AUTHOR=Nishi Akinori , Kuroiwa Mahomi , Shuto Takahide 

TITLE=Mechanisms for the Modulation of Dopamine D1 Receptor Signaling in Striatal Neurons

JOURNAL=Frontiers in Neuroanatomy

VOLUME=5

YEAR=2011

URL=https://www.frontiersin.org/journals/neuroanatomy/articles/10.3389/fnana.2011.00043

DOI=10.3389/fnana.2011.00043

ISSN=1662-5129

ABSTRACT=<p>In the striatum, dopamine D<sub>1</sub> receptors are preferentially expressed in striatonigral neurons, and increase the neuronal excitability, leading to the increase in GABAergic inhibitory output to substantia nigra pars reticulata. Such roles of D<sub>1</sub> receptors are important for the control of motor functions. In addition, the roles of D<sub>1</sub> receptors are implicated in reward, cognition, and drug addiction. Therefore, elucidation of mechanisms for the regulation of dopamine D<sub>1</sub> receptor signaling is required to identify therapeutic targets for Parkinson’s disease and drug addiction. D<sub>1</sub> receptors are coupled to G<sub>s/olf</sub>/adenylyl cyclase/PKA signaling, leading to the phosphorylation of PKA substrates including DARPP-32. Phosphorylated form of DARPP-32 at Thr34 has been shown to inhibit protein phosphatase-1, and thereby controls the phosphorylation states and activity of many downstream physiological effectors. Roles of DARPP-32 and its phosphorylation at Thr34 and other sites in D<sub>1</sub> receptor signaling are extensively studied. In addition, functional roles of the non-canonical D<sub>1</sub> receptor signaling cascades that coupled to G<sub>q</sub>/phospholipase C or Src family kinase become evident. We have recently shown that phosphodiesterases (PDEs), especially PDE10A, play a pivotal role in regulating the tone of D<sub>1</sub> receptor signaling relatively to that of D<sub>2</sub> receptor signaling. We review the current understanding of molecular mechanisms for the modulation of D<sub>1</sub> receptor signaling in the striatum.</p>