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

Psychopharmacology (Berl). 2023 Dec;240(12):2529-2544. doi: 10.1007/s00213-023-06447-y. Epub 2023 Aug 23.

Abstract

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.

Keywords: Decision Making; Fentanyl; Flexibility; Opioid; Rats; Reward; Risk taking; Self-administration.

MeSH terms

  • Analgesics, Opioid / pharmacology
  • Animals
  • Decision Making*
  • Female
  • Fentanyl* / pharmacology
  • Male
  • Rats
  • Rats, Long-Evans
  • Reward
  • Risk-Taking
  • Sucrose / pharmacology

Substances

  • Fentanyl
  • Analgesics, Opioid
  • Sucrose