Skip to main content
Log in

Glycine site antagonists abolish dopamine D 2 but not D 1 receptor mediated catalepsy in rats

  • Full Papers
  • Published:
Journal of Neural Transmission / General Section JNT Aims and scope Submit manuscript

Summary

Catalepsy—a state of postural immobility (akinesia) with muscular rigidity (rigor)—and reduced locomotion in animals are behavioral deficits showing similarities with symptoms of Parkinson's disease (PD). The effects of the glycine site antagonists 7-chlorokynurenate and (R)-HA-966 on haloperidol-(D2 antagonist) and SCH 23390-(D 1 antagonist) induced catalepsy and reduced locomotion are investigated in rats. Both antagonists dose-dependently counteract dopamine D 2 receptor mediated catalepsy but they have no influence on locomotion. Neither 7-chlorokynurenate nor (R)-HA-966 has any effect on dopamine D 1 receptor mediated catalepsy.

This finding is surprising, since NMDA receptor antagonists counteract both, dopamine D 1 and D 2 receptor mediated catalepsy. D 1 and D 2 receptors are located on different populations of neurons. Thus, the present findings suggest that these different neuronal populations have different sensitivity for ligands binding at the glycine binding site of the NMDA receptor.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Albin RL, Makowiec RL, Hollingsworth ZR, Dure IV LS, Penny JB, Young AB (1992) Excitatory amino acid binding sites in the basal ganglia of the rat: quantitative autoradiographic study. Neuroscience 46/1: 35–48

    Google Scholar 

  • Alexander GE, DeLong MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Ann Rev Neurosci: 357–381

  • Bédard PJ, Boucher R, Gomez-Mancilla B, Blandette P (1992) Primate models of Parkinson's disease. In: Boulton A, Baker G, Butterworth R (eds) Neuromethods, vol 21. Animal models of neurological disease, I. Human Press, New York, pp 159–173

    Google Scholar 

  • Bouyer JJ, Park DH, Joh TH, Pickel VM (1984) Chemical and structural analysis of the relation between cortical inputs and tyrosine hydroxylase-containing terminals in rat striatum. Brain Res 302: 267–276

    Google Scholar 

  • Bristow LJ, Hutson PH, Thorn L, Tricklebank (1993) The glycine/NMDA receptor antagonist, R-(+)-HA-966, blocks activation of the mesolimbic dopamine system induced by phencyclidine and dizocilpine (MK-801) in rodents. Br J Pharmacol 108: 1156–1163

    Google Scholar 

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

    Google Scholar 

  • Calderon SF, Sanberg PR, Norman AB (1988) Quinolinic acid lesions of rat striatum abolish D 1- and D2-dopamine receptor-mediated catalepsy. Brain Res 450: 403–407

    Google Scholar 

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

    Google Scholar 

  • Colpaert FC (1987) Pharmacological characteristics of tremor, rigidity, and hypokinesia induced by reserpine in rat. Neuropharmacology 26: 1431–1440

    Google Scholar 

  • Elliott PJ, Close SP, Walsh DM, Hayes AG, Marriott AS (1990) Neuroleptic-induced catalepsy as a model of Parkinson's disease. II. Effects of glutamate antagonists. J Neural Transm [PDSect] 2: 91–100

    Google Scholar 

  • Gerfen CR, Engber TM, Mahan LC, Sussel Z, Chase TN, Monsma FJ, Sibley DR (1990) D 1 and D 2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science 250: 1429–1432

    Google Scholar 

  • Graybiel AM (1984) Neurochemically specified subsystems in the basal ganglia. In: Pitman (ed) Functions of the basal ganglia. Ciba Foundation Symposium 107, London, pp 114–149

  • Harrison MB, Wiley RG, Wooten GF (1992) Changes in D 2 but not D 1 receptor binding in the striatum following a selective lesion of striatopallidal neurons. Brain Res 590: 305–310

    Google Scholar 

  • Hauber W (1992) Anti-akinetic and anti-bradykinetic effects of NMDA antagonists in a rodent model of Parkinson's disease. In: Elsner N, Richter DW (eds) Rhythmogenesis in neurons and networks — Proceedings of the 20th Göttingen Neurobiology Conference. Thieme, Stuttgart, pp 593

  • Hauber W, Schmidt WJ (1993) Discrete quinolinic acid lesion of the lateral but not of the medial caudate/putamen reversed haloperidol induced catalepsy in rats. J Neural Transm [Gen Sect] 94: 103–114

    Google Scholar 

  • Hutson PH, Bristow LJ, Thorn L, Tricklebank MD (1991) R-(+)-HA-966, a glycine/NMDA receptor antagonist, selectively blocks the activation of the mesolimbic dopamine system by amphetamine. Br J Pharmacol 103: 2037–2044

    Google Scholar 

  • Jolicoeur FB, Rivest R (1992) Rodent models of Parkinson's disease. In: Boulton A, Baker G, Butterworth R (eds) Neuromethods, vol 21. Animal models of neurological disease, I. Human Press, New York, pp 135–158

