Stress-induced risk aversion is reverted by a D2-D3 agonist

1. Stress-induced risk aversion is reverted by a D2-D3 agonist Morgado P1,2, Marques F1,2, Ribeiro B1,2, Sousa N1,2and Cerqueira JJ1,2 1Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; 2ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal pedromorgado@ecsaude.uminho.pt • Exposure to stress can lead to cognitive and behavioral impairments that can influence the decision making processes. We have previously shown that chronic stress bias decisions from goal directed to habit based behaviours and that this was correlated with changes in neuronal circuits involving different areas of the prefrontal cortex and striatum. • Risk-based decisions require complex processes that are known to be mediated by the mesocorticolimbic dopamine (DA) system. • We hypothesized that chronic stress can alter the pattern of choices in a decision-making task and that these alterations could be reverted by augmenting the DA activity. In this work, we further explored the impact of chronic stress in decision-making using a new 5-hole paradigm. Introduction Results When compared with neutral condition average, percentage of safe choices decreases in risk favorable condition and increases in safe favorable condition. This indicates that animals are sensible to changes in outcome values. During the learning period, the number of trials consistently increases while the total time decreases. This clearly shows that animals learn the task. Experimental Design 8d. 8d. 8d. Vehicle Vehicle Vehicle Training Handling Quinpirole Quinpirole Quinpirole C-fosanalysis Vehicle Vehicle Vehicle Stress Quinpirole Quinpirole Quinpirole C-fosexpression analysis revealed that this task is dependent on activation of medial pre-frontal cortex, orbitrofrontal cortex, insular cortex and striatal areas. 15d. 28d. Neutral RiskFav. Safe Fav. In all three different paradigms, chronic stressed animals display significantly higher rates of safe choiceswhem compared with controls. This effect is reverted by chronic administration of D2/D3 dopamine agonist quinpirole. • DecisionMakingParadigm • 5-hole operating box was transformed into a risky decision-making test: • each daily session ends after 100 choices or 30 minutes (whichever comes first); • animals have to choose between safe and risk options; • safe option is the choice of a hole which always delivers a small reward; • risk option is the choice of a hole which has a 25% probability of delivering a big reward; • light is used to cue risk holes and its location is randomly assigned in each trial. Exposure to stress leads to higher activation of the lateral part of orbitofrontal cortex and in the insular cortex. Methods These results suggest that chronic stress produces a risk-aversive pattern of choice that can be reverted by D2/D3 activation. These effect seems to be mediated by an over activation of lateral part of orbitofrontal cortex and in the insular cortex. • Neurosciences Research Domain • University of Minho – Portugal • www.icvs.uminho.pt Conclusions aperture food dispenser