title: Stress induced risk-aversion is reverted by D2/D3 agonist in the rat.
abstract: Stress exposure triggers cognitive and behavioral impairments that influence decision-making processes. Decisions under a context of uncertainty require complex reward-prediction processes that are known to be mediated by the mesocorticolimbic dopamine (DA) system in brain areas sensitive to the deleterious effects of chronic stress, in particular the orbitofrontal cortex (OFC). Using a decision-making task, we show that chronic stress biases risk-based decision-making to safer behaviors. This decision-making pattern is associated with an increased activation of the lateral part of the OFC and with morphological changes in pyramidal neurons specifically recruited by this task. Additionally, stress exposure induces a hypodopaminergic status accompanied by increased mRNA levels of the dopamine receptor type 2 (Drd2) in the OFC; importantly, treatment with a D2/D3 agonist quinpirole reverts the shift to safer behaviors induced by stress on risky decision-making. These results suggest that the brain mechanisms related to risk-based decision-making are altered after chronic stress, but can be modulated by manipulation of dopaminergic transmission.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.; ICVS-3Bs PT Government Associate Laboratory, Braga, Guimarães, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Morgado
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.; ICVS-3Bs PT Government Associate Laboratory, Braga, Guimarães, Portugal.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Marques
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.; ICVS-3Bs PT Government Associate Laboratory, Braga, Guimarães, Portugal.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Ribeiro
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.; ICVS-3Bs PT Government Associate Laboratory, Braga, Guimarães, Portugal.
authors.forename: Hugo
authors.initials: H
authors.lastname: Leite-Almeida
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.; ICVS-3Bs PT Government Associate Laboratory, Braga, Guimarães, Portugal.
authors.forename: José M
authors.initials: JM
authors.lastname: Pêgo
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.; ICVS-3Bs PT Government Associate Laboratory, Braga, Guimarães, Portugal.
authors.forename: Ana J
authors.initials: AJ
authors.lastname: Rodrigues
authors.affiliation: Department of Pharmacology, Medical School, University of Athens, Athens, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Dalla
authors.affiliation: Department of Pharmacology, Medical School, University of Athens, Athens, Greece; First Department of Psychiatry, Eginition Hospital, Medical School, University of Athens, Athens, Greece.
authors.forename: Nikos
authors.initials: N
authors.lastname: Kokras
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.; ICVS-3Bs PT Government Associate Laboratory, Braga, Guimarães, 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, Portugal.; ICVS-3Bs PT Government Associate Laboratory, Braga, Guimarães, Portugal. Electronic address: jcerqueira@ecsaude.uminho.pt.
authors.forename: João J
authors.initials: JJ
authors.lastname: Cerqueira
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003657:Decision Making / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019257:Quinpirole / Q000494:pharmacology; D012333:RNA, Messenger; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000378:metabolism*; D012309:Risk-Taking; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D035501:Uncertainty
chemical_list: C000607792:DRD2 protein, rat; D018491:Dopamine Agonists; C493595:Drd3 protein, rat; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D019257:Quinpirole; D004298:Dopamine
keywords: Decision-making; Dopamine; Insula; Orbitofrontal; Quinpirole; Stress