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Antiparkinsonian actions of glutamate antagonists — alone and with L-DOPA: A review of evidence and suggestions for possible mechanisms

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Journal of Neural Transmission - Parkinson's Disease and Dementia Section

Summary

There has been much speculation of late as to whether antagonists of glutamate receptors can be used to combat the motor difficulties of Parkinson's disease, either as monotherapy, or as polytherapy to boost the effects of conventional L-DOPA treatment. The latter seems to be the more practical approach and the therapeutic implications of such treatment have been discussed in some detail. However, the mechanisms by which glutamate antagonists potentiate the antiparkinsonian actions of L-DOPA, remain cryptic. In this review we have explored the evidence and considered the practicality of using NMDA and non-NMDA receptor blockers to treat parkinsonism, as well as focusing on the ways in which the behavioural synergy between dopamine and glutamate systems could conceivably arise at the cellular level. Particular attention has been paid to the differential interaction between glutamate antagonists and postsynaptic dopamine D1 and D2 receptory mechanisms, since these are currently believed to reflect the activity of the two major basal ganglia output circuits: the so-calleddirect pathway to the substantia nigra and theindirect pathway to the globus pallidus. Finally, we have considered the new proposal, that inhibiting glutamate transmission in the basal ganglia accelerates the enzymic conversion of L-DOPA to dopamine at presynaptic sites.

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References

  • Anderson JJ, Chase TN, Engber TM (1992) Differential effect of subthalamic nucleus ablation on dopamine D1 and D2 agonist-induced rotation in 6-hydroxydopaminelesioned rats. Brain Res 588: 307–310

    Google Scholar 

  • Ary TE, Komiskey HL (1982) Phencyclidine-induced release of [3H]dopamine from chopped striatal tissue. Neuropharmacology 21: 639–645

    Google Scholar 

  • Barbeito I, Girault JA, Godeheu G, Pittaluga A, Glowinski J, Chéramy A (1989) Activation of the bilateral corticostriatal glutamatergic projection by infusion of GABA into thalamic motor nuclei in the cat: an in vivo release study. Neuroscience 28: 365–374

    Google Scholar 

  • Beaton JA, Stemsrud K, Monaghan DT (1992) Identification of a novel N-methyl-D-aspartate receptor population in the rat medial thalamus. J Neurochem 59: 754–757

    Google Scholar 

  • Berger B, Febvret A, Greengard P, Goldman-Rakic PS (1990) DARPP-32, a phosphoprotein enriched in dopaminoceptive neurons bearing dopamine D1 receptors: distribution in the cerebral cortex of the newborn and adult rhesus monkey. J Comp Neurol 299: 327–348

    Google Scholar 

  • Bergman H, Wichmann T, DeLong MR (1990) Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science 249: 1436–1438

    Google Scholar 

  • Berretta S, Roberston HA, Graybiel AM (1992) Dopamine and glutamate agonists stimulate neuron-specific expression of Fos-like protein in the striatum. J Neurophysiol 68: 767–777

    Google Scholar 

  • Biggs CS, Fowler LJ, Whitton PS, Starr MS (1995) N-methyl-D-aspartate receptor antagonists increase the release of dopamine newly synthesised from L-3,4-dihydroxyphenylalanine in the substantia nigra of reserpine-treated rats. Eur J Pharmacol (in press)

  • Boldry RC, Chase TN, Engber TM (1993) Influence of previous exposure to levodopa on the interaction between dizocilpine and dopamine D1 and D2 agonist in rats with 6-hydroxydopamine-induced lesions. J Pharmacol Exp Ther 267: 1454–1459

    Google Scholar 

  • Brené S, Herrera-Marschitz M, Persson H, Lindefors N (1994) Expression of mRNAs encoding dopamine receptors in striatal regions is differentially regulated by midbrain and hippocampal neurons. Mol Brain Res 21: 274–282

    Google Scholar 

  • Brotchie JM, Mitchell IJ, Sambrook MA, Crossman AR (1991) Alleviation of parkinsonism by antagonism of excitatory amino acid transmission in the medial segment of the globus pallidus in rat and primate. Mov Disord 6: 133–138

    Google Scholar 

  • Brown LL, Makman MH, Wolfson LI, Dvorkin B, Warner C, Katzman R (1979) A direct role of dopamine in the rat subthalamic nucleus and an adjacent intrapeduncular area. Science 206: 1416–1418

    Google Scholar 

  • Bubser M, Keseberg U, Notz PK, Schmidt WJ (1992) Differential behavioural and neurochemical effects of competitive and non-competitive NMDA receptor antagonists in rats. Eur J Pharmacol 229: 75–82

    Google Scholar 

  • Calabresi P, Mercuri NB, Sancesario G, Bernardi G (1993) Electrophysiology of dopamine-denervated striatal neurons. Implications for Parkinson's disease. Brain 116: 433–452

