Effects of chronic fentanyl administration on behavioral characteristics of mice

Abstract

Background Fentanyl, a synthetic opioid categorized as a narcotic analgesic, has a 100‐ to 200‐fold stronger effect than most opioids, such as morphine. Fatal accidents due to chronic use and abuse of fentanyl are a worldwide social problem. One reason for the abuse of fentanyl is its psychostimulant effects that could induce behavioral changes. The effects of chronic fentanyl administration on behavior, however, are unclear. Methods Adult male C57BL/6J mice were chronically administered fentanyl (0.03 or 0.3 mg/kg/d i.p.), and various behaviors were assessed using a behavioral test battery. Results Mice chronically administered a high dose of fentanyl (0.3 mg/kg/d) exhibited decreased anxiety‐like behavior as assessed by the open field and elevated plus maze tests. On the other hand, interruption of fentanyl administration led to increased anxiety‐like behavior as observed in the light and dark transition test. The hot plate test revealed that chronic administration of fentanyl reduced pain sensitivity. High‐dose chronic fentanyl administration reduced the locomotor stimulatory effects of cocaine. The results, however, failed to reach the threshold for study‐wide statistical significance. Conclusion Chronic fentanyl administration induces some behavioral changes in mice. Although further studies are needed to clarify the underlying mechanisms of the behavioral effects of chronic fentanyl administration, our findings suggest that fentanyl is safe under properly controlled conditions.

Sex‐dependent effects of anHnrnph1mutation on fentanyl addiction‐relevant behaviors but not antinociception in mice

“…The lack of tolerance and subtle physical dependence we observed is unlikely to be explained by insufficient dosing as 0.8 mg/kg of systemic fentanyl is considered quite high of a dose. Behavioral signs of fentanyl dependence (e.g., changes in elevated plus maze behavior) have been observed following repeated fentanyl dosing with 0.3 mg/kg in C57BL/6J mice but with the exception that a longer treatment regimen of two to 4 weeks was used 75 . Thus, a longer treatment regimen with 0.8 mg/kg fentanyl could induce more reliable opioid tolerance and additional behavioral signs of opioid withdrawal.…”

“…Behavioral signs of fentanyl dependence (e.g., changes in elevated plus maze behavior) have been observed following repeated fentanyl dosing with 0.3 mg/kg in C57BL/6J mice but with the exception that a longer treatment regimen of two to 4 weeks was used. 75 Thus, a longer treatment regimen with 0. To summarize, we found complex, and sometimes sex-dependent effects on fentanyl-induced locomotor activity, sensitization, reward, and reinforcement efficacy in Hn1+/− mice.…”

Fentanyl-induced antinociception, reward, reinforcement, and withdrawal inHnrnph1mutant mice

“…The subtle tolerance is unlikely to be explained by insufficient fentanyl dosing as 0.8 mg/kg is considered a high dose that induces clear, behavioral signs of intoxicationeven one-half of this fentanyl dose (0.4 mg/kg) induces severe respiratory depression in C57BL/6J mice (Fechtner et al 2015). Behavioral signs of fentanyl dependence (e.g., changes in elevated plus maze behavior) have been observed following repeated fentanyl dosing with 0.3 mg/kg in C57BL/6J mice but with the exception that a longer treatment regimen of two to four weeks was used (Fujii et al 2019). Thus, a longer treatment regimen with 0.8 mg/kg fentanyl could induce more reliable opioid tolerance.…”

Oxycodone decreases anxiety-like behavior in the elevated plus-maze test in male and female rats

“…-ol]-enkephalin) does not affect anxiety-like behavior in the elevated plus-maze test in rats (Alexeeva et al, 2012); however, there is evidence that treatment with the opioid drugs morphine and fentanyl decreases anxiety-like behavior (Fujii et al, 2019;Koks et al, 1999;Rezayof et al, 2009). The goal of the present study was to investigate the effects of acute oxycodone administration on anxiety-like behavior and locomotor activity in adult male and female rats.…”