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Introduction

Decision-making in a rat gambling task is modulated by D2/D3 receptors Morgado P 1,2 , Ribeiro B 1,2 , Almeida A 1,2 , Sousa N 1,2 and Cerqueira JJ 1,2 1 Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal

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Introduction

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  1. Decision-making in a rat gambling task is modulated by D2/D3 receptors Morgado P1,2, Ribeiro B1,2, Almeida A1,2, Sousa N1,2 and Cerqueira JJ1,2 1Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal 2ICVS/3B’s - PT GovernmentAssociateLaboratory, Braga/Guimarães, Portugal pedromorgado@ecsaude.uminho.pt Supported by FEDER funds through Operational program for competitivity factors – COMPETE and by national funds through FCT – Foundation for Science and Technology to project “PTDC/SAU-NSC/111814/2009” Conclusions References Introduction Results Experimental procedures • Making decisions based on the probability of future events is routine in our everyday life. Individuals perceive and respond to uncertain outcomes and can also change their responses according to reward value or task difficulty. • Evaluation of risks and rewards associated with different options requires complex processes that assign value to rewards. Since these processes are known to be mediated by the mesocorticolimbic dopamine (DA) system, we hypothesized that augmenting DA activity could affect the pattern of choice in a gambling task. • To test this hypothesis, we developed a new gambling task using the 5-hole operating box. 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 • Animals were trained for 15 days and then tested in 3 consecutive 9-day tests: • in the first, safe and risk choices were rewarded with 1 and 4 pellets, respectively, resulting in no net gain (neutral condition); • in the second, risk choice reward was doubled (1 to 8), resulting in a long-term profit for those who risk (risk favorable condition); • in the third, reward in safe choices was doubled (2 to 4), resulting in a long-term profit for that choice (safe favorable condition). • In the last 3 days of each period, half of the animals received i.p. injections of the dopamine D2/D3 agonist quinpirole (0.15 mg/kg) and controls received vehicle. 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. Quinpirole-treated animals (n=10) display lower rates of safe choices when compared with controls, in all testing conditions (neutral, risk favorable, safe favorable). Quinpirole resulted in an average reduction of safe choices of 17,7%, 18,4% and 22,3% in the neutral, risk favorable and safe favorable conditions, respectively, in treated animals compared with controls. • 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. aperture food dispenser • Our results suggest that acute activation of D2/D3 receptors bias decisions involving evaluation of risk/reward towards risky choices, even when these are already more profitable (suggesting an absence of a ceiling effect); • This results are in accordance with previous data reporting effects of D2/D3 agonists and amphetamines on risk based decision-making. Flagel SB, Clark JJ, Robinson TE, Mayo L, Czuj A, Willuhn I, Akers CA, Clinton SM, Phillips PM, Akil H (2011). A selective role for dopamine in stimulus–reward learning. Nature 469(7328): 53–57. Onge JR , Chiu YC, Floresco SB(2010). Differential effects of dopaminergic manipulations on risky choice. Psychopharmacology. 211: 209–221. Zeeb FD, Robbins TW, Winstanley CA(2009). Serotonergic and Dopaminergic Modulation of Gambling Behavior as Assessed Using a Novel Rat Gambling Task. Neuropsychopharmacology . 34: 2329–2343. Neurosciences Research Domain University of Minho – Portugal www.icvs.uminho.pt

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