    Google Scholar 

  • Campbell GA, Eckhardt MJ, Weight FF (1985) Dopaminergic mechanisms in subthalamic nucleus of rat: analysis using horseradish peroxidase and microiontophoresis. Brain Res 333: 261–270

    Google Scholar 

  • Carlson JH, Bergstrom DA, Demo SD, Walters JR (1990) Nigrostriatal lesion alters neurophysiological responses to selective and nonselective D-1 and D-2 dopamine agonists in rat globus pallidus. Synapse 5: 83–93

    Google Scholar 

  • Carlsson ML (1993) Are the disparate pharmacological profiles of competitive and uncompetitive NMDA antagonists due to different baseline activities of distinct glutamatergic pathways? J Neural Transm [Gen Sect] 75: 221–226

    Google Scholar 

  • Carlsson M, Carlsson A (1989a) The NMDA antagonist MK-801 causes marked locomotor stimulation in monoamine-depleted mice. J Neural Transm [Gen Sect] 75: 221–226

    Google Scholar 

  • Carlsson M, Carlsson A (1989b) Dramatic synergism between MK-801 clonidine with respect to locomotor stimulatory effect in monoamine-depleted mice. J Neural Transm [Gen Sect] 77: 65–71

    Google Scholar 

  • Carlsson M, Carlsson A (1990) Interactions between glutamatergic and monoaminergic systems within the basal ganglia — implications for schizophrenia and Parkinson's disease. Trends Neurosci 13: 272–276

    Google Scholar 

  • Carlsson M, Svensson A, Carlsson A (1991) Synergistic interactions between muscarinic antagonists, adrenergic agonists and NMDA antagonists with respect to locomotor stimulatory effects in monoamine-depleted mice. Naunyn Schmiedebergs Arch Pharmacol 343: 568–573

    Google Scholar 

  • carroll CB, Holloway V, Brotchie JM, Mitchell IJ (1995) Neurochemical and behavioural investigations of the NMDA receptor-associated glycine site in the rat striatum: functional implications for treatment of parkinsonian symptoms. Psychopharmacology 119: 55–65

    Google Scholar 

  • Carter A (1994) Many agents that antagonize the NMDA receptor-channel complex in vivo also cause disturbances of motor coordination. J Pharmacol Exp Ther 269: 573–580

    Google Scholar 

  • Castel M-N, Morino P, Nylander I, Terenius L, Hökfelt T (1994) Differential dopaminergic regulation of the neurotensin striatonigral and striatopallidal pathways in the rat. Eur J Pharmacol 262: 1–10

    Google Scholar 

  • Clineschmidt BV, Martin GE, Bunting PR, Papp NL (1982) Central sympathomimetic activity of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), a substance with potent anticonvulsant, central sympathomimetic, and apparent anxiolytic properties. Drug Dev Res 2: 135–145

    Google Scholar 

  • Close SP, Elliott PJ, Hayes AG, Marriott AS (1990) Effects of classical and novel agents in a MPTP-induced reversible model of Parkinson's disease. Psychopharmacology 102: 295–300

    Google Scholar 

  • Consolo S, Girotti P, Russi G, Di Chiara G (1992) Endogenous dopamine facilitates striatal in vivo acetylcholine release by acting on D1 receptors localized in the striatum. J Neurochem 59: 1555–1557

    Google Scholar 

  • Costall B, Naylor RJ (1975) Neuropharmacological studies on D 145 (1,3-dimethyl-5-aminoadamantan). Psychopharmacologia 43: 53–61

    Google Scholar 

  • Criswell HE, Johnson KB, Mueller RA, Breese GR (1993) Evidence for involvement of brain dopamine and other mechanisms in the behavioral action of the N-methyl-D-aspartic acid antagonist Mk-801 in control and 6-hydroxydopamine-lesioned rats. J Pharmacol Exp Ther 265: 1001–1010

    Google Scholar 

  • Crossman AR, Peggs D, Boyce S, Luquin MR, Sambrook MA (1989) Effect of the NMDA antagonist MK-801 on MPTP-induced parkinsonism in the monkey. Neuropharmacology 28: 1271–1273

    Google Scholar 

  • Dall'Olio R, Facchinetti F, Contestabile A, Gandolfi O (1994) Chronic neonatal blockade of N-methyl-D-aspartate receptor by CGP 39551 increases dopaminergic function in adult rat. Neuroscience 63: 451–455

    Google Scholar 

  • Damsma G, Robertson GS, Tham C-S, Fibiger HC (1991) Dopaminergic regulation of striatal acetylcholine release: importance of D1 and N-methyl-D-aspartate receptors. J Pharmacol Exp Ther 259: 1064–1072

