Susanne Koot MAKE UP YOUR MIND how stress and sex affect decision-making Cover design Proefschrift-aio.nl Lay-out and design Proefschrift-aio.nl Printed by DPP ISBN 978-90-393-6034-7 © 2013 Susanne Koot MAKE UP YOUR MIND how stress and sex affect decision-making BESLISSEN Proefschrift Hoe stress en sekse keuzegedrag beïnvloeden ter verkrijging van de graad van doctor (met een samenvatting in aan de Universiteit Utrecht op gezag van het Nederlands) de rector magnificus, prof.dr. G.J. van der Zwaan, ingevolge het besluit van het college voor promoties in het openbaar te verdedigen op woensdag 16 oktober 2013 des ochtends te 10.30 uur door Susanne Koot geboren op 12 juni 1983 te Nijmegen Promotoren Prof. dr. M. Joëls Prof. dr. L.J.M.J. Vanderschuren Co-promotor Dr. R. van den Bos Printing of this thesis was financially supported by PRS Italia, Rome, Italy. TABLE OF CONTENTS CH. 1 General Introduction 7 CH. 2 Gender differences in delay-discounting under mild food 23 restriction CH. 3 Home cage testing of delay-discounting in rats 43 CH. 4 Compromised decision-making and increased gambling 57 proneness following dietary serotonin depletion in rats CH. 5 Time-dependent effects of corticosterone on reward-based 81 decision-making in a rodent model of the Iowa Gambling Task CH. 6 Corticosterone and decision-making in male Wistar rats: 99 the effect of corticosterone application in the infralimbic and orbitofrontal cortex CH. 7 Temporal domains in social decision-making following stress 113 in women CH. 8 General Discussion 131 References 143 Nederlandse samenvatting 173 Curriculum vitae 181 List of publications 183 Dankwoord | Acknowledgements 185 1 6 CHAPTER 1 GENERAL INTRODUCTION 1 What is decision-making? 8 2 Modelling decision-making 9 2.1 Delay-discounting and gambling (risk-proneness) 9 2.2 Iowa Gambling Task 12 2.3 Social decision-making 14 3 Neural substrates 14 4 Research themes of this thesis 17 4.1 Stress and decision-making 17 4.2 Gender differences and decision-making 18 5 Outline of the thesis 19 7 1 What is decision-making? Both humans and other animals make decisions throughout life. These may be big decisions about how to organise your professional and personal life, but also more 1 trivial daily choices like what to eat. Let’s take this example here: foraging behaviour. Suppose you are in the supermarket for your daily groceries and you are thinking about what to have for dinner. Do you fancy something healthy, or rather something fast and comforting? How much does each meal cost? Perhaps it is worth to go to another supermarket for something in discount. But what if you were a rodent? Imagine you are a rat living in the suburbs of a city like Rome. You are hungry, so you have to go out to find some food. You can stay comfortable and close by in the sewing system, finding some low energetic and rotten vegetables of the daily market. Or you could travel a bit further towards the city centre, taking some more effort and risk when going above ground. There you can scatter in a restaurant’s trash bin for the leftovers of a good smelling pasta carbonara, prepared by a famous Italian cook. However, apart from the fact that it takes a lot of energy to get there, there is also the chance that you encounter a big rat from nearby. He might be higher up in hierarchy, munching on that pasta carbonara already, ready to kick you out of the trash bin. Or, even worse, you could run accidentally into the restaurant’s cat, and already his smell stresses you out. Such stories, for rats or humans, can be described for many behavioural domains, whether related to food, shelter, sexual partners or social environment. And, in addition, in humans for job-related or private contexts. However, in essence they all boil down to the same thing: decision-making is related to assessing costs and benefits of competing actions with either a known outcome or an uncertain result. Decision-making is comprised of several abilities, such as flexibility in behaviour, inhibition of responses to immediate rewards in order to weigh long and short term losses and benefits, and continuous evaluation of the risks and rewards of various options. Impairments in these abilities, necessary for optimal decision-making, can have tremendous influence on daily life. This is particularly apparent in psychiatric disorders, such as pathological gambling, attention deficit hyperactivity disorder and drug addiction, in which impulsivity and decision-making are disrupted. To be able to treat these disorders, but also to understand the impact of e.g. stress and other neuromodulators like serotonin on these processes, unravelling the underlying mechanisms is demanded. Here, I will focus on two aspects associated with decision- making, which recently have gained more and more interest: the effects of stress and gender differences. Decisions are often made under stressful conditions, but unlike domains as memory, the effects of stress on a complex process like decision-making performance are still