Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation.

Bibliographic Details
Main Author: Cunha, Catarina Soares
Publication Date: 2016
Other Authors: Coimbra, Bárbara Guimarães Salazar, Pereira, Ana David, Borges, Sónia Maria de Sousa, Costa, Patrício Soares, Sousa, Nuno, Rodrigues, Ana João, Pinto, Luisa
Format: Article
Language: eng
Source: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Download full: http://hdl.handle.net/1822/45144
Summary: 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.
id RCAP_28d71bbab203d8b8b51f7c600d52c696
oai_identifier_str oai:repositorium.sdum.uminho.pt:1822/45144
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation.Science & TechnologyStriatal 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.A special acknowledgement to Karl Deisseroth from Stanford University, for providing viral constructs and for comments on the manuscript, and to Alan Dorval from the University of Utah, for providing mouse strains. Thanks to Luis Jacinto, Joao Oliveira and Joana Silva that helped in some technical aspects of the experiments. C.S.-C., B.C., A.D.-P. and S.B. are recipients of Fundacao para a Ciencia e Tecnologia (FCT) fellowships (SFRH/BD/51992/2012; SFRH/BD/98675/2013; SFRH/BD/90374/2012; SFRH/BD/89936/2012). A.J.R. is a FCT Investigator (IF/00883/2013). This work was co-financed by the Portuguese North Regional Operational Program (ON.2 - O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER). Part of the work was supported by the Janssen Neuroscience Prize (1st edition).info:eu-repo/semantics/publishedVersionNature Publishing GroupUniversidade do MinhoCunha, Catarina SoaresCoimbra, Bárbara Guimarães SalazarPereira, Ana DavidBorges, Sónia Maria de SousaCosta, Patrício SoaresSousa, NunoRodrigues, Ana JoãoPinto, Luisa2016-06-072016-06-07T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/45144eng2041-172310.1038/ncomms1182927337658http://www.nature.com/info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:16:13Zoai:repositorium.sdum.uminho.pt:1822/45144Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:08:44.831416Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation.
title Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation.
spellingShingle Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation.
Cunha, Catarina Soares
Science & Technology
title_short Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation.
title_full Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation.
title_fullStr Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation.
title_full_unstemmed Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation.
title_sort Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation.
author Cunha, Catarina Soares
author_facet Cunha, Catarina Soares
Coimbra, Bárbara Guimarães Salazar
Pereira, Ana David
Borges, Sónia Maria de Sousa
Costa, Patrício Soares
Sousa, Nuno
Rodrigues, Ana João
Pinto, Luisa
author_role author
author2 Coimbra, Bárbara Guimarães Salazar
Pereira, Ana David
Borges, Sónia Maria de Sousa
Costa, Patrício Soares
Sousa, Nuno
Rodrigues, Ana João
Pinto, Luisa
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Cunha, Catarina Soares
Coimbra, Bárbara Guimarães Salazar
Pereira, Ana David
Borges, Sónia Maria de Sousa
Costa, Patrício Soares
Sousa, Nuno
Rodrigues, Ana João
Pinto, Luisa
dc.subject.por.fl_str_mv Science & Technology
topic Science & Technology
description 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.
publishDate 2016
dc.date.none.fl_str_mv 2016-06-07
2016-06-07T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/45144
url http://hdl.handle.net/1822/45144
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2041-1723
10.1038/ncomms11829
27337658
http://www.nature.com/
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
_version_ 1799132510394777600