    Google Scholar 

  • Danysz W, Gossel M, Zajaczkowski W, Dill D, Quack G (1994) Are NMDA antagonistic properties relevant for antiparkinsonian-like activity in rats? — Case of amantadine and memantine. J Neural Transm [P-D Sect] 7: 155–166

    Google Scholar 

  • Diana G, Sagratella S (1994) Different capability of N-methyl-D-aspartate antagonists to affect locomotor/exploratory activity of mice in a computerized on-line open field test. Pharmacol Biochem Behav 48: 291–295

    Google Scholar 

  • Di Chiara G, Morelli M, Consolo S (1994) Modulatory functions of neurotransmitters in the striatum: Ach/dopamine/NMDA interactions. Trends Neurosci 17: 288–233

    Google Scholar 

  • Difazio MC, Hollingsworth Z, Young AB, Penney JB (1992) Glutamate receptors in the substantia nigra of Parkinson's disease brains. Neurology 42: 402–406

    Google Scholar 

  • Domino EF, Sheng J (1993) N-methyl-D-aspartate receptor antagonist abd dopamine D1 and D2 agonist interactions in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridiine-induced hemiparkinsonian monkeys. J Pharmacol Exp Ther 264: 221–225

    Google Scholar 

  • Dragunow M, Robertson GS, Faull RLM, Robertson HA, Jansen K (1990) D2 dopamine receptor antagonists induced Fos and related proteins in rat striatal neurons. Neuroscience 37: 287–294

    Google Scholar 

  • Engber TM, Anderson JJ, Boldry RC, Kuo S, Chase TN (1993) N-methyl-D-aspartate receptor blockade differentially modifies regional cerebral metabolic responses to D1 and D2 dopamine agonists in rats with a unilateral 6-hydroxydopamine lesion. Neuroscience 54: 1051–1061

    Google Scholar 

  • Engber TM, Anderson JJ, Boldry RC, Papa SM, Kuo S, Chase TN (1994) Excitatory amino acid receptor antagonists modify regional cerebral metabolic responses to levodopa in 6-hydroxydopamine-lesioned rats. Neuroscience 59: 389–399

    Google Scholar 

  • Ferré S, Giménez-Llort L, Artigas F, Martinez E (1994) Motor activation in short- and long-term reserpinized mice: role of N-methyl-D-aspartate, dopamine D1 and dopamine D2 receptors. Eur J Pharmacol 255: 203–213

    Google Scholar 

  • Filion M, Tremblay L (1991) Abnormal spontaneous activity of globus pallidus neurons in monkeys with MPTP-induced parkinsonism. Brain Res 547: 142–151

    Google Scholar 

  • Filion, M, Tremblay L, Bédard PJ (1991) Effects of dopamine agonists on the spontaneous activity of globus pallidus neurons in monkeys with MPTP-induced parkinsonism. Brain Res 547: 152–161

    Google Scholar 

  • Fletcher GH, Starr MS (1987) Behavioural evidence for the functionality of D-2 but not D-1 dopamine receptors at multiple sites in the 6-hydroxydopamine-lesioned rat. Eur J Pharmacol 138: 407–411

    Google Scholar 

  • Flores G, Valencia J, Sierra A, Rosales M, Hernandez J, Aceves J (1992) Dopaminergic input to the subthalamic nucleus regulates the muscular tone in the rat. Soc Neurosci Abstr 18: 894

    Google Scholar 

  • Fredriksson A, Gentsch C, Archer T (1994) Synergistic interactions between NMDA-antagonists and L-Dopa on activity in MPTP-treated mice. J Neural Transm [Gen Sect] 97: 197–209

    Google Scholar 

  • Gerfen Cr, Engber TM, Mahan CL, Susel Z, Chase TN, Monsma FJ, Sibley DR (1990) D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopalldial neurons. Science 250: 1429–1432

    Google Scholar 

  • Gianutsos G, Chute S, Dunn JP (1985) Pharmacological changes in dopaminergic systems induced by long-term administration of amantadine. Eur J Pharmacol 110: 357–361

    Google Scholar 

  • Giovannini MG, Camilli F, Mundula A, Bianchi L, Colivicchi MA, Pepeu G (1995) Differential regulation by N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors of acetylcholine release from the rat striatum in vivo. Neuroscience 65: 409–415

    Google Scholar 

  • Goodwin P, Starr BS, Starr MS (1992) Motor responses to dopamine D1 and D2 agonists in the reserpine-treated mouse are affected differentially by the NMDA receptor antagonist MK 801. J Neural Transm [PD-Sect] 4: 14–26

    Google Scholar 

  • Graham WC, Robertson RG, Sambrook MA, Crossman AR (1990) Injection of excitatory amino acid antagonists into the medial pallidal segment of 1-methy1-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP) treated primate reverses motor symptoms of parkinsonism. Life Sci 47: PL91-PL97

