, Volume 123, Issue 2, pp 187–190 | Cite as

Effect of NMDA receptor antagonists on D1, D2 and D1/D2 mediated behaviors in intact rats

  • R. Dall'Olio
  • R. Rimondini
  • O. Gandolfi
Original Investigation


The effect of treatment with the competitive (CGP 43487) and non-competitive (MK-801) NMDA antagonists on behaviors induced by the stimulation of D1 (SKF 38393 induced grooming), D2 (LY 171555 elicited hypermotility) or D1/D2 (apomorphine induced locomotion and stereotypies) was observed in intact rats. The administration of low doses of MK-801 (0.03 and 0.06 mg/kg) or CGP 43487 (0.375 and 0.75 mg/kg), which were without effect by themselves on animal locomotion, reduced the hyperactivity induced by LY 171555 (0.15 mg/kg) and did not change the stimulating motor effect of a low dose of apomorphine (0.15 mg/kg). Spontaneous grooming behavior was inhibited by both NMDA antagonists, whereas the administration of CGP 43487 but not of MK-801 potentiated grooming response to SKF 38393 (10 mg/kg). Both antagonists increased stereotyped behavior induced by 0.25 mg/kg apomorphine. The results, according to those obtained by other authors in DA depleted/lesioned animals, support the view of interaction between NMDA/D1,D2 receptors in intact rats.

Key words

MK-801 CGP 43487 SKF 38393 induced grooming LY 171555 induced hypermotility Apomorphine-induced hypermotility and stereotyped behavior 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Boldry RC, Chase TN, Engber TM (1993) Influence of previous exposure to levodopa on the interaction between dizocilpine and dopamine D1 and D2 agonists in rats with 6-hydroxydopamine-induced lesions. J Pharmacol Exp Ther 267:1454–1459Google Scholar
  2. Chapman CD, Gazzara RA, Howard SG (1990) Effects of phencyclidine on extracellular levels of dopamine, dihydrophenylacetic acid and homovanillic acid in conscious and anesthetized rats. Neuropharmacology 29:319–325Google Scholar
  3. Dall'Olio R, Rimondini R, Gandolfi O (1995) The competitive NMDA antagonists CGP 43487 and APV potentiate dopaminergic function. Psychopharmacology 118:310–315Google Scholar
  4. Dawbarn D, Pycock CJ (1981) Motor effects following application of putative excitatory amino acid antagonists to the region of the mesencephalic dopamine cell bodies in the rat. Naunyn-Schmiedeberg's Arch Pharmacol 318:100–104Google Scholar
  5. Ferrè S, Gimenez-Lhart L, Artigas F, Martinez E (1994) Motor activation in short- and long-term, reserpinized mice: role ofN-methyl-d-aspartate, dopamine D1 and dopamine D2 receptors. Eur J Pharmacol 255:203–213Google Scholar
  6. Gandolfi O, Rimondini R, Dall'Olio R (1992) The modulation of dopaminergic transmission in the striatum by MK 801 is independent of presynaptic mechanisms. Neuropharmacology 31:1111–1114Google Scholar
  7. Kabuto H, Yokoi I, Mizukawa K, Mori A (1989) Effects of anN-methyl-d-aspartate receptor agonist and its antagonists CPP on the levels of dopamine and serotonin metabolites in rat striatum collected in vivo by using a brain dialysis technique. Neurochem Res 14:1075–1080Google Scholar
  8. Kaur S, Starr MS, Starr BS (1994) Role of D1 receptor mechanisms in the potentiation of motor responses tol-DOPA and apomorphine by MK801 in the reserpine-treated mouse. J Neural Transm [P-D Sect] 8:107–116Google Scholar
  9. Morelli M, Fenu S, Pinna A, Di Chiara G (1992) Opposite effects of NMDA receptor blockade on dopaminergic D1- and D2-mediated behavior in the 6-hydroxydopamine model of turning relationship with C-fos expression. J Pharmacol Exp Ther 260:402–408Google Scholar
  10. Starr MS, Starr BS (1993) Facilitation of dopamine D1 receptor- but not dopamine D1/D2 receptor - dependent locomotion by glutamate antagonists in reserpine-treated mouse. Eur J Pharmacol 250:239–246Google Scholar
  11. Starr MS, Starr BS (1994a) 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 114:469–476Google Scholar
  12. Starr MS, Starr BS (1994b) The new competitive NMDA receptor antagonistic CGP 40116 inhibits pilocarpine-induced limbic motor seizures and unconditioned motor behaviour in the mouse. Pharmacol Biochem Behav 47:127–131Google Scholar
  13. Verma A, Kulkarni SK (1992) Modulation of MK-801 response by dopaminergic agents in mice. Psychopharmacology 107:431–436Google Scholar
  14. Waters N, Svensson K, Haadsma-Svensson SR, Smith MW, Carlsson A (1993) The dopamine D3-receptor: a postsynaptic receptor inhibitory on rat locomotion activity. J Neural Transm [Gen Sect] 94:11–19Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • R. Dall'Olio
    • 1
  • R. Rimondini
    • 1
  • O. Gandolfi
    • 1
  1. 1.Department of PharmacologyUniversity of BolognaBolognaItaly

Personalised recommendations