title: Genetic reconstruction of dopamine D1 receptor signaling in the nucleus accumbens facilitates natural and drug reward responses.
abstract: The dopamine D1 receptor (D1R) facilitates reward acquisition and its alteration leads to profound learning deficits. However, its minimal functional circuit requirement is unknown. Using conditional reconstruction of functional D1R signaling in D1R knock-out mice, we define distinct requirements of D1R in subregions of the nucleus accumbens (NAc) for specific dimensions of reward. We demonstrate that D1R expression in the core region of the NAc (NAc(Core)), but not the shell (NAc(Shell)), enhances selectively a unique form of pavlovian conditioned approach and mediates D1R-dependent cocaine sensitization. However, D1R expression in either the NAc(Core) or the NAc(Shell) improves instrumental responding for reward. In contrast, neither NAc(Core) nor NAc(Shell) D1R is sufficient to promote motivation to work for reward in a progressive ratio task or for motor learning. These results highlight dissociated circuit requirements of D1R for dopamine-dependent behaviors.
authors.affiliation: Department of Pharmacology and Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington 98053, USA.
authors.forename: Bryan B
authors.initials: BB
authors.lastname: Gore
authors.forename: Larry S
authors.initials: LS
authors.lastname: Zweifel
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage; D003042:Cocaine / Q000008:administration & dosage; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D018491:Dopamine Agonists / Q000008:administration & dosage; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism*; D012201:Reward; D045442:Rotarod Performance Test; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*
chemical_list: D001552:Benzazepines; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D017447:Receptors, Dopamine D1; C098593:dopamine D1A receptor; D049452:Green Fluorescent Proteins; C067113:SK&F 81297; D003042:Cocaine