    Google Scholar 

  • Greemamyre JT, O'Brien CF (1991) N-methyl-D-aspartate antagonists in the treatment of parkinsonismdisease. Arch Neurol 48: 977–981

    Google Scholar 

  • Hadjiconstantinou M, Wemlinger TA, Sylvia CP, Hubble JP, Neff NH (1993) Aromatic L-amino acid decarboxylase activity of mouse striatum is modulated via dopamine receptors. J Neurochem 60: 2175–2180

    Google Scholar 

  • Halpain S, Girault JA, Greengard P (1990) Activation of NMDA receptors induces dephosphorylation of DARPP-32 in rat striatal slices. Nature 343: 369–372

    Google Scholar 

  • Hetzler BE, Waultlet BS (1985) Ketamine-induced locomotion in rats in an open-field. Pharmacol Biochem Behav 22: 653–655

    Google Scholar 

  • Hu X-T, Wachtel SR, Galloway MP, White FJ (1990) Lesions of the nigrostriatal dopamine projection increase the inhibitory effects of D1 and D2 dopamine agonists on caudate-putamen neurons and relieve D2 receptors from the necessity of D1 receptor stimulation. J Neurosci 10: 2318–2329

    Google Scholar 

  • Izenwasser S, Katz JL (1993) Differential efficacies of dopamine D1 receptor agonists for stimulating adenylyl cyclase in squirrel monkey and rat. Eur J Pharmacol [Mol Pharmacol Sect] 246: 39–44

    Google Scholar 

  • Kaddis FG, Wallace LJ, Uretsky NJ (1993) AMPA/kainate antagonists in the nucleus accumbens inhibit locomotor stimulatory response to cocaine and dopamine agonists. Pharmacol Biochem Behav 46: 703–708

    Google Scholar 

  • Kannari K, Markstein R (1991) Dopamine agoniste potentiate antiakinetic effects of competitive NMDA-antagonists in monoamine-depleted mice. J Neural Transm [Gen Sect] 84: 211–220

    Google Scholar 

  • Kaur S, Starr MS (1995a) Antiparkinsonian action of dextromethorphan in the reserpine-treated mouse. Eur J Pharmacol (in press)

  • Kaur S, Starr MS (1995b) Interactions between NMDA open channel blockers and dopamine behaviours in the reserpine-treated mouse: a comparative study. Eur J Pharmacol 280: 159–166

    Google Scholar 

  • Kaur S, Starr MS (1995c) Antiakinetic responses to excitatory amino acid antagonists injected into the striatum and nigra of reserpine-treated rats. Eur J Pharmacol (in press)

  • Kaur S, Starr MS, Starr BS (1994) Role of D1 receptor mechanisms in the potentiation of motor responses to L-DOPA and apomorphine by MK 801 in the reserpine-treated mouse. J Neural Transm [PD-Sect] 7: 133–142

    Google Scholar 

  • Kitai ST, Surmeier DJ (1993) Cholinergic and dopaminergic modulation of potassium conductances in neostriatal neurons. Adv Neurol 60: 40–52

    Google Scholar 

  • Klockgether T, Turski L (1990) NMDA antagonists potentiate antiparkinsonian actions of L-dopa in monoamine-depleted rats. Ann Neurol 28: 539–546

    Google Scholar 

  • Klockgether T, Turski L, Schwarz M, Sontag K-H (1986) Motor actions of excitatory amino acids and their antagonists within the rat ventromedial thalamic nucleus. Brain Res 399: 1–9

    Google Scholar 

  • Klockgether T, Turski L, Honoré T, Zhang Z,Gash DM, Kurlan R, Greenamyre JT (1991) The AMPA receptor antagonist NBQX has antiparkinsonian effects in monoamine depleted rats and MPTP treated monkeys. Ann Neurol 30: 717–723

    Google Scholar 

  • Komori K, Uesaka S, Yamaoka H, Fujita K, Yamaoka K, Naitoh H, Kuroda M, Karasawa N, Ito T, Kasahara Y, Nagatsu I (1993) Identification of L-DOPA immunoreactivity in some neurons in the human mesencephalic region: a novel DOPA neuron group? Neurosci Lett 157: 13–16

    Google Scholar 

  • Lannes B, Bernard V, Bloch B, Micheletti G (1995) Chronic treatment with dizocilpine maleate increases the number of striatal neurons expressing the D2 receptor gene. Neuroscience 65: 431–438

    Google Scholar 

  • Lehmann J, Langer SZ (1983) The striatal cholinergic interneuron: synaptic target of dopaminergic terminals? Neuroscience 10: 1105–1120

    Google Scholar 

  • Lindefors N, Ungerstedt (1990) Bilateral regulation of glutamate tissue and extracellular levels in caudate-putamen by midbrain dopamine neurons. Neurosci Lett 115: 248–252

