Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1991 Aug;103(4):2037–2044. doi: 10.1111/j.1476-5381.1991.tb12372.x

R-(+)-HA-966, a glycine/NMDA receptor antagonist, selectively blocks the activation of the mesolimbic dopamine system by amphetamine.

P H Hutson 1, L J Bristow 1, L Thorn 1, M D Tricklebank 1
PMCID: PMC1908186  PMID: 1655150

Abstract

1. The effects of the glycine/NMDA receptor antagonist, (+)-HA-966 on the neurochemical and behavioural responses to amphetamine have been determined in the mouse and rat. 2. In vehicle-treated control mice, (+)-HA-966 (30-100 mg kg-1) did not affect dopamine synthesis in either the nucleus accumbens or striatum and was without marked effect on spontaneous locomotor activity. 3. In the mouse, (+)-HA-966 (30 and 100 mg kg-1) dose-dependently blocked the enhancement of dopamine synthesis induced in the nucleus accumbens by amphetamine, but was without effect on the increase in dopamine synthesis in the striatum. 4. Intracerebroventricular administration of the glycine/NMDA receptor antagonist, 5,7-dichlorokynurenic acid, in the mouse (10 micrograms) also significantly attenuated amphetamine-enhanced DOPA accumulation in the nucleus accumbens, but not in the striatum. 5. The decrease of dopamine synthesis in striatum and nucleus accumbens induced by the dopamine receptor agonist, apomorphine, was unaffected by (+)-HA-966 (100 mg kg-1). 6. (+)-HA-966 (30 mg kg-1) failed to attenuate the hyperactivity induced by the systemic administration of amphetamine in the mouse, but totally prevented the hyperlocomotion following infusion of amphetamine into the rat nucleus accumbens. In contrast, stereotyped behaviour induced by infusion of amphetamine into the rat striatum was not altered following pretreatment with (+)-HA-966 (30 mg kg-1). 7. The results are consistent with a selective facilitatory role of glycine/NMDA receptors on mesolimbic dopaminergic neurones.