not fully understood. Likewise, the neurotransmitter serotonin is an important candidate for the modulation of decision-making, but clear evidence and how it relates to e.g. pathological gambling is still sparse. Furthermore, only recently gender differences in decision-making, and particularly the effects of stress thereon, were acknowledged, but it is still not understood very well where these differences originate from and what they imply. With this thesis I will contribute to the knowledge of these processes in these fields. In this Introduction, I will first outline how decision-making can be tested in a laboratory setting in humans and other animals, focussing on the tasks used in 8 GENERAL INTRODUCTION this thesis. Subsequently, the neural substrates that underlie decision-making will be indicated briefly. Finally, the effects of stress on choice behaviour and gender differences in decision-making, the central themes of this thesis, will be introduced. This introduction ends with an outline of the experimental chapters and the general discussion. 2 Modelling decision-making Decision-making in humans and animals has been modelled in many different ways (for reviews see e.g. Brand et al. 2006; De Visser et al. 2011c; Floresco et al. 2008; Weber and Johnson, 2009). Basically all these tasks involve a cost-benefit analysis of competing actions that differ in immediate and/or long-term gains and losses. In humans benefits are often framed as monetary wins, while costs are often represented as monetary losses or delays before gratification. In animals, benefits are often framed as palatable food pellets, while costs are often represented as delays before gratification, physical exercise (lever presses or barriers) or punishments (shock, unpalatable food). Here only those tasks are described which are used in the studies presented in this thesis: delay-discounting and probability-related tasks, the Iowa Gambling Task and social decision-making tasks. Human decision-making is largely mirrored in animal choice behaviour (Van Wingerden and Kalenscher, 2012), making it relevant to use animal models for the investigation of the mechanisms underlying decision-making. One important reason to use animal models of decision-making behaviour is the wide range of techniques available in animal modelling, which makes it possible to resolve causal contributions of brain regions, and to perform pharmacological manipulations which are technically or ethically impossible in human subjects (Kalenscher and Van Wingerden, 2011). Another reason for using animal models of decision-making is the study of the evolutionary roots of human decision-making, sharing neural substrates underlying choice behaviour with animals (Kalenscher and Van Wingerden, 2011). 2.1 Delay-discounting and gambling (risk-proneness) Many paradigms, involving a choice with delayed and/or uncertain reinforcers, have been developed in order to test the self-control abilities and/or impulsive decision- making (Evenden, 1999). Of the three dimensions of impulsivity (motor, attentional and non-planning; Moeller et al. 2001; Patton et al. 1995), here I focus on non- planning or impulsive decision-making, reflecting a lack of regard for the future (Winstanley, 2011). Temporal or delay discounting is a reduction in the subjective value of a delayed outcome (Hamilton and Potenza, 2012). The delay-discounting task measures impulsive choice, in which subjects have to choose between a small immediate reward and a large delayed reward. When testing humans or monkeys, the subjects can choose between a small immediate reward and a larger delayed reward, often both presented on a screen, by pushing the corresponding response button (Evenden, 1999; Homberg, 2012; Monterosso and Ainslie, 1999; Reynolds and Schiffbauer, 2004). Similarly, rodents can choose between an immediately available food pellet and a higher number of food pellets after a certain delay, by responding 9 to either of two operant levers in a Skinner box (figure 1). Despite the similarity between the two test situations, there are also obvious differences (see also below). For instance, in animals, before the testing phase with delayed rewards starts, they are first trained to prefer a large reward over a small one; human subjects instead 1 are given written instructions that they can choose between a small reward now and a large reward within a couple of months. Note that animals are offered a real reward during testing, while human subjects are provided a hypothetical reward, possibly becoming real after the completion of the test. Subjects are expected to shift their preference from the large/delayed to the small/immediate reinforcer as a consequence of late reward delivery (Adriani et al. 2004; Evenden and Ryan, 1996). Impulsive subjects in particular are intolerant to situations in which reward is delayed: smaller, immediate reinforcers are preferred to larger rewards that are available only after a delay (Evenden and Ryan, 1996; Evenden, 1999).