    Google Scholar 

  • Löschmann PA, Lange KW, Kumow M, Rettig KJ, Jähnig P, Honoré T, Turski T, Wachtel H, Jenner P, Marsden CD (1991) Synergism of the AMPA-antagonist NBQX and the NMDA-antagonist CPP with L-Dopa in models of Parkinson's disease. J Neural Transm [PD-Sect] 3: 203–213

    Google Scholar 

  • Lozovsky D, Saller CF, Bayorh MA, Chiueh CC, Rice KC, Burke TR, Kopin IJ (1983) Effects of phencyclidine on rat prolactin, dopamine receptor and locomotor activity. Life Sci 32: 2725–2731

    Google Scholar 

  • Luquin MR, Obeso JA, Laguna J, Guillén J, Martinez-Lage JM (1993) The AMPA receptor antagonist NBQZ does not alter the motor response induced by selective dopamine agonists in MPTP-treated monkeys. Eur J Pharmacol235: 297–300

    Google Scholar 

  • Maj J, Rogoz Z, Skuza G (1993b) Central effects of CGP 37849 and CGP 39551, competitive NMDA receptor antagonists, in mice. Pol J Pharmacol 45: 349–360

    Google Scholar 

  • Maj J, Skuza G, Rogoz Z (1993b) Some central effects of CGP 37849 and CGP 39551, the competitive NMDA receptor antagonists: potential antiparkinsonian activity. J Neural Transm [PD-Sect] 6: 53–62

    Google Scholar 

  • Marsden CD, Obeso JA (1994) The functions of the basal ganglia and the paradox of stereotaxic surgery in Parkinson's disease. Brain 117: 877–897

    Google Scholar 

  • Meyerson BA, Linderoth B, Karlsson H, Ungerstedt U (1990) Microdialysis in the human brain: extracellular measurements in the thalamus of parkinsonian patients. Life Sci 46: 301–308

    Google Scholar 

  • Micheletti G, Lannes B, Haby C, Borrelli E, Kempf E, Warter JM, Zwiller J (1992) Chronic administration of NMDA antagonists induced D2 receptor synthesis in rat striatum. Brain Res 14: 363–368

    Google Scholar 

  • Miller WC, DeLong MR (1987) Altered tonic activity of neurons in the globus pallidus and subthalamic nucleus in the primate MPTP model of parkinsonism. In: Carpenter MB, Jayaraman A (eds) The basal ganglia II. Plenum Press, New York, pp 415–427

    Google Scholar 

  • Mintz I, Hammond C, Feger J (1986) Excitatory effect of iontophoretically applied dopamine on identified neurons of the rat subthalamic nucleus. Brain Res 375: 172–175

    Google Scholar 

  • Mitchell IJ, Clarke CE, Boyce S, Robertson RG, Peggs D, Sambrook MA, Crossman AR (1989) Neural mechanisms underlying parkinsonian symptoms based upon regional uptake of 2-deoxyglucose in monkeys exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neuroscience 32: 213–226

    Google Scholar 

  • Mitchell IJ, Lawson S, Moser B, Laidlaw SM, Cooper AJ, Walkinshaw G, Waters CM (1994) Glutamate-induced apoptosis results in a loss of striatal neurons in the parkinsonian rat. Neuroscience 63: 1–5

    Google Scholar 

  • Mitsushio H, Shiraymaa Y, Nishikawa T, Takahashi K (1993) Effects of subacute repeated injections of phencyclidine and MK-801 on substance P content in the rat brain. Regul Rept 46: 352–353

    Google Scholar 

  • Monaghan DT, Cotman CW (1985) Distribution of N-methyl-D-aspartate-sensitive L-[3H] glutamate-binding sites in rat brain. J Neurosci 5: 2909–2919

    Google Scholar 

  • Morelli M, Di Chiara G (1990) MK-801 potentiates dopaminergic D1 but reduces D2 responses in the 6-hydroxydopamine model of Parkinson's disease. EurJ Pharmacol 182: 611–612

    Google Scholar 

  • Morelli M, Fenu S, Pinna A, Di Chiara G (1992) Opposite effects of NMDA blockade on dopaminergic D1- and D2-mediated behaviour in the 6-hydroxydopamine model of turning: relationship with c-fos expression. J Pharmacol Exp Ther 290: 402–408

    Google Scholar 

  • Morelli M, Fenu S, Cozzolino A, Pinna A, Di Chiara G (1993) Blockade of muscarinic receptors potentiates D1 dependent turning behaviour and c-fos expression in 6-hydroxydopamine-lesioned rats but does not influence D2 mediated responses. Neuroscience 53: 673–678

