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

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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.

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References

  • 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 1975

    Google Scholar 

  • 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 

  • 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 1978

    Google Scholar 

  • 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)

  • 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)

  • Berthelsen, S., Pettinger W. A.: A functional basis for classification of α-adrenergic receptors. Life Sci. 21, 595–606 (1977)

    Google Scholar 

  • Broekkamp, C., van Rossum, J. M.: Clonidine induced hypothalamic stimulation of eating in rats. Psychopharmacologia (Berl.) 25, 162–168 (1972)

    Google Scholar 

  • 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 

  • 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 

  • 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 

  • 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 

  • Davies, J., Dray, A.: Substance P in the substantia nigria. Brain Res. 107, 623–627 (1976)

    Google Scholar 

  • 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 

  • 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)

  • 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 

  • Dray, A., Straughan, D. W.: Synaptic mechanisms in the substantia nigra. J. Pharm. Pharmacol. 28, 400–405 (1976)

    Google Scholar 

  • 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 

  • 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 

  • 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 

  • 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 

  • 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 

  • Glick, S. D., Jerussi, T. P., Fleisher, L. N.: Turning in circles: The neuropharmacology of rotation. Life Sci. 18, 889–896 (1976)

    Google Scholar 

  • 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 

  • 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 

  • 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 

  • Johnston, G. A. R.: Neuropharmacology of amino acid inhibitory transmitters. Annu. Rev. Pharmacol. Toxicol. 18, 269–289 (1978)

    Google Scholar 

  • 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 

  • 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 

  • 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 1963

    Google Scholar 

  • 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 

  • 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 

  • 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 

  • 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 

  • 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 

  • 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 

  • 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 

  • 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 

  • 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 

  • 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 

  • 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 

  • 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 

  • Pycock, C. J., Marsden, C. D.: The rotating rodent: A two component system? Eur. J. Pharmacol. 47, 167–175 (1978)

    Google Scholar 

  • 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 

  • 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 

  • 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 

  • 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 1979

    Google Scholar 

  • Schwarcz, R., Coyle, J. T.: Striatal lesions with kainic acid: Neurochemical characteristics. Brain Res. 127, 235–249 (1977)

    Google Scholar 

  • Siegel, S.: Non-parametric statistics for the behavioral sciences. New York: McGraw-Hill 1956

    Google Scholar 

  • 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 

  • 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 

  • 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 

  • 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 

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Authors and Affiliations

  1. Department of Pharmacology, Royal Danish School of Pharmacy, 2 Universitetsparken, DK-2100, Copenhagen Ø, Denmark

    Jørn Arnt

  2. Psychopharmacological Research Laboratory, Department E, Sct. Hans Mental Hospital, Roskilde, Denmark

    Jørgen Scheel-Krüger

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  1. Jørn Arnt
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Arnt, J., Scheel-Krüger, J. GABAergic and glycinergic mechanisms within the substantia nigra: Pharmacological specificity of dopamine-independent contralateral turning behavior and interactions with other neurotransmitters. Psychopharmacology 62, 267–277 (1979). https://doi.org/10.1007/BF00431958

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