Full text

PDF
2037

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anis N. A., Berry S. C., Burton N. R., Lodge D. The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. Br J Pharmacol. 1983 Jun;79(2):565–575. doi: 10.1111/j.1476-5381.1983.tb11031.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Carlsson A., Davis J. N., Kehr W., Lindqvist M., Atack C. V. Simultaneous measurement of tyrosine and tryptophan hydroxylase activities in brain in vivo using an inhibitor of the aromatic amino acid decarboxylase. Naunyn Schmiedebergs Arch Pharmacol. 1972;275(2):153–168. doi: 10.1007/BF00508904. [DOI] [PubMed] [Google Scholar]
  3. Carter C. J., L'Heureux R., Scatton B. Differential control by N-methyl-D-aspartate and kainate of striatal dopamine release in vivo: a trans-striatal dialysis study. J Neurochem. 1988 Aug;51(2):462–468. doi: 10.1111/j.1471-4159.1988.tb01061.x. [DOI] [PubMed] [Google Scholar]
  4. Christie M. J., Summers R. J., Stephenson J. A., Cook C. J., Beart P. M. Excitatory amino acid projections to the nucleus accumbens septi in the rat: a retrograde transport study utilizing D[3H]aspartate and [3H]GABA. Neuroscience. 1987 Aug;22(2):425–439. doi: 10.1016/0306-4522(87)90345-9. [DOI] [PubMed] [Google Scholar]
  5. Divac I., Fonnum F., Storm-Mathisen J. High affinity uptake of glutamate in terminals of corticostriatal axons. Nature. 1977 Mar 24;266(5600):377–378. doi: 10.1038/266377a0. [DOI] [PubMed] [Google Scholar]
  6. Donzanti B. A., Uretsky N. J. Effects of excitatory amino acids on locomotor activity after bilateral microinjection into the rat nucleus accumbens: possible dependence on dopaminergic mechanisms. Neuropharmacology. 1983 Aug;22(8):971–981. doi: 10.1016/0028-3908(83)90213-7. [DOI] [PubMed] [Google Scholar]
  7. Fonnum F., Storm-Mathisen J., Divac I. Biochemical evidence for glutamate as neurotransmitter in corticostriatal and corticothalamic fibres in rat brain. Neuroscience. 1981;6(5):863–873. doi: 10.1016/0306-4522(81)90168-8. [DOI] [PubMed] [Google Scholar]
  8. French E. D., Pilapil C., Quirion R. Phencyclidine binding sites in the nucleus accumbens and phencyclidine-induced hyperactivity are decreased following lesions of the mesolimbic dopamine system. Eur J Pharmacol. 1985 Oct 8;116(1-2):1–9. doi: 10.1016/0014-2999(85)90178-5. [DOI] [PubMed] [Google Scholar]
  9. Greenamyre J. T., Young A. B. Synaptic localization of striatal NMDA, quisqualate and kainate receptors. Neurosci Lett. 1989 Jun 19;101(2):133–137. doi: 10.1016/0304-3940(89)90519-3. [DOI] [PubMed] [Google Scholar]
  10. Grenhoff J., Tung C. S., Svensson T. H. The excitatory amino acid antagonist kynurenate induces pacemaker-like firing of dopamine neurons in rat ventral tegmental area in vivo. Acta Physiol Scand. 1988 Dec;134(4):567–568. doi: 10.1111/j.1748-1716.1998.tb08535.x. [DOI] [PubMed] [Google Scholar]
  11. Jhamandas K., Marien M. Glutamate-evoked release of endogenous brain dopamine: inhibition by an excitatory amino acid antagonist and an enkephalin analogue. Br J Pharmacol. 1987 Apr;90(4):641–650. doi: 10.1111/j.1476-5381.1987.tb11216.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kalivas P. W., Duffy P., Barrow J. Regulation of the mesocorticolimbic dopamine system by glutamic acid receptor subtypes. J Pharmacol Exp Ther. 1989 Oct;251(1):378–387. [PubMed] [Google Scholar]
  13. Kelley A. E., Domesick V. B. The distribution of the projection from the hippocampal formation to the nucleus accumbens in the rat: an anterograde- and retrograde-horseradish peroxidase study. Neuroscience. 1982 Oct;7(10):2321–2335. doi: 10.1016/0306-4522(82)90198-1. [DOI] [PubMed] [Google Scholar]
  14. Kim J. S., Hasller R., Hau P., Paik K. S. Effect of frontal cortex ablation on striatal glutamic acid level in rat. Brain Res. 1977 Aug 26;132(2):370–374. doi: 10.1016/0006-8993(77)90430-9. [DOI] [PubMed] [Google Scholar]
  15. Largent B. L., Gundlach A. L., Snyder S. H. Pharmacological and autoradiographic discrimination of sigma and phencyclidine receptor binding sites in brain with (+)-[3H]SKF 10,047, (+)-[3H]-3-[3-hydroxyphenyl]-N-(1-propyl)piperidine and [3H]-1-[1-(2-thienyl)cyclohexyl]piperidine. J Pharmacol Exp Ther. 1986 Aug;238(2):739–748. [PubMed] [Google Scholar]