    Google Scholar 

  • Nomoto N, Jenner PJ, Marsden CD (1985) The dopamine D2 agonist LY 141865, but not the D1 agonist SKF 38393 reverses parkinsonism induced by 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine (MPTP) in the common marmoset. Neurosci Lett 57: 37–41

    Google Scholar 

  • Ögren SO, Goldstein M (1994) Phencyclidine- and dizocilpine-induced hyperlocomotion are differentially mediated. Neuropsychopharmacology 11: 167–177

    Google Scholar 

  • Ossowska K (1994) The role of excitatory amino acids in experimental models of Parkinson's disease. J Neural Transm [PD Sect] 8: 39–71

    Google Scholar 

  • Pan HS, Walters JR (1988) Unilateral lesion of the nigrostriatal pathway decreases the firing rate and alters the firing pattern of globus pallidus neurons in the rat. Synapse 2: 650–659

    Google Scholar 

  • Parry TJ, Eberle-Wang K, Lucki I, Chesselet M-F (1994) Dopaminergic stimulation of subthalamic nucleus elicits oral dyskinesia in rats. Exp Neurol 128: 181–190

    Google Scholar 

  • Paul ML, Graybiel AM, David J-C, Robertson HA (1992) D1-like and D2-like dopamine receptors synergistically activate rotation and c-fos expression in the dopamine-depleted striatum in a rat model of Parkinson's disease. J Neurosci 12: 3729–3742

    Google Scholar 

  • Pierce RC, Rebec GV (1993) Intraneostriatal administration of glutamate antagonists increases behavioral activation and decreases neostriatal ascorbate via nondopaminergic mechanisms. J Neurosci 13: 4272–4280

    Google Scholar 

  • Pontieri FE, Morelli M, Orzi F, Terenzi R, Di Chiara G (1992) Metabolic mapping of the synergism between MK-801 and SKF 38393 in rats with unilateral lesions of the dopaminergic nigrostriatal pathway. Synapse 12: 225–260

    Google Scholar 

  • Rao TS, Kim HS, Lehmann J, Martin LL, Wood PL (1990) Interactions of phencyclidine receptor agonist MK-801 with dopaminergic system: regional studies in the rat. J Neurochem 54: 1157–1162

    Google Scholar 

  • Reid MS, Herrera-Marschitz M, Kehr J, Ungerstedt U (1990) Striatal dopamine and glutamate release: effects of intranigral injections of substance P. Acta Physiol Scand 140: 527–537

    Google Scholar 

  • Robertson GS, Vincent SR, Fibiger HC (1990) Striatonigral projection neurons contain D1 dopamine receptor-activated c-fos. Brain Res 523: 288–290

    Google Scholar 

  • Robertson HA (1992) Dopamine receptor interactions: some implications for the treatment of Parkinson's disease. Trends Neurosci 6: 201–206

    Google Scholar 

  • Ruzicka BB, Jhamandas K (1991) Met-enkephalin release from slices of the rat striatum and globus pallidus: stimulation by excitatory amino acids. J Pharmacol Exp Ther 257: 1025–1033

    Google Scholar 

  • Sarre S, De Klippel N, Herregodts P, Ebinger G, Michotte Y (1994) Biotransformation of locally applied L-dopa in the corpus striatum of the hemiparkinsonian rat studied with microdialysis. Naunyn Schmiedebergs Arch Pharmacol 350: 15–21

    Google Scholar 

  • Schmidt WJ, Bubser M, Hauber W (1992) Behavioural pharmacology of glutamate in the basal ganglia. J Neural Transm [Suppl] 38: 65–89

    Google Scholar 

  • Schwab RS, England AC, Poskanzer DC, Young RR (1969) Amantadine in the treatment of Parkinson's disease. JAMA 208: 1168–1170

    Google Scholar 

  • Sellal F, Hirsch E, Lisovski F, Mutschler V, Collard M, Marescaux C (1992) Contralateral disappearance of parkinsonian signs after subthalamic hematoma. Neurology 42: 255–256

    Google Scholar 

  • Setler PE, Malesky M, McDevitt J, Turner K (1978) Rotation produced by administration of dopamine and related substances directly into the supersensitive caudate nucleus. Life Sci 23: 1277–1284

    Google Scholar 

  • Singh NA, Midgley IP, Bush IG, Gibb JW, Hanson GR (1991) N-methyl-D-aspartate receptors mediate dopamine-induced changes in extrapyramidal and limbic dynorphin systems. Brain Res 555: 233–238

    Google Scholar 

  • Singh NA, Bush IG, Gibb JW, Hanson JR (1992) Role of N-methyl-D-aspartate receptors in dopamine D1-, but not D2-mediated changes in striatal and accumbens neurotensin systems. Brain Res 571: 260–264