    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 

  • Kretschmer BD, Zadow B, Volz TL, Volz L, Schmidt WJ (1992) The contribution of the different binding sites of the N-methyl-D-aspartate (NMDA) receptor to the expression of behavior. J Neural Transm [GenSect] 87: 23–35

    Google Scholar 

  • Kutsuwada T, Kashiwabuchi N, Mori H, Sakimura K, Kushiya E, Araki K, Meguro H, Masaki H, Kumanishi T, Arakawa M, Mishina M (1992) Molecular diversity of the NMDA receptor channel. Nature 358: 36–41

    Google Scholar 

  • Monaghan DT, Olverman HJ, Nguyen L, Watkins JC, Cotman CW (1988) Two classes of N-methyl-D-aspartate recognition sites: differential distribution of differential regulation by glycine. Proc Natl Acad Sci USA 85: 9836–9840

    Google Scholar 

  • Monyer H, Sprengel R, Schoepfer R, Herb A, Higuchi M, Lomeli H, Burnashey N, Sakmann B, Seeburg PH (1992) Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science 256: 1217–1221

    Google Scholar 

  • Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, Sydney

    Google Scholar 

  • Rabey JM, Nissipeanu P, Korczyn AD (1992) Efficacy of memantine, an NMDA receptor antagonist, in the treatment of Parkinson's disease. J Neural Transm [P-D Sect] 4: 277–282

    Google Scholar 

  • Robertson GS, Vincent SR, Fibiger HC (1992) D 1 and D 2 dopamine receptors differentially regulate c-fos expression in striatonigral and striatopallidal neurons. Neuroscience 49/2: 285–296

    Google Scholar 

  • Ross RT (1990) Drug-induced Parkinsonism and other movement disorders. Can J Neurol Sci 17: 155–162

    Google Scholar 

  • Sakurai SY, Penny JB, Young AB (1993) Regionally distinct N-methyl-D-aspartate receptors distinguished by quantitative autoradiography of [3H]MK-801 binding in rat brain. J Neurochem 60: 1344–1353

    Google Scholar 

  • Sanberg PR, Bunsey MD, Giordano M, Norman AB (1988) The catalepsy test its ups and downs. Behav Neurosci 102: 748–759

    Google Scholar 

  • Scheel-Krüger J (1983) The GABA receptor and animal behavior—evidence that GABA transmits and mediates dopaminergic functions in the basal ganglia and the limbic system. In: Enna SJ (ed) The GABA receptors. The Human Press, New Jersey, pp 215–256

    Google Scholar 

  • Schmidt WJ, Bubser M (1989) Anticataleptic effects of the N-methyl-D-aspartate antagonist MK-801 in rats. Pharmacol Biochem Behav 32: 621–623

    Google Scholar 

  • Schmidt WJ, Bubser M, Hauber W (1990) Anticataleptic effects of NMDA receptor antagonists. Eur J Neurosci [Suppl 3]: 118

    Google Scholar 

  • Schmidt WJ, Zadow B, Kretschmer BD, Hauber W (1991) Anticataleptic potencies of glutamate-antagonists. Amino Acids 1: 225–237

    Google Scholar 

  • Smith AD, Bolam JP (1990) The neural network of the basal ganglia as revealed by the study of synaptic connections of identified neurones. Trends Neurosci 13/7: 259–265

    Google Scholar 

  • Standaert DG, Testa CM, Penny JB, Young AB (1993) Alternatively spliced isoforms of the NMDA-R 1 glutamate receptor subunit: differential expression in the basal ganglia of the rat. Neurosci Lett 152: 161–164

    Google Scholar 

  • Surmeier DJ, Eberwine J, Wilson CJ, Cao A, Stefani A, Kitai ST (1992) Dopamine receptor subtypes colocalize in rat striatonigral neurons. Proc Natl Acad Sci USA 89: 10178–10182

    Google Scholar 

  • Verma A, Kulkarni SK (1992) D1/D2 dopamine and N-methyl-D-aspartate (NMDA) receptor participation in experimental catalepsy in rats. Psychopharmacology 109: 477–483

    Google Scholar 

  • Wachtel H (1991) Antiparkinsonian dopamine agonists: a review of the pharmacokinetics and neuropharmacology in animal and humans. J Neural Transm [P-D Sect] 3: 151–201

    Google Scholar 

  • Wroblewski JT, Danysz W (1989) Modulation of glutamate receptors. Molecular mechanism and functional implications. Ann Rev Pharmacol Toxicol 29: 441–474

    Google Scholar 

  • Yoshida Y, Ono T, Kizu A, Fukushima R, Miyagishi T (1991) Striatal N-methyl-D-aspartate receptors in haloperidol-induced catalepsy. Eur J Pharmacol 203: 173–180

    Google Scholar 

  • Zahm DS, Brog JS (1992) On the significance of subterritories in the “accumbens” part of the rat ventral striatum. Neuroscience 50/4: 751–767

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kretschmer, B.D., Winterscheid, B., Danysz, W. et al. Glycine site antagonists abolish dopamine D 2 but not D 1 receptor mediated catalepsy in rats. J. Neural Transmission 95, 123–136 (1994). https://doi.org/10.1007/BF01276431

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01276431

Keywords

Navigation