Δ-Tetrahydrocannabinol Increases Dopamine D1-D2 Receptor Heteromer and Elicits Phenotypic Reprogramming in Adult Primate Striatal Neurons
| Autor: | Ahmed Hasbi, Bertha K. Madras, Jack Bergman, Stephen Kohut, Zhicheng Lin, Sarah L. Withey, Susan R. George |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | iScience, Vol 23, Iss 1, Pp - (2020) |
| Druh dokumentu: | article |
| ISSN: | 2589-0042 47122854 |
| DOI: | 10.1016/j.isci.2019.100794 |
| Popis: | Summary: Long-term cannabis users manifest deficits in dopaminergic functions, reflecting Δ9-tetrahydrocannabinol (THC)-induced neuroadaptive dysfunctional dopamine signaling, similar to those observed upon dopamine D1-D2 heteromer activation. The molecular mechanisms remain largely unknown. We show evolutionary and regional differences in D1-D2 heteromer abundance in mammalian striatum. Importantly, chronic THC increased the number of D1-D2 heteromer-expressing neurons, and the number of heteromers within individual neurons in adult monkey striatum. The majority of these neurons displayed a phenotype co-expressing the characteristic markers of both striatonigral and striatopallidal neurons. Furthermore, THC increased D1-D2-linked calcium signaling markers (pCaMKIIα, pThr75-DARPP-32, BDNF/pTrkB) and inhibited cyclic AMP signaling (pThr34-DARPP-32, pERK1/2, pS845-GluA1, pGSK3). Cannabidiol attenuated most but not all of these THC-induced neuroadaptations. Targeted pathway analyses linked these changes to neurological and psychological disorders. These data underline the importance of the D1-D2 receptor heteromer in cannabis use-related disorders, with THC-induced changes likely responsible for the reported adverse effects observed in heavy long-term users. : Drugs; Neuroscience; Cellular Neuroscience Subject Areas: Drugs, Neuroscience, Cellular Neuroscience |
| Databáze: | Directory of Open Access Journals |
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