    Google Scholar 

  • Skuza G, Rogoz Z, Quack G, Danysz W (1994) Memantine, amantadine, and L-deprenyl potentiate the action of L-DOPA in monoamine-depleted rats. J Neural Transm [Gen Sect] 98: 57–67

    Google Scholar 

  • Slusher BS, Rissolo KC, Jackson PF, Pullan LM (1994) Centrally-administered glycine antagonists increase locomotion in monoamine-depleted mice. J Neural Transm [Gen Sect] 97: 175–185

    Google Scholar 

  • Somers DL, Beckstead RM (1990) Striatal preprotachykinin and preproenkephalin mRNA levels and the levels of nigral substance P and pallidal Met5-enkephalin depend on corticostriatal axons that use the excitatory amino acid neurotransmitters aspartate and glutamate: quantitative radioimmunocytochemical and in situ hybridization evidence. Mol Brain Res 8: 143–158

    Google Scholar 

  • Starr MS (1995) Review: glutamate/dopamine D1/D2 balance in the basal ganglia and its relavance to Parkinson's disease. Synapse 19: 264–293

    Google Scholar 

  • Starr MS, Starr BS (1993a) Facilitation of dopamine D1 receptor- but not dopamine D1/ D2 receptor-dependent locomotion by glutamate antagonists in the reserpine-treated mouse. Eur J Pharmacol 250: 239–246

    Google Scholar 

  • Starr MS, Starr BS (1993b) Glutamate antagonists modify the motor stimulant actions of D1 and D2 agonists in reserpine-treated mice in complex ways that are not predictive of their interactions with the mixed D1/D2 agonist apomorphine. J Neural Transm [P-D Sect] 6: 215–226

    Google Scholar 

  • Starr MS, Starr BS (1994) Comparison of the effects of NMDA and AMPA antagonists on the locomotor activity induced by selective D1 and D2 dopamine agonists in reserpine-treated mice. Psychopharmacology 114: 469–476

    Google Scholar 

  • Starr MS, Starr BS (1995) Locomotor effects of amantadine in the mouse are not those of a typical glutamate antagonist. J Neural Transm [P-D Sect] 9: 31–43

    Google Scholar 

  • Starr MS, Summerhayes M (1982) Multifocal brain sites for apomorphine-induced circling and other stereotyped motor behaviour in the 6-hydroxydopamine-lesioned rat. Neurosci Lett 34: 277–282

    Google Scholar 

  • St-Pierre J-A, Bédard PJ (1994) Intranigaral but not intrastriatal microinjection of the NMDA antagonist MK-801 induced contralateral circling in the 6-OHDA rat model. Brain Res 660: 255–260

    Google Scholar 

  • St-Pierre J-A, Bédard PJ (1995) Systemic administration of the NMDA receptor antagonist MK-801 potentiates circling induced by intrastriatal microinjection of dopamine. Eur J Pharmacol 272: 123–129

    Google Scholar 

  • Svensson A, Carlsson ML (1992) Injection of the competitive NMDA receptor antagonist Ap-5 into the nucleus accumbens of monoamine-depleted mice induced pronounced locomotor stimulation. Neuropharmacology 31: 513–518

    Google Scholar 

  • Svensson A, Pileblad E, Carlsson M (1991) A comparison between the non-competitive NMDA antagonist dizocipline (MK-801) and the competitive NMDA antagonist DCPPene with regard to dopamine turnover and locomotor-stimulatory properties in mice. J Neural Transm [Gen Sect] 85: 117–129

    Google Scholar 

  • Svensson A, Carlsson ML, Carlsson A (1992a) Interaction between glutamatergic and dopaminergic tone in the nucleus accumbens of mice: evidence for a dual glutamatergic function with respect to psychomotor control. J Neural Transm [Gen Sect] 88: 235–240

    Google Scholar 

  • Svensson A, Carlsson A, Carlsson ML (1992b) Differential locomotor interactions between dopamine D1/D2 receptor agonists and the NMDA antogonist dizocilpine in monoamine-depleted mice. J Neural Transm [Gen Sect] 90: 199–217

    Google Scholar 

  • Svensson TH, Strömberg U (1970) Potentiation by amantadine hydrochloride of LDOPA-induced effects in mice. J Pharm Pharmacol 22: 639–640

    Google Scholar 

  • Taylor MD, De Ceballos ML, Rose S, Jenner P, Marsden CD (1992) Effects of a unilateral 6-hydroxydopamine lesion and prolonged L-3,4-dihydroxyphenylalanine treatment on peptidergic systems in rat basal ganglia. Eur J Pharmacol 219: 183–192

    Google Scholar 

  • Temlett JA, Quinn NP, Jenner PG, Marsden CD, Pourcher E, Bonnet A-M, Agid Y, Markstein R, Lataste X (1989) Antiparkinsonian activity of CY 208-243, a partial D-1 dopamine receptor agonist, in MPTP-treated marmosets and patients with Parkinson's disease. Mov Disord 4: 261–265

