Make up your mind - How stress and sex affect decision-making

Abstract

Decision-making refers to assessing costs and benefits of competing actions, with either a known outcome or an uncertain result. Decision-making depends on several abilities, such as behavioural flexibility and inhibiting risky responses. Several factors affect decision-making, causing differences in the outcome of decision-making processes. The overall aim was to improve our understanding of effects of stress and gender on decision-making, in rodents and in humans. First, impulsive decision-making was examined by testing male and female mice in a delay-discounting task. The data show that female mice shift more quickly from a large-late to a small-soon reward than male mice. While this suggests that female mice are more impulsive than male mice, an alternative explanation is that female mice are more exploratory than male mice and thus detect changes earlier. Factors like gender and internal state, but also handling-induced stress may affect task outcome. Therefore, home-cage testing has become popular. Here, a pilot study on home-cage testing of delay-discounting was conducted in rats. No differences were found in task-performance compared to traditional stand-alone tasks. Following from this, rats were tested in a home-cage setting in a more complex decision-making task: a new protocol to run a rodent version of the Iowa Gambling Task (IGT), a task for decision-making in humans. To validate this protocol, brain serotonin levels in rats were manipulated prior to testing their decision-making. As expected, lowering serotonin levels led to both poor decision-making and to gambling proneness. As increases in the stress hormone cortisol have been shown to disrupt IGT decision-making in men, time-dependent effects of corticosterone - the rodent equivalent of cortisol - on decision-making were addressed by treating male rats at two different time-points prior to testing in the rodent version of the IGT. Administration of corticosterone 30 min prior to testing disrupted reward-based decision-making. This was associated with increased c-Fos expression in a number of areas, i.e. the lateral orbitofrontal cortex, infralimbic cortex and insular cortex. Administration of corticosterone 3 hours prior to testing had no effect on task-performance. In line with systemic injections, infusions of corticosterone in the infralimbic cortex disrupted reward-based decision-making. The data for the lateral orbitofrontal cortex were inconclusive, possibly due to (unintended) damage, preventing treatment differences to be observed. Finally, time-dependent effects of stress on social decision-making were addressed. Earlier studies showed that experimentally induced stress in men is associated with lowered generosity, and altered altruistic punishment in a time-dependent manner. In contrast, women stress altruistic punishment or general altruism in women was not affected in a time-dependent manner by stress. This may be due to, among other things, the use of hormonal contraceptives, a condition that is associated with a more blunted stress-induced cortisol response. In professional environments, such as in health care, financial business, police and military, decisions are made under stress. Taking wrong decisions may have great personal and societal consequences. Therefore, increasing our knowledge of the differential effects of stress on decision-making in men and women, including the underlying brain circuits, is of great societal relevance.