title: Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation.
abstract: Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Here we demonstrate that the pattern of activation of D1 and D2 neurons in the nucleus accumbens (NAc) predicts motivational drive, and that optogenetic activation of either neuronal population enhances motivation in mice. Using a different approach in rats, we further show that activating NAc D2 neurons increases cue-induced motivational drive in control animals and in a model that presents anhedonia and motivational deficits; conversely, optogenetic inhibition of D2 neurons decreases motivation. Our results suggest that the classic view of D1-D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga 4710-057, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães 4710-057, Portugal.
authors.forename: Carina
authors.initials: C
authors.lastname: Soares-Cunha
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga 4710-057, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães 4710-057, Portugal.
authors.forename: Barbara
authors.initials: B
authors.lastname: Coimbra
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga 4710-057, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães 4710-057, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: David-Pereira
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga 4710-057, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães 4710-057, Portugal.
authors.forename: Sonia
authors.initials: S
authors.lastname: Borges
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga 4710-057, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães 4710-057, Portugal.
authors.forename: Luisa
authors.identifier: 0000-0002-7724-0446
authors.initials: L
authors.lastname: Pinto
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga 4710-057, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães 4710-057, Portugal.
authors.forename: Patricio
authors.initials: P
authors.lastname: Costa
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga 4710-057, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães 4710-057, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Sousa
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga 4710-057, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães 4710-057, Portugal.
authors.forename: Ana J
authors.initials: AJ
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D041722:Genes, Transgenic, Suicide; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009042:Motivation / Q000187:drug effects / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D012201:Reward
chemical_list: D017448:Receptors, Dopamine D2; D003042:Cocaine