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Differential locomotor interactions between dopamine D1/D2 receptor agonists and the NMDA antagonist dizocilpine in monoamine-depleted mice

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Summary

Previous work in our laboratory has shown that the non-competitive N-methyl-D-aspartate antagonist dizocilpine (MK-801) interacts synergistically with the mixed dopamine (DA) receptor agonist apomorphine and the DA D 1 agonist SKF 38393 to promote locomotion in monoamine-depleted mice. The purpose of the present study was to compare the roles of DA D 1 and DA D 2 receptors in this interaction. To that end, dizocilpine was given in combination with either the DA D 1 receptor agonist SKF 38393 or the selective DA D 2 receptor agonist quinpirole or the preferential DA D 2 agonist bromocriptine. In general, the locomotor stimulatory effects produced by SKF 38393 were potentiated by dizocilpine, whereas the locomotor stimulation produced by quinpirole and bromocriptine was counteracted. However, baseline activity, which partly depends on how much time is allowed to elapse between administration of the DA agonist and commencement of locomotor recording, and partly on the dose of the DA agonist, seems to be an important factor that determines whether dizocilpine will have a weakening or a potentiating effect. Interestingly, the competitive NMDA antagonist D-CPPene displayed a different pattern of interaction with SKF 38393 and quinpirole in that synergistic effects were observed with both DA agonists, most conspicuously so with the DA D 2 receptor agonist.

The results are interpreted in the light of present knowledge of basal ganglia neuroanatomy; they are discussed in relation to the “direct” and “indirect” pathways from the striatum to the thalamus, proposed to form part of positive and negative cortico-striato-thalamo-cortical loops, respectively, as well as to the presumed presynaptic D 2 receptors on corticostriatal glutamatergic neurons.

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References

  • Abbott B, Starr BS, Starr MS (1991) CY 208-243 behaves as a typical D 1 agonist in the reserpine-treated mouse. Pharmacol Biochem Behav 38: 259–263

    PubMed  Google Scholar 

  • Alexander GE, Crutcher MD (1990) Functional architecture of basal ganglia circuits: neural substrates of parallel processing. TINS 13: 266–271

    Google Scholar 

  • Bischoff S, Heinrich M, Sonntag JM, Krauss J (1986) The D 1 dopamine receptor antagonist SCH 23390 also interacts potently with brain serotonin (5-HT2) receptors. Eur J Pharmacol 129: 367–370

    PubMed  Google Scholar 

  • Boldry RC, Uretsky NJ (1988) The importance of dopaminergic neurotransmission in the hypermotility response produced by the administration of N-methyl-D-aspartic acid into the nucleus accumbens. Neuropharmacology 27: 569–577

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Carlsson M, Svensson A (1990) The non-competitive NMDA antagonists MK-801 and PCP, as well as the competitive NMDA antagonist SDZ EAA 494 (D-CPPene), interact synergistically with clonidine to promote locomotion in monoamine-depleted mice. Life Sci 47: 1729–1736

    PubMed  Google Scholar 

  • Chandler CJ, Wohab W, Starr BS, Starr MS (1990) Motor depression: a new role for D1 receptors? Neuroscience 38: 437–445

    PubMed  Google Scholar 

  • Chevalier G, Deniau JM (1990) Disinhibition as a basic process in the expression of striatal functions. TINS 13: 277–280

    PubMed  Google Scholar 

  • Clark D, White FJ (1987) Review: D 1 dopamine receptor—the search for a function: a critical evaluation of the D 1/D 2 dopamine receptor classification and its functional implications. Synapse 1: 347–388

    PubMed  Google Scholar 

  • Coté L, Crutcher MD (1991) The basal ganglia. In: Kandel ER, Schwartz JH, Jessell TM (eds) Principles of neural science. Elsevier, Amsterdam, pp 647–659

    Google Scholar 

  • Flückiger E, Briner U, Enz A, Markstein R, Vigouret JM (1983) Dopaminergic ergot compounds: an overview. In: Calne DB, Horowski R, McDonald RJ, Wuttke W (eds) Lisuride and other dopamine agonists. Raven Press, New York, pp 1–9

    Google Scholar 

  • French ED, Ceci A (1990) Non-competitive N-methyl-D-aspartate antagonists are potent activators of ventral tegmental A 10 dopamine neurons. Neurosci Lett 119: 159–162

    PubMed  Google Scholar 

  • Galloway MP, Bencloucif S, Keegan MJ (1992) Effects of excitatory amino acid manipulation on serotonin facilitation of dopamine release on vivo microdialysis. Excitatory Amino Acids, Yosemite, California (Abstract, p 19)

    Google Scholar 

  • Garcia-Munoz M, Young SJ, Groves PM (1991 a) Terminal excitability of the corticostriatal pathway. II. Regulation by glutamate receptor stimulation. Brain Res 551: 207–215

    PubMed  Google Scholar 

  • Garcia-Munoz M, Young SJ, Groves PM (1991 b) Terminal excitability of the corticostriatal pathway. I. Regulation by dopamine receptor stimulation. Brain Res 551: 195–206

    PubMed  Google Scholar 

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

    PubMed  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: 15–26

    Google Scholar 

  • Graham WC, Robertson RG, Sambrook MA, Crossman AR (1990) Injection of excitatory amino acid antagonists into the medial pallidal segment of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated primate reverses motor symptoms of parkinsonism. Life Sci 47: 91–97

    Google Scholar 

  • Herrera-Marschitz M, Goiny M, Utsumi H, Ferre S, Guix T, Ungerstedt U (1990) Regulation of cortical and striatal dopamine and acetylcholine release by glutamate mechanism assayedin vivo with microdialysis:in situ stimulation with kainate-, quisqualateand NMDA-receptor agonists. In: Lubec G, Rosenthal GA (eds) Amino acids: chemistry, biology and medicine. ESCOM, Leiden, pp 599–604

    Google Scholar 

  • Hiramatsu M, Cho AK, Nabeshima T (1989) Comparison of the behavioural and biochemical effects of the NMDA receptor anatagonists, MK-801 and phencyclidine. Eur J Pharmacol 166: 359–366

    PubMed  Google Scholar 

  • Hyttel J (1983) SCH 23390 —the first selective dopamine D 1 antagonist. Eur J Pharmacol 91: 153–154

    PubMed  Google Scholar 

  • Jenkins OF, Jackson DM (1985) Bromocriptine potentiates the behavioural effects of directly and indirectly acting dopamine receptor agonists in mice. Naunyn-Schmie-debergs Arch Pharmacol 331: 7–11

    Google Scholar 

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

    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 monoaminedepleted rats and MPTP-treated monkeys. Ann Neurol 30: 717–723

    PubMed  Google Scholar 

  • Leviel V, Gobert A, Guibert B (1990) The glutamate-mediated release of dopamine in the rat striatum: further characterization of the dual excitatory-inhibitory function. Neuroscience 39: 305–312

    PubMed  Google Scholar 

  • Liljequist S (1991) Genetic differences in the effects of competitive and non-competitive NMDA receptor antagonists on locomotor activity in mice. Psychopharmacology 104: 17–21

    PubMed  Google Scholar 

  • Löschmann P-A, Lange KW, Kunow M, Rettig K-J, Jähnig P, Honoré T, Turski L, 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 

  • Meador-Woodruff JH, Mansour A, Healy DJ, Kuehn R, Zhou Q-Y, Bunzow JR, Akil H, Civelli O, Watson SJ (1991) Comparison of the distributions of D 1 and D 2 receptor mRNAs in rat brain. Neuropsychopharmacology 5: 231–242

    PubMed  Google Scholar 

  • Moghaddam B, Gruen RJ (1991) Do endogenous exicatory amino acids influence striatal dopamine release? Brain Res 544: 329–330

    PubMed  Google Scholar 

  • Moghaddam B, Gruen RJ, Roth RH, Bunney BS, Adams RN (1990) Effect of L-glutamate on the release of striatal dopamine: in vivo dialysis and electrochemical studies. Brain Res 518: 55–60

