Knockdown of Dopamine D2 Receptors in the Nucleus Accumbens Core Suppresses Methamphetamine-Induced Behaviors and Signal Transduction in Mice
| العنوان: | Knockdown of Dopamine D2 Receptors in the Nucleus Accumbens Core Suppresses Methamphetamine-Induced Behaviors and Signal Transduction in Mice |
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| المؤلفون: | Shin-ichi Muramatsu, Asako Iida, Yoshiaki Miyamoto, Atsumi Nitta, Keiji Sato |
| المصدر: | International Journal of Neuropsychopharmacology |
| بيانات النشر: | Oxford University Press, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, dopamine D2 receptors, nucleus accumbens, Genetic Vectors, Spatial Behavior, Nucleus accumbens, Epigenetics of cocaine addiction, Methamphetamine, Dopamine receptor D1, Dopamine, Dopamine receptor D2, Internal medicine, Conditioning, Psychological, medicine, Animals, Pharmacology (medical), Phosphorylation, Receptor, Cyclic AMP Response Element-Binding Protein, Extracellular Signal-Regulated MAP Kinases, Pharmacology, Chemistry, Receptors, Dopamine D2, Receptors, Dopamine D1, Dependovirus, Cell biology, Mice, Inbred C57BL, Psychiatry and Mental health, MicroRNAs, Endocrinology, Gene Knockdown Techniques, adeno-associated virus vectors, Central Nervous System Stimulants, Signal transduction, medicine.drug, Research Article, Akathisia, Drug-Induced, Signal Transduction |
| الوصف: | Background: Addictive drugs lead to reinforcing properties by increasing dopamine in the nucleus accumbens, which is composed of a core and shell regions. Neurons in the nucleus accumbens are divided into 2 subtypes based on the differential gene expression of the dopamine D1 receptors and D2 receptors. Methods: In the present study, we investigated the role of D2 receptors in the nucleus accumbens core in behaviors and signal transduction induced by psychostimulant methamphetamine in mice that were microinjected with adeno-associated virus vectors containing a microRNA (miRNA) sequence for D2 receptor (adeno-associated virus-miD2r vectors) in the nucleus accumbens core. The adeno-associated virus vectors containing a miRNA sequence for D2 receptor-treated mice (miD2r mice) were assessed at a reduction in D2 receptor, but at no change in dopamine D1 receptor, in the nucleus accumbens core compared with the adeno-associated virus-Mock vectors-treated mice (Mock mice). Results: miD2r mice exhibited a reduction in hyperlocomotion that was induced by a single treatment with methamphetamine. The development of locomotor sensitization induced by repeated treatment with methamphetamine exhibited less extension in miD2r mice. In a place conditioning paradigm, the preferred effects of methamphetamine were significantly weaker in miD2r mice than in Mock mice. Furthermore, the single treatment with methamphetamine-induced phosphorylation of extracellular signal regulated kinase and cyclic adenosine monophosphate response element-binding protein in the nucleus accumbens core of miD2r mice was decreased compared with that in Mock mice. Repeated treatment with methamphetamine-induced delta FBJ murine osteosarcoma viral oncogene homolog B accumulation in the nucleus accumbens core of miD2r mice was also attenuated. Conclusions: These findings suggest that a D2 receptor-mediated neuronal pathway from the nucleus accumbens core plays an inhibitory role in the development of reinforcing properties. |
| اللغة: | English |
| تدمد: | 1469-5111 1461-1457 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::54c80c9ebfbe3e0b640bf5c2a60196edTest http://europepmc.org/articles/PMC4360230Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....54c80c9ebfbe3e0b640bf5c2a60196ed |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14695111 14611457 |
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