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
| Autor: | Alex V. Yarkov, Terry C. Der, Jeffrey N. Joyce |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Genotype medicine.drug_class Gene Knockout Techniques Mice chemistry.chemical_compound Dopamine receptor D3 Dopamine Internal medicine medicine Animals Neurotransmitter Pharmacology Behavior Animal Receptors Dopamine D3 Dopamine antagonist Receptor antagonist Dizocilpine Dopamine D2 Receptor Antagonists Endocrinology chemistry Catecholamine NMDA receptor Female Dizocilpine Maleate Locomotion medicine.drug |
| Zdroj: | European Journal of Pharmacology. 627:167-172 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2009.10.068 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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