    PubMed  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. Eur J Pharmacol 182: 611–612

    PubMed  Google Scholar 

  • Nambu A, Yoshida S, Jinnai K (1990) Discharge pattern of pallidal neurons with input from various cortical areas during movement in the monkey. Brain Res 519: 183–191

    PubMed  Google Scholar 

  • Pan HS, Penney JB, Joung AB (1985) γ-aminobutyric acid and benzodiazepine receptor changes induced by unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. J Neurochem 45: 1396–1404

    PubMed  Google Scholar 

  • Penney JB, Young AB (1986) Striatal inhomogeneities and basal ganglia function. Mov Disord 1: 3–15

    PubMed  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

    PubMed  Google Scholar 

  • Reynolds IJ, Miller RJ (1988) Multiple sites for the regulation of the N-methyl-D-aspartate receptor. Mol Pharmacol 33: 581–584

    PubMed  Google Scholar 

  • Schultz W, Romo R (1990) Dopamine neurons of the monkey midbrain: contingencies of responses to stimuli eliciting immediate behavioral reactions. J Neurophysiol 63: 607–624

    PubMed  Google Scholar 

  • Skarsfeldt T, Larsen J-J (1988) SCH 23390-a selective dopamine D 1 receptor antagonist with putative 5-HT1 receptor agonist activity. Eur J Pharmacol 148: 389–395

    PubMed  Google Scholar 

  • Sonsalla PK, Nicklas WJ, Heikkila RE (1989) A role for excitatory amino acids in methamphetamine-induced nigrostriatal dopaminergic toxicity. Science 243: 398–400

    PubMed  Google Scholar 

  • Stoof JC, De Boer T, Sminia P, Mulder AH (1982) Stimulation of D 2-dopamine receptors in rat neostriatum inhibits the release of acetylcholine and dopamine but does not affect the release of g-aminobutyric acid, glutamate or serotonin. Eur J Pharmacol 84: 211–214

    PubMed  Google Scholar 

  • Svensson A, Pileblad E, Carlsson M (1991) A comparison between the non-competitive NMDA antagonist dizocilpine (MK-801) and the competitive NMDA antagonist D-CCPene 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 (1992) 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 TH (1992) Firing pattern of midbrain dopamine neurons in vivo: pharmacological analysis. 7th International Catecholamine Symposium, Amsterdam (Abstracts, p 305)

  • Tricklebank MD, Singh L, Oles RJ, Preston C, Iversen SD (1989) The behavioural effects of MK-801: a comparison with antagonists acting non-competitively and competitively at the NMDA receptor. Eur J Pharmacol 167: 127–135

    PubMed  Google Scholar 

  • Warenycia MW, McKenzie GM, Murphy M, Szerb JC (1987) The effects of cortical ablation on multiple unit activity in the striatum following dexamphetamine. Neuropharmacology 26: 1107–1114

    PubMed  Google Scholar 

  • Willetts J, Balster RL, Leander JD (1990) The behavioral pharmacology of NMDA receptor antagonist. TIPS 11: 423–428

    PubMed  Google Scholar 

  • Williams GV, Millar J (1990) Concentration-dependent action of stimulated dopamine release on neuronal activity in rat striatum. Neuroscience 39: 1–16

    PubMed  Google Scholar 

  • Zhang J, Chiodo LA, Freeman AS (1992) Electrophysiological effects of MK-801 on rat nigrostriatal and mesoaccumbal dopaminergic neurons. Brain Res (in press)

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  1. A. Carlsson

    Present address: Department of Pharmacology, University of Göteborg, Göteborg, Sweden

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  1. Department of Pharmacology, University of Göteborg, Göteborg, Sweden

    A. Svensson & M. L. Carlsson

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Svensson, A., Carlsson, A. & Carlsson, M.L. Differential locomotor interactions between dopamine D1/D2 receptor agonists and the NMDA antagonist dizocilpine in monoamine-depleted mice. J. Neural Transmission 90, 199–217 (1992). https://doi.org/10.1007/BF01250961

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