  16. Lodge D., Johnson K. M. Noncompetitive excitatory amino acid receptor antagonists. Trends Pharmacol Sci. 1990 Feb;11(2):81–86. doi: 10.1016/0165-6147(90)90323-z. [DOI] [PubMed] [Google Scholar]
  17. Maragos W. F., Penney J. B., Young A. B. Anatomic correlation of NMDA and 3H-TCP-labeled receptors in rat brain. J Neurosci. 1988 Feb;8(2):493–501. doi: 10.1523/JNEUROSCI.08-02-00493.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. McGeer P. L., McGeer E. G., Scherer U., Singh K. A glutamatergic corticostriatal path? Brain Res. 1977 Jun 10;128(2):369–373. doi: 10.1016/0006-8993(77)91003-4. [DOI] [PubMed] [Google Scholar]
  19. Monaghan D. T., Cotman C. W. Distribution of N-methyl-D-aspartate-sensitive L-[3H]glutamate-binding sites in rat brain. J Neurosci. 1985 Nov;5(11):2909–2919. doi: 10.1523/JNEUROSCI.05-11-02909.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. O'Neill K. A., Carelli R. M., Jarvis M. F., Liebman J. M. Hyperactivity induced by N-methyl-d-aspartate injections into nucleus accumbens: lack of evidence for mediation by dopaminergic neurons. Pharmacol Biochem Behav. 1989 Dec;34(4):739–745. doi: 10.1016/0091-3057(89)90268-2. [DOI] [PubMed] [Google Scholar]
  21. Pulvirenti L., Swerdlow N. R., Koob G. F. Microinjection of a glutamate antagonist into the nucleus accumbens reduces psychostimulant locomotion in rats. Neurosci Lett. 1989 Aug 28;103(2):213–218. doi: 10.1016/0304-3940(89)90578-8. [DOI] [PubMed] [Google Scholar]
  22. Roberts P. J., Anderson S. D. Stimulatory effect of L-glutamate and related amino acids on [3H]dopamine release from rat striatum: an in vitro model for glutamate actions. J Neurochem. 1979 May;32(5):1539–1545. doi: 10.1111/j.1471-4159.1979.tb11096.x. [DOI] [PubMed] [Google Scholar]
  23. Roberts P. J., Sharif N. A. Effects of l-glutamate and related amino acids upon the release of [3H]dopamine from rat striatal slices. Brain Res. 1978 Nov 24;157(2):391–395. doi: 10.1016/0006-8993(78)90048-3. [DOI] [PubMed] [Google Scholar]
  24. Samuel D., Errami M., Nieoullon A. Localization of N-methyl-D-aspartate receptors in the rat striatum: effects of specific lesions on the [3H]3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid binding. J Neurochem. 1990 Jun;54(6):1926–1933. doi: 10.1111/j.1471-4159.1990.tb04893.x. [DOI] [PubMed] [Google Scholar]
  25. Seutin V., Verbanck P., Massotte L., Dresse A. Evidence for the presence of N-methyl-D-aspartate receptors in the ventral tegmental area of the rat: an electrophysiological in vitro study. Brain Res. 1990 Apr 23;514(1):147–150. doi: 10.1016/0006-8993(90)90448-k. [DOI] [PubMed] [Google Scholar]
  26. Shimizu N., Duan S. M., Hori T., Oomura Y. Glutamate modulates dopamine release in the striatum as measured by brain microdialysis. Brain Res Bull. 1990 Jul;25(1):99–102. doi: 10.1016/0361-9230(90)90258-2. [DOI] [PubMed] [Google Scholar]
  27. Singh L., Donald A. E., Foster A. C., Hutson P. H., Iversen L. L., Iversen S. D., Kemp J. A., Leeson P. D., Marshall G. R., Oles R. J. Enantiomers of HA-966 (3-amino-1-hydroxypyrrolid-2-one) exhibit distinct central nervous system effects: (+)-HA-966 is a selective glycine/N-methyl-D-aspartate receptor antagonist, but (-)-HA-966 is a potent gamma-butyrolactone-like sedative. Proc Natl Acad Sci U S A. 1990 Jan;87(1):347–351. doi: 10.1073/pnas.87.1.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Singh L., Menzies R., Tricklebank M. D. The discriminative stimulus properties of (+)-HA-966, an antagonist at the glycine/N-methyl-D-aspartate receptor. Eur J Pharmacol. 1990 Sep 4;186(1):129–132. doi: 10.1016/0014-2999(90)94069-a. [DOI] [PubMed] [Google Scholar]
  29. Snell L. D., Mueller Z. L., Gannon R. L., Silverman P. B., Johnson K. M. A comparison between classes of drugs having phencyclidine-like behavioral properties on dopamine efflux in vitro and dopamine metabolism in vivo. J Pharmacol Exp Ther. 1984 Nov;231(2):261–269. [PubMed] [Google Scholar]
  30. Vignon J., Pinet V., Cerruti C., Kamenka J. M., Chicheportiche R. [3H]N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine ([3H]BTCP): a new phencyclidine analog selective for the dopamine uptake complex. Eur J Pharmacol. 1988 Apr 13;148(3):427–436. doi: 10.1016/0014-2999(88)90122-7. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES