Cocaine intake correlates with risk-taking behavior and affects estrous cycling in female Sprague-Dawley rats.

Navigating complex decisions and considering their relative risks and rewards is an important cognitive ability necessary for survival. However, use of and dependence on illicit drugs can result in long-lasting changes to this risk/reward calculus in individuals with substance use disorder. Recent work has shown that chronic exposure to cocaine causes long-lasting increases in risk taking in male and female rats, but there are still significant gaps in our understanding of the relationship between cocaine use and changes in risk taking. For example, it is unclear whether the magnitude of cocaine intake dictates the extent to which risk taking is altered. To address this, male and female Sprague-Dawley rats underwent cocaine (or sucrose) self-administration and, following a period of abstinence, were trained and tested in a rodent model of risky decision making. In this behavioral task, rats made discrete-trial choices between a lever associated with a small food reward (i.e., "safe" option) and a lever associated with a larger food reward accompanied by a variable risk of footshock delivery (i.e., "risky" option). Surprisingly, and in contrast to prior work in Long-Evans rats, there were no effects of cocaine self-administration on choice of the large, risky reward (i.e., risk taking) during abstinence in males or females. There was, however, a significant relationship between cocaine intake and risk taking in female rats, with greater intake associated with greater preference for the large, risky reward. Relative to their sucrose counterparts, female rats in the cocaine group also exhibited irregular estrous cycles, characterized by prolonged estrus and/or diestrus phases. Collectively, these data suggest that there may be strain differences in the effects of cocaine on risk taking and highlight the impact that chronic cocaine exposure has on hormonal cyclicity in females. Future work will focus on understanding the neural mechanisms underlying cocaine's intake-dependent effects on risk taking in females, and whether this is directly related to cocaine-induced alterations in neuroendocrine function.

Effects of fentanyl self-administration on risk-taking behavior in male rats.

RATIONALE: Individuals with opioid use disorder (OUD) exhibit impaired decision making and elevated risk-taking behavior. In contrast to the effects of natural and semi-synthetic opioids, however, the impact of synthetic opioids on decision making is still unknown. OBJECTIVES: The objective of the current study was to determine how chronic exposure to the synthetic opioid fentanyl alters risk-based decision making in adult male rats. METHODS: Male rats underwent 14 days of intravenous fentanyl or oral sucrose self-administration. After 3 weeks of abstinence, rats were tested in a decision-making task in which they chose between a small, safe food reward and a large food reward accompanied by variable risk of footshock punishment. Following testing in the decision-making task, rats were tested in control assays that assessed willingness to work for food and shock reactivity. Lastly, rats were tested on a probabilistic reversal learning task to evaluate enduring effects of fentanyl on behavioral flexibility. RESULTS: Relative to rats in the sucrose group, rats in the fentanyl group displayed greater choice of the large, risky reward (risk taking), an effect that was present as long as 7 weeks into abstinence. This increased risk taking was driven by enhanced sensitivity to the large rewards and diminished sensitivity to punishment. The fentanyl-induced elevation in risk taking was not accompanied by alterations in food motivation or shock reactivity or impairments in behavioral flexibility. CONCLUSIONS: Results from the current study reveal that the synthetic opioid fentanyl leads to long-lasting increases in risk taking in male rats. Future experiments will extend this work to females and identify neural mechanisms that underlie these drug-induced changes in risk taking.

Cognitive mechanisms underlying decision making involving risk of explicit punishment in male and female rats.

Individuals engage in the process of risk-based decision making on a daily basis to navigate various aspects of life. There are, however, individual differences in this form of decision making, with some individuals exhibiting preference for riskier choices (risk taking) and others exhibiting preference for safer choices (risk aversion). Recent work has shown that extremes in risk taking (e.g., excessive risk taking or risk aversion) are not only cognitive features of neuropsychiatric diseases, but may in fact predispose individuals to the development of such diseases. To better understand individual differences in risk taking, and thus the mechanisms by which they confer disease vulnerability, the current study investigated the cognitive contributions to risk taking in both males and females. Rats were first behaviorally characterized in a decision-making task involving risk of footshock punishment and then tested on a battery of cognitive behavioral assays. Individual variability in risk taking was compared with performance on these tasks. Consistent with prior work, females were more risk averse than males. With the exception of the Set-shifting Task, there were no sex differences in performance on other cognitive assays. There were, however, sex-dependent associations between risk taking and specific cognitive measures. Greater risk taking was associated with better cognitive flexibility in males whereas greater risk aversion was associated with better working memory in females. Collectively, these findings reveal that distinct cognitive mechanisms are associated with risk taking in males and females, which may account for sex differences in this form of decision making.