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

Abstract

Individuals with opioid use disorder (OUD) exhibit impaired decisionmaking and elevated risk-taking behavior. In contrast to the effects of natural and semi-synthetic opioids, however, the impact of synthetic opioids on decisionmaking is still unknown. The objective of the current study was to determine how chronic exposure to the synthetic opioid fentanyl alters risk-based decisionmaking in adult male rats. 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. 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 risktaking was driven by enhanced sensitivity to the large rewards and diminished sensitivity to punishment. The fentanyl-induced elevation in risktaking was not accompanied by alterations in food motivation or shock reactivity or impairments in behavioral flexibility. Results from the current study reveal that the synthetic opioid fentanyl leads to long-lasting increases in risktaking in male rats. Future experiments will extend this work to females and identify neural mechanisms that underlie these drug-induced changes in risktaking.