    Google Scholar 

  • Timmerman W, Zwaveling J, Westerink BHC (1991) Dopaminergic modulation of the GABA release in the substantia nigra reticulata. In: Rolleme H, Westerink B, Drijfhout WJ (eds) Monitoring molecules in neuroscience. Krips Repro, Meppel, The Netherlands, pp 105–107

    Google Scholar 

  • Trugman JM, Wooten GF (1987) Selective D1 and D2 dopamine agonists differentially alter basal ganglia glucose utilization in rats with unilateral 6-hydroxydopamine substantia nigra lesions. J Neurosci 7: 2927–2935

    Google Scholar 

  • Tsuda K, Tsuda S, Nishio I, Masuyama Y (1993) Effects of nicardipine on the release of acetylocholine in the rat central nervous system. Jap Circ J 57: 993–999

    Google Scholar 

  • Turski L, Schwarz M, Turski WA, Klockgether T, Sontag K-H, Collins JF (1985) Muscle relaxant action of excitatory amino acid antagonists. Neurosci Lett 53: 321–326

    Google Scholar 

  • Twery MJ, Thompson LA, Walters JR (1994) Intracellularly recorded response of rat striatal neurons in vitro to fenoldopam and SKF 38393 followmg lkesions of midbrain dopamine cells. Synapse 18: 67–78

    Google Scholar 

  • Van Zwieten-Boot BJ, Noach EL (1975) The effect of blocking depamine release on synthesis rate of dopamine in the striatum of the rat. Eur J Pharmacol 33: 247–254

    Google Scholar 

  • Verma A, Kulkarni SK (1992) Modulation of MK-801 response by dopaminergic agents in mice. Psychopharmacology 107: 431–436

    Google Scholar 

  • Wachtel H, Kunow M, Löschmann PA (1992) NBQX (6-nitro-sulfamoyl-benzoquinoxaline dione) and CPP (3-carboxy-piperazin-propyl phosphonic acid) potentiate dopamine agonist induced rotations in substantia nigra lesioned rats. Neurosci Lett 142: 179–182

    Google Scholar 

  • Waszczak BL (1990) Differential effects of D1 and D2 dopamine receptor agonists on substantia nigra pars reticulata neurons. Brain Res 513: 125–135

    Google Scholar 

  • Waszczak BL, Walters JR (1986) Endogenous dopamine can modulate inhibition of substantia nigra pars reticulata neurons elicited by GABA iontophoresis or striatal stimulation. J Neurosci 6: 120–126

    Google Scholar 

  • Weick BG, Walters JR (1987) Effects of D1 and D2 dopamine receptor stimulation on the activity of substantia nigra pars reticulata neurons in 6-hydroxydopamine lesioned rats: D1/D2 coactivation induces potentiated responses. Brain Res 405: 234–246

    Google Scholar 

  • Weihmuller FB, Ulas J, Nguyen I, Cotman CW, Marshall JF (1992) Elevated NMDA receptors in parkinsonian striatum. Neuroreport 3: 977–980

    Google Scholar 

  • Wüllner U, Kupsch A, Arnold G, Renner P, Scheid C, Scheid R, Oertel W, Klockgether T (1992) The competitive NMDA antagonist CGP 40116 enhances L-DOPA response in MPTP-treated marmosets. Neuropharmacology 31: 713–715

    Google Scholar 

  • Wüllner U, Brouillet E, Isaacson O, Young AB, Penney JB (1993) Glutamate receptor binding sites in MPTP-treated mice. Exp Neurol 121: 284–287

    Google Scholar 

  • Yamamoto BK, Davy S (1992) Dopaminergic modulation of glutamate release in striatum as measured by microdialysis. J Neurochem 58: 1736–1742

    Google Scholar 

  • Zadow B, Schmidt WJ (1994) The AMPA antagonists NBQX and GYKI 52466 do not counteract neuroleptic-induced catalepsy. Naunyn Schmiedebergs Arch Pharmacol 349: 61–65

    Google Scholar 

  • Ziolkowska B, Hollt V (1993) The NMDA receptor antagonist MK-801 markedly reduces the induction of c-fos gene by haloperidol in the mouse striatum. Neurosci Lett 156: 39–42

    Google Scholar 

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  1. M. S. Starr

    Present address: Department of Pharmacology, School of Pharmacy, University of London, 29-39 Brunswick Square, WC1N 1AX, London, UK

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    Starr, M.S. Antiparkinsonian actions of glutamate antagonists — alone and with L-DOPA: A review of evidence and suggestions for possible mechanisms. J Neural Transm Gen Sect 10, 141–185 (1995). https://doi.org/10.1007/BF02251229

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