Δ-Tetrahydrocannabinol Increases Dopamine D1-D2 Receptor Heteromer and Elicits Phenotypic Reprogramming in Adult Primate Striatal Neurons.

ABSTRACT: 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, BDN

SUBMITTER: Hasbi A 

PROVIDER: S-EPMC6971351 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature