, G. M., Mulas, G., Tagliamonte, A.: The striatal dopaminergic functions is mediated by the inhibition of a nigral, nondopaminergic neuronal system via a strio-nigral GABAergic pathway. Eur. J. Pharmacol. 49, 233–241 (1978a)Google Scholar
  37. Olianas, M. C., De Montis, G. M., Concu, A. A., Tagliamonte, A., Di Chiara, G.: Intranigral kainic acid: Evidence for nigral nondopaminergic neurons controlling posture and behavior in a manner opposite to the dopaminergic ones. Eur. J. Pharmacol. 49, 223–232 (1978b)Google Scholar
  38. Olpe, H. R., Koella, W. P.: Rotatory behavior in rats by intranigral application of substance P and an eledoisin fragment. Brain Res. 126, 576–579 (1977)Google Scholar
  39. Olpe, H. R., Schellenberg, H., Koella, W. P.: Rotational behavior induced in rats by intranigral application of GABA-related drugs and GABA-antagonists. Eur. J. Pharmacol. 45, 291–294 (1977)Google Scholar
  40. Perry, T. L., Berry, K., Hansen, S., Diamond, S., Mok, C.: Regional distribution of amino acids in human brain obtained at autopsy. J. Neurochem. 18, 513–519 (1971)Google Scholar
  41. Philipson, O. T., Emson, P. C., Horn, A. S., Jessell, T.: Evidence concerning the anatomical location of the dopamine stimulated adenylate cyclase in the substantia nigra. Brain Res. 136, 45–58 (1977)Google Scholar
  42. Pycock, C. J., Marsden, C. D.: The rotating rodent: A two component system? Eur. J. Pharmacol. 47, 167–175 (1978)Google Scholar
  43. Racagni, G., Bruno, F., Cattabeni, F., Maggi, A., Di Guilio, A. M., Parenti, M., Groppetti, A.: Functional interaction between rat substantia nigra and striatum: GABA and dopamine interrelation. Brain Res. 134, 353–358 (1977)Google Scholar
  44. Reubi, J. C., Iversen, L. L., Jessell, T. M.: Dopamine selectively increases 3H-GABA release from slices of rat substantia nigra in vitro. Nature 268, 652–654 (1977)Google Scholar
  45. Scheel-Krüger, J., Arnt, J., Magelund, G.: Behavioral stimulation induced by muscimol and other GABA agonists injected into the substantia nigra. Neurosci. Letters 4, 351–356 (1977)Google Scholar
  46. Scheel-Krüger, J., Arnt, J., Bræstrup, C., Christensen, A. V., Magelund, G.: Development of new animal models for GABAergic actions using muscimol as a tool. In: GABA-neurotransmitters, P. Krogsgaard-Larsen, J. Scheel-Krüger, H. Kofod, eds., pp. 447–464. Copenhagen: Munksgaard, New York: Academic Press 1979Google Scholar
  47. Schwarcz, R., Coyle, J. T.: Striatal lesions with kainic acid: Neurochemical characteristics. Brain Res. 127, 235–249 (1977)Google Scholar
  48. Siegel, S.: Non-parametric statistics for the behavioral sciences. New York: McGraw-Hill 1956Google Scholar
  49. Spano, P. F., Trabucchi, M., Di Chiara, G.: Localization of nigral dopamine-sensitive adenylate cyclase on neurons originating from corpus striatum. Science 196, 1343–1345 (1977)Google Scholar
  50. Tarsy, D., Pycock, C., Meldrum, B. S., Marsden, C. D.: Rotational behavior induced in rats by intranigral picrotoxin. Brain Res. 89, 160–165 (1975)Google Scholar
  51. Tuomisto, L., Tuomisto, J., Smissman, E.: Dopamine uptake in striatal and hypothalamic synaptosomes: Conformational selectivity of the inhibition. Eur. J. Pharmacol. 25, 351–361 (1974)Google Scholar
  52. Wolfarth, S., Dulska, E., Golembiowska-Nikitin, K., Vetulani, J.: A role of the polysynaptic system of substantia nigra in the cholinergic-dopaminergic equilibrium in the central nervous system. Naunyn-Schmiedebergs Arch. Pharmacol. 302, 123–131 (1978)Google Scholar

Copyright information

© Springer-Verlag 1979

Authors and Affiliations

  • Jørn Arnt
    • 1
  • Jørgen Scheel-Krüger
    • 2
  1. 1.Department of PharmacologyRoyal Danish School of PharmacyCopenhagen ØDenmark
  2. 2.Psychopharmacological Research Laboratory, Department ESct. Hans Mental HospitalRoskildeDenmark

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