Sex differences in a rat model of risky decision making.

Abstract

Many debilitating psychiatric conditions, including drug addiction, are characterized by poor decision making and maladaptive risk-taking. Recent research has begun to probe this relationship to determine how brain mechanisms mediating risk-taking become compromised after chronic drug use. Currently, however, the majority of work in this field has used male subjects. Given the well-established sex differences in drug addiction, it is conceivable that such differences are also evident in risk-based decision making. To test this possibility, male and female adult rats were trained in a “Risky Decision making Task” (RDT), in which they chose between a small, “safe” food reward and a large, “risky” food reward accompanied by an increasing probability of mild footshock punishment. Consistent with findings in human subjects, females were more risk averse, choosing the large, risky reward significantly less than males. This effect was not due to differences in shock reactivity or body weight, and risk-taking in females was not modulated by estrous phase. Systemic amphetamine administration decreased risk-taking in both males and females; however, females exhibited greater sensitivity to amphetamine, suggesting that dopaminergic signaling may partially account for sex differences in risk-taking. Finally, although males displayed greater instrumental responding for food reward, reward choice in the RDT was not affected by satiation, indicating that differences in motivation to obtain food reward cannot fully account for sex differences in risk-taking. These results should prove useful for developing targeted treatments for psychiatric conditions in which risk-taking is altered and that are known to differentially affect males and females.

Deciphering Decision Making: Variation in Animal Models of Effort- and Uncertainty-Based Choice Reveals Distinct Neural Circuitries Underlying Core Cognitive Processes

“…Although acute administration of the psychostimulants amphetamine and caffeine decreased high effort choice in workers, these drugs either had the opposite or null effects on slackers' choice, respectively (Cocker et al, 2012a). These observations are also largely contrary to the effects of these compounds in tests of physical effort (e.g., Bardgett et al, 2009), although higher doses of amphetamine can reduce choice of the more effortful option in the operant task version (Floresco et al, 2008). Table 2 provides a simple overview regarding the ways in which the tasks discussed vary in terms of core structural characteristics, and variation in the neural circuitry involved.…”

“…When comparing this lack of effect with the seemingly more prominent role D 2 receptors play in decision making involving some form of punishment described earlier, it is notable that separate populations of striatal neurons expressing D 1 or D 2 receptors have been proposed to regulate different patterns of behavior. D 1 -containing cells may be more important for promoting approach behaviors, whereas activation of D 2 -expressing neurons can be aversive, suggesting their involvement in avoidance behaviors (Lobo et al, 2010;Kravitz et al, 2012). Thus, within corticostriatal circuits, D 1 versus D 2 receptors may mediate distinct forms of decision making dependent in part on whether the objective is to merely maximize rewards or avoid potentially aversive consequences.…”

“…Effortful tasks can generally be conceptualized as taxing physical or mental resources. Although human neuroimaging has started to delineate a somewhat overlapping network of frontostriatal regions implicated in both choice variants (e.g., Botvinick et al, 2009;Croxson et al, 2009;Treadway et al, 2012), it is unclear whether the allocation of cognitive and physical effort is underpinned by the same cognitive or neurobiological processes (Kool et al, 2010;Kurniawan et al, 2010), and preclinical studies may make an important contribution in this regard.…”

“…It is increasingly recognized that a range of contextual factors, including trial rate, motivational state, the "framing" of decisions (gain vs loss), and even the risk preference of probands, can also significantly impact risky choice, and likewise may be important to consider when trying to translate behavioral methods across species (Blanchard et al, 2014;Blanchard and Hayden, 2015;Cocker and Winstanley, 2015;Heilbronner and Hayden, 2016;Suzuki et al, 2016). While we have focused on rodent studies, the importance of nonhuman primate research in delineating key brain mechanisms underlying choice, such as parsing action-value versus stimulus-value computations, cannot be understated (Samejima et al, 2005;Lau and Glimcher, 2008;Morris et al, 2014). As rat decision-making research increases in complexity, its synthesis with nonhuman primate decision making research merits further consideration and may likewise highlight important areas for future research and methodological innovation (e.g., Redish, 2016).…”

“…An automated "effort-discounting" task conducted in operant chambers works on a similar principle, in which rats choose between two levers, one delivering a smaller reward after one press and the other a larger reward after a greater number of presses (1-20) that increases over blocks of trials. Advantages of this latter procedure include the ability to assess choice latencies, rates of responding (as an index of response vigor), and being able to equate the relative delay to obtain the two rewards (Floresco et al, 2008;Shafiei et al, 2012;Simon et al, 2013).…”