title: Mechanisms underlying differential D1 versus D2 dopamine receptor regulation of inhibition in prefrontal cortex.
abstract: Typically, D1 and D2 dopamine (DA) receptors exert opposing actions on intracellular signaling molecules and often have disparate physiological effects; however, the factors determining preferential activation of D1 versus D2 signaling are not clear. Here, in vitro patch-clamp recordings show that DA concentration is a critical determinant of D1 versus D2 signaling in prefrontal cortex (PFC). Low DA concentrations (<500 nm) enhance IPSCs via D1 receptors, protein kinase A, and cAMP. Higher DA concentrations (>1 microm) decrease IPSCs via the following cascade: D2-->G(i)-->platelet-derived growth factor receptor--> increase phospholipase C--> increase IP3--> increase Ca2+--> decrease dopamine and cAMP-regulated phosphoprotein-32--> increase protein phosphatase 1/2A--> decrease GABA(A). Blockade of any molecule in the D2-linked pathway reveals a D1-mediated increase in IPSCs, suggesting that D1 effects are occluded at higher DA concentrations by this D2-mediated pathway. Thus, DA concentration, by acting through separate signaling cascades, may determine the relative amount of cortical inhibition and thereby differentially regulate the tuning of cortical networks.
authors.affiliation: Physiology and Neuroscience Department, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Trantham-Davidson
authors.forename: Laurence C
authors.initials: LC
authors.lastname: Neely
authors.forename: Antonieta
authors.initials: A
authors.lastname: Lavin
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Seamans
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D005680:gamma-Aminobutyric Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D004298:Dopamine