Summary
Brain tissue levels and in vivo release of substance P (SP) and neurokinin A (NKA) and GABA were measured bilaterally in striatum and substantia nigra of the rat, after a unilateral 6-hydroxydopamine lesion of the nigro-striatal dopamine pathway. Sham injected animals served as controls. The dopamine denervation decreased the tissue levels of SP in striatum (-38%) ipsilateral to the lesion and in substantia nigra both ipsi- (-54%) and contralateral (-38%) to the lesion. NKA was not significantly changed in the striatum, but decreased (like SP) in the substantia nigra both ipsi- (-50%) and contralateral (-40%) to the lesion. GABA tissue levels increased in the denervated striatum (+20%) and remained unchanged in substantia nigra at both sides. The extracellular levels of SP, NKA and GABA were measured with microdialysis in vivo at basal conditions and during stimulation with potassium administered locally via the microdialysis probe. The stimulated release of SP and NKA in the substantia nigra ipsilateral to the lesion was compared to in sham operated animals reduced with 39% and 64%, respectively, while no change in SP or NKA release was detected in the striatum. The basal release of GABA in the striatum was increased with 296% and with 76% during stimulation in the dopamine denervated striatum, while no change in GABA basal or stimulated release was detected in the substantia nigra. We suggest that the increased GABA release in the dopamine denervated striatum may be due to a decreased dopamine mediated inhibition of local GABA neurons. Furthermore, the decreased nigral release of SP and NKA ipsilateral to the lesion is suggested to be caused by an increased GABA inhibition in striatum of SP- and NKA-containing striato-nigral neurons.
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Bannon MJ, Lee J-M, Giraud P, Young A, Affolter H-U, Bonner TI (1986) Dopamine antagonist haloperidol decreases substance P, substance K and preprotachykinin mRNAs in rat striatonigral neurons. J Biol Chem 261: 6640–6642
Bolam JP, Ingham CA, Smith AD (1984) The section-Golgi-impregnation procedure. 3. Combination of Golgi-impregnation with enzyme histochemistry and electron microscopy to characterize acetylcholineesterase-containing neurons in the rat neostriatum. Neuroscience 12: 687–709
Bolam JP, Powell JF, Wu J-Y, Smith AD (1985) Glutamate decarboxylase-immunoreactive structures in the rat neostriatum: a correlated light and electron microscopic study including a combination of golgi impregnation with immunocytochemistry. J Comp Neurol 237: 1–20
Brodin E, Lindefors N, Ungerstedt U (1983) Potassiu-evoked in vivo release of substance P in rat brain using a new technique of brain dialysis and an improved substance P radioimmunoassay. Acta Physiol Scand [Suppl] 515: 17–20
Brodin E, Lindefors N, Dalsgaard C-J, Theodorsson-Norheim E, Rosell S (1986) Tachykinin multiplicity in rat central nervous system as studied using antisera against substance P and neurokinin A. Regul Pept 13: 253–272
Brownstein MJ, Mroz EA, Tappaz ML, Leeman SE (1977) On the origin of substance P and glutamic acid decarboxylase (GAD) in the substantia nigra. Brain Res 135: 315–324
Cheramy A, Nieoullon A, Michelot R, Glowinski J (1977) Effects of intranigral application of dopamine and substance P on the in vivo release of newly synthesized (3H)-dopamine in the ipsilateral caudate nucleus of the cat. Neurosci Lett 4: 105–109
Chesselet M-F (1984) Presynaptic regulation of neurotransmitter release in the brain. Neuroscience 12: 347–375
Collingridge GL, Davies J (1982) Actions of substance P and opiates in the rat substantia nigra. Neuropharmacology 21: 715–719
Gale K, Casu M (1981) Dynamic utilization of GABA in substantia nigra: regulation by dopamine and GABA in the striatum, and its clinical and behavioural implications. Mol Cell Biochem 39: 369–405
Gerfen CR (1984) The neostriatal mosaic: compartmentalization of corticostriatal input and striatonigral output systems. Nature 311: 461–464
Glowinski J, Michelot R, Cheramy A (1980) Role of striato-nigral substance P in the regulation of the activity of the nigrostriatal dopaminergic neurons. In: Costa E, Trabucci M (eds) Neural peptides and neuronal communication. Raven Press, New York, pp 51–62
Grace AA, Bunney BS (1979) Paradoxical GABA excitation of nigral dopaminergic cell: indirect mediation through reticulata inhibitory neurons. Eur J Pharmacol 59: 211–218
Herrera-Marschitz M (1986) Neuropharmacology and functional anatomy of the basal ganglia. Thesis
Hornykiewicz O (1982) Brain neurotransmitter changes in Parkinson's disease. In: Marsden CD, Fahn S (eds) Movement disorders. Butterworth Scientific, London pp 41–58
Innis RB, Andrade R, Aghajanian GK (1985) Substance K excites dopaminergic and non-dopaminergic neurones in rat substantia nigra. Brain Res 335: 381–383
Javoy-Agid F, Ploska A, Agid Y (1981) Microtopography of tyrosine hydroxylase, glutamic acid decarboxylase, and choline acetyl transferase in the substantia nigra and the ventral tegmental area of control and parkinsonian brains. J Neurochem 37: 1218–1227
Jessel TM (1978) Substance P release from the rat substantia nigra. Brain Res 151: 469–478
Jessel TM, Emson PC, Paxinos G, Cuello AC (1978) Topograpahic projections of substance P and GABA pathways in the striato- and pallido-nigral system: a biochemical and immunohistochemical study. Brain Res 152: 487–498
Kimura S, Okada M, Sugita Y, Kanazawa I, Munekata E (1983) Novel neuropeptides, neurokinin alpha and neurokinin beta isolated from porcine spinal cord. Proc Jpn Acad 59B: 101–104
Lee J-M, McLean S, Maggio JE, Zamir N, Roth RH, Eskay RL, Bannon MJ (1986) The localization and characterization of substance P and substance K in striato-nigral neurons. Brain Res 371: 152–154
Lindefors N, Brodin E, Theodorsson-Norheim E, Ungerstedt U (1985a) Regional distribution and in vivo release of tachykinin-like immunoreactivities in rat brain: evidence for regional differences in relative proportions of tachykinins. Regul Pept 10: 217–230
Lindefors N, Brodin E, Theodorsson-Norheim E, Ungerstedt U (1985b) Calcium-dependent potassium-stimulated release of neurokinin A and neurokinin B from rat brain regions in vitro. Neuropeptides 6: 453–461
Lindefors N, Brodin E, Ungerstedt U (1986a) Neuroleptic treatment induces region-specific changes in levels of neurokinin A and substance P in rat brain. Neuropeptides 7: 265–280
Lindefors N, Brodin E, Ungerstedt U (1986b) Neurokinin A and substance P in striato-nigral neurons in rat brain. Neuropeptides 8: 127–132
Lindefors N, Brodin E, Ungerstedt U (1987) Microdialysis combined with a sensitive radioimmunoassay: a technique for studying in vivo release of neuropeptides. J Pharmacol Methods 17: 305–312
Lindroth P, Mopper K (1979) High performance liquid chromatography determination and subpicomole amounts of amino acids by precolumn fluorescence derivatization with o-pthaldialdehyde. Anal Chem 51: 1667–1674
Mauborgne A, Javoy-Agid F, Legrand C, Agid Y, Cesselin F (1983) Decrease of substance P-like immunoreactivity in the substantia nigra and pallidum of parkinsonian brains. Brain Res 268: 167–170
Melis MR, Gale K (1984) Evidence that nigral substance P controls the activity of the nigrotectal GABAergic pathway. Brain Res 295: 389–393
Michelot R, Leviel V, Torrens Y, Glowinski J, Cheramy A (1979) In vivo release of substance P in the cat substantia nigra. Neurosci Lett 15: 141–146
Minamino N, Kanagawa K, Fukuda A, Mabue H (1984) Neuromedin L: a novel mammalian in tachykinin identified in porcine spinal cord. Neuropeptides 4: 157–166
Nagy JI, Vincent SR, Fibiger HC (1978) Altered neurotransmitter synthetic enzyme activity in some extrapyramidal nuclei after lesions of the nigro-striatal dopamine projection. Life Sci 22: 1777–1782
Paxinos S, Watson C (1982) The rat brain atlas in stereotaxic coordinates. Academic Press, Sydney
Perry TL, Javoy-Agid F, Agid Y, Fibiger HC (1983) Striatal GABAergic neuronal activity is not reduced in Parkinson's disease. J Neurochem 40: 1120–1123
Pinnock RD, Dray A (1982) Differential sensitivity of presumed dopaminergic and non-dopaminergic neurons in rat substantia nigra to electrophoretically applied substance P. Neurosci Lett 29: 153–158
Reubi J-C, Iversen LL, Jessel TM (1977) Dopamine selectivity increases 3H-GABA release from slices of rat substantia nigra in vitro. Nature 268: 652–654
Sharp T, Zetterström T, Ungerstedt U (1986) An in vivo study of dopamine release and metabolism in rat brain using intracerebral dialysis. J Neurochem 47: 113–122
Tanaka Y, Niljima K, Mizuno Y, Yoshida M (1986) Changes in gamma-aminobuturate, glutamate, aspartate, glycine and taurine contents in the striatum after unilateral nigrostriatal lesions in rats. Exp Neurol 91: 259–268
Tossman U, Jonsson G, Ungerstedt U (1986a) Regional distribution and extracellular levels of amino acids in rat central nervous system. Acta Physiol Scand 127: 533–545
Tossman U, Segovia J, Ungerstedt U (1986b) Extracellular levels of amaino acids in striatum and globus pallidus of 6-hydroxydopamine lesioned rats measured with microdialysis. Acta Physiol Scand 127: 547–551
Tossman U, Ungerstedt U (1986) Microdialysis in the study of extracellular levels of amino acids in the rat brain. Acta Physiol Scand 128: 9–14
Ungerstedt U (1971) Postsynaptic supersensitivity after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol Scand [Suppl] 367: 69–93
van der Heyden JAM, Venema K, Korf J (1980) Biphasic and opposite effects of dopamine and apomorphine on endogenous GABA release in the rat substantia nigra. J Neurochem 34: 119–125
Waszczak B, Eng N, Walters JR (1980) Effects of muscimol and picrotoxin on single unit activity of substantia nigra neurons. Brain Res 188: 185–197
Young WS III, Bonner TI, Brann MR (1986) Mesencephalic dopamine neurons regulate the expression of neuropeptide mRNAs in the rat forebrain. Proc Natl Acad Sci USA 83: 9827–9831
Zivkovic B, Oblin A, Bartholini G (1985) Progabide reverses the nigral substance P reduction induced by chronic impairement of dopaminergic transmission. Eur J Pharmacol 112: 253–255
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Lindefors, N., Brodin, E., Tossman, U. et al. Tissue levels and in vivo release of tachykinins and GABA in striatum and substantia nigra of rat brain after unilateral striatal dopamine denervation. Exp Brain Res 74, 527–534 (1989). https://doi.org/10.1007/BF00247354
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DOI: https://doi.org/10.1007/BF00247354