On the roles of dopamine D-1 vs. D-2 receptors for the hyperactivity response elicited by MK-801.
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.
Martin
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P
Department of Pharmacology, University of Göteborg, Sweden.
Svensson
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A
Carlsson
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Carlsson
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ML
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology / Q000633:toxicity*; D006948:Hyperkinesis / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D051379:Mice; D020891:Raclopride; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012457:Salicylamides / Q000494:pharmacology; D012559:Schizophrenia / Q000503:physiopathology; D015016:Yohimbine / Q000494:pharmacology
D001552:Benzazepines; D018341:Receptors, Adrenergic, alpha-2; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D012457:Salicylamides; D015016:Yohimbine; D020891:Raclopride; D016291:Dizocilpine Maleate