Age-Related Changes in Risky Decision Making and Associated Neural Circuitry in a Rat Model.

Altered decision making at advanced ages can have a significant impact on an individual's quality of life and the ability to maintain personal independence. Relative to young adults, older adults make less impulsive and less risky choices; although these changes in decision making could be considered beneficial, they can also lead to choices with potentially negative consequences (e.g., avoidance of medical procedures). Rodent models of decision making have been invaluable for dissecting cognitive and neurobiological mechanisms that contribute to age-related changes in decision making, but they have predominantly used costs related to timing or probability of reward delivery and have not considered other equally important costs, such as the risk of adverse consequences. The current study therefore used a rat model of decision making involving risk of explicit punishment to examine age-related changes in this form of choice behavior in male rats, and to identify potential cognitive and neurobiological mechanisms that contribute to these changes. Relative to young rats, aged rats displayed greater risk aversion, which was not attributable to reduced motivation for food, changes in shock sensitivity, or impaired cognitive flexibility. Functional MRI analyses revealed that, overall, functional connectivity was greater in aged rats compared with young rats, particularly among brain regions implicated in risky decision making such as basolateral amygdala, orbitofrontal cortex, and ventral tegmental area. Collectively, these findings are consistent with greater risk aversion found in older humans, and reveal age-related changes in brain connectivity.

Distinct relationships between risky decision making and cocaine self-administration under short- and long-access conditions.

Substance use is strongly associated with impaired decision making, with cocaine use particularly linked to elevated risky and impulsive choice. It is not clear, however, whether such maladaptive decision making is a consequence of cocaine use or instead precedes and predisposes individuals to cocaine use. The current study was designed to specifically address the latter possibility with respect to risky choice in both male and female rats. Rats were first trained in a "Risky Decision-making Task" (RDT), in which they made discrete choices between a small, "safe" food reward and a large, "risky" food reward accompanied by increasing probabilities of mild footshock punishment. After reaching stable performance, rats underwent jugular catheter surgery followed by either short-access cocaine self-administration sessions (2 h, 0.5 mg/kg/infusion) for 5 days or long-access cocaine self-administration sessions (6 h, 0.5 mg/kg/infusion) for 14 days. Under short-access conditions, there was no relationship between risk preference and changes in cocaine intake over time, but greater risk aversion in females predicted greater overall cocaine intake. Under long-access conditions, heightened risk taking predicted greater escalation of cocaine intake over the course of self-administration, supporting the notion that pre-existing risk-taking behavior predicts cocaine intake. Collectively, results from these experiments have implications for understanding and identifying pre-existing vulnerabilities to substance use, which may lead to strategies to prevent development of substance use disorders.