title: Increasing dopamine D2 receptor expression in the adult nucleus accumbens enhances motivation.
abstract: A decrease in dopamine D2 receptor (D2R) binding in the striatum is one of the most common findings in disorders that involve a dysregulation of motivation, including obesity, addiction and attention deficit hyperactivity disorder. As disruption of D2R signaling in the ventral striatum--including the nucleus accumbens (NAc)--impairs motivation, we sought to determine whether potentiating postsynaptic D2R-dependent signaling in the NAc would improve motivation. In this study, we used a viral vector strategy to overexpress postsynaptic D2Rs in either the NAc or the dorsal striatum. We investigated the effects of D2R overexpression on instrumental learning, willingness to work, use of reward value representations and modulation of motivation by reward associated cues. Overexpression of postsynaptic D2R in the NAc selectively increased motivation without altering consummatory behavior, the representation of the value of the reinforcer, or the capacity to use reward associated cues in flexible ways. In contrast, D2R overexpression in the dorsal striatum did not alter performance on any of the tasks. Thus, consistent with numerous studies showing that reduced D2R signaling impairs motivated behavior, our data show that postsynaptic D2R overexpression in the NAc specifically increases an animal's willingness to expend effort to obtain a goal. Taken together, these results provide insight into the potential impact of future therapeutic strategies that enhance D2R signaling in the NAc.
authors.affiliation: Department of Neuroscience, Columbia University, New York, NY, USA.
authors.forename: P
authors.initials: P
authors.lastname: Trifilieff
authors.forename: B
authors.initials: B
authors.lastname: Feng
authors.forename: E
authors.initials: E
authors.lastname: Urizar
authors.forename: V
authors.initials: V
authors.lastname: Winiger
authors.forename: R D
authors.initials: RD
authors.lastname: Ward
authors.forename: K M
authors.initials: KM
authors.lastname: Taylor
authors.forename: D
authors.initials: D
authors.lastname: Martinez
authors.forename: H
authors.initials: H
authors.lastname: Moore
authors.forename: P D
authors.initials: PD
authors.lastname: Balsam
authors.forename: E H
authors.initials: EH
authors.lastname: Simpson
authors.forename: J A
authors.initials: JA
authors.lastname: Javitch
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003214:Conditioning, Classical; D003216:Conditioning, Operant; D005786:Gene Expression Regulation / Q000502:physiology*; D005822:Genetic Vectors / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009042:Motivation / Q000502:physiology*; D009714:Nucleus Accumbens / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012201:Reward; D014316:Tritium / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D017448:Receptors, Dopamine D2; D014316:Tritium; D049452:Green Fluorescent Proteins