On the roles of dopamine D-1 vs. D-2 receptors for the hyperactivity response elicited by MK-801

J Neural Transm Gen Sect. 1994;95(2):113-21. doi: 10.1007/BF01276430.


The present study was aimed at clarifying to what extent the hypermotility induced by the uncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801 depends on dopamine (DA) D-1 compared to D-2 receptor tone. The D-1 receptor antagonist SCH 23390 was found to reduce locomotion to a greater extent in MK-801-treated than in vehicle-treated mice, whereas the reverse appeared to be the case for the DA D-2 receptor antagonist raclopride. In other words, MK-801-induced hyperactivity was more readily antagonized by SCH 23390 than by raclopride and, thus, DA D-1 receptors seem to be more important than D-2 receptors for MK-801-induced hyperactivity. These results are in line with our previous observation that MK-801 generally interacts synergistically with a DA D-1 but not with a D-2 receptor agonist in monoamine-depleted mice. In view of the possible role of deficient glutamatergic neurotransmission in schizophrenia, our findings underline the importance of investigating the efficacy of selective DA D-1 antagonists in this disorder.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzazepines / pharmacology
  • Dizocilpine Maleate / pharmacology
  • Dizocilpine Maleate / toxicity*
  • Hyperkinesis / chemically induced*
  • Hyperkinesis / physiopathology
  • Hyperkinesis / prevention & control
  • Male
  • Mice
  • Raclopride
  • Receptors, Adrenergic, alpha-2 / drug effects
  • Receptors, Adrenergic, alpha-2 / physiology
  • Receptors, Dopamine D1 / drug effects
  • Receptors, Dopamine D1 / physiology*
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Dopamine D2 / physiology*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Salicylamides / pharmacology
  • Schizophrenia / physiopathology
  • Yohimbine / pharmacology


  • Benzazepines
  • Receptors, Adrenergic, alpha-2
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, N-Methyl-D-Aspartate
  • Salicylamides
  • Yohimbine
  • Raclopride
  • Dizocilpine Maleate