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MHC class I in dopaminergic neurons suppresses relapse to reward seeking

Major histocompatibility complex class I (MHCI) is an important immune protein that is expressed in various brain regions, with its deficiency leading to extensive synaptic transmission that results in learning and memory deficits. Although MHCI is highly expressed in dopaminergic neurons, its role...

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Detalles Bibliográficos
Autores principales: Murakami, Gen, Edamura, Mitsuhiro, Furukawa, Tomonori, Kawasaki, Hideya, Kosugi, Isao, Fukuda, Atsuo, Iwashita, Toshihide, Nakahara, Daiichiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5851664/
https://www.ncbi.nlm.nih.gov/pubmed/29546241
http://dx.doi.org/10.1126/sciadv.aap7388
Descripción
Sumario:Major histocompatibility complex class I (MHCI) is an important immune protein that is expressed in various brain regions, with its deficiency leading to extensive synaptic transmission that results in learning and memory deficits. Although MHCI is highly expressed in dopaminergic neurons, its role in these neurons has not been examined. We show that MHCI expressed in dopaminergic neurons plays a key role in suppressing reward-seeking behavior. In wild-type mice, cocaine self-administration caused persistent reduction of MHCI specifically in dopaminergic neurons, which was accompanied by enhanced glutamatergic synaptic transmission and relapse to cocaine seeking. Functional MHCI knockout promoted this addictive phenotype for cocaine and a natural reward, namely, sucrose. In contrast, wild-type mice overexpressing a major MHCI gene (H2D) in dopaminergic neurons showed suppressed cocaine seeking. These results show that persistent cocaine-induced reduction of MHCI in dopaminergic neurons is necessary for relapse to cocaine seeking.