title: Activation of Dopamine D1 Receptors Regulates Dendritic Morphogenesis Through Rac1 and RhoA in Prefrontal Cortex Neurons.
abstract: Dopamine (DA) is an important regulator of neuronal plasticity in the prefrontal cortex (PFC) and plays a critical role in addiction-related neuroadaptation. The Rho GTPases, including Rac1, RhoA and Cdc42, are key regulators of actin cytoskeleton rearrangement that play important roles in dendritic morphogenesis. The goal of the current study was to use cultures of primary PFC neurons to gain a better understanding of the molecular mechanisms underlying DA-induced dendritic morphogenesis, a phenomenon that mimics the increase in DA synaptic transmission observed in the PFC of in vivo cocaine administration. We investigated the effects of repeated DA treatments on dendritic morphology changes in PFC neurons, and identified Rac1 and RhoA as downstream effectors of D1 receptors during the regulation of dendritic morphogenesis. Importantly, we found that D1 receptor-regulated Rac1 and RhoA have distinct roles in the regulation of dendritic morphogenesis after repeated DA treatments. Our data provide the first evidence that Rac1 and RhoA are effectors of D1 receptor signaling during dendritic morphogenesis and represent new signaling molecules involved in long-lasting neuroadaptation in the PFC.
authors.affiliation: Key Laboratory of Functional Proteomics of Guangdong Province, Department of Pathophysiology, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Jingjing
authors.initials: J
authors.lastname: Gu
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Minjuan
authors.initials: M
authors.lastname: Xie
authors.forename: Lu
authors.initials: L
authors.lastname: Huang
authors.forename: Yutong
authors.initials: Y
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Jinhua
authors.initials: J
authors.lastname: Xue
authors.forename: Fukun
authors.initials: F
authors.lastname: Guo
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001552:Benzazepines / Q000494:pharmacology; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D009024:Morphogenesis / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D001552:Benzazepines; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; C067113:SK&F 81297; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein