Locomotor activity induced by MK-801 is enhanced in dopamine D3 receptor knockout mice but suppression by dopamine D3/D2 antagonists does not occur through the dopamine D3 receptor.
There are contradictory data regarding the role of the dopamine D(3) receptor in regulating N-methyl-d-aspartate (NMDA) receptor antagonist (e.g., dizocilpine) induced hyperactivity. The purpose of the present study was to examine the interaction of dopamine D(3) receptor preferring antagonists U99194A (5,6-dimethoxy-2(dipropylamino)indan) and S33804 ((3aR,9bS)-N[4-(8-cyano-1,3a,4,9b-tetrahydro-3H-benzopyrano[3,4-c]pyrrole-2-yl)-butyl] (4-phenyl)benzamide)) with dizocilpine (MK-801)-induced hyperactivity in wild type (WT) and dopamine D(3) receptor mutant (D(3)R KO) mice. D(3)R KO and WT mice were administered vehicle (saline, 1 ml/100g body weight, i.p.), or S33084 (1.0mg/kg.) and U99194A (0.1mg/kg or 0.01 mg/kg), and horizontal and vertical activity counts were recorded for 30 min. Mice were then treated with vehicle or MK-801 (0.12 mg/kg i.p.) and returned to the open field for an additional 55 min. D(3)R KO mice showed a significantly higher level of locomotor and rearing activity during the 1st 30 min after vehicle treatment compared to WT mice. MK-801-hyperactivity was significantly higher in D(3)R KO mice than WT mice. Dopamine D(3) receptor preferring antagonists suppressed the locomotor activity response to MK-801 to an equal extent in D(3)R KO and WT mice. The results confirm that MK-801-induced hyperactivity and novelty-induced behavioral activity and rearing are enhanced in D(3)R KO mice, but suppression by dopamine D(3) receptor preferring antagonists is not through dopamine D(3) receptor antagonism.
Yarkov
Alex V
AV
Center for Adaptive Neural Systems, PO Box 874404, Arizona State University, Tempe, AZ 85287-4404, United States. Alexandre.Iarkov@asu.edu
Der
Terry C
TC
Joyce
Jeffrey N
JN
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D055786:Gene Knockout Techniques; D005838:Genotype; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
D065127:Dopamine D2 Receptor Antagonists; D050637:Receptors, Dopamine D3; D016291:Dizocilpine Maleate