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

Wheeler, Alexa-Rae; Truckenbrod, Leah M.; Cooper, Emily M.; Betzhold, Sara M.; Setlow, Barry; Orsini, Caitlin A.

doi:10.1007/s00213-023-06447-y

Cited by 5 publications

(5 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The current study builds upon previous findings and demonstrates that 2 hours of access to 2.5 µg/kg/infusion of fentanyl over 14 days is sufficient to establish escalation of fentanyl intake and result in withdrawal symptoms in mice. Previous literature has investigated rodent models of opioid dependence, including morphine (47)(48)(49), oxycodone (10,12,50,51), heroin (6,(52)(53)(54), remifentanil (34,(55)(56)(57)(58), and fentanyl (24,33,36,38,(59)(60)(61)(62)(63)(64)(65)(66), using various routes of administration, with the majority of studies done in rats. IVSA of fentanyl has been widely studied in rats (24,25,(59)(60)(61)(62)(67)(68)(69)(70)(71), with findings demonstrating mixed results on the development of dependence and withdrawal signs.…”

Section: Discussionmentioning

confidence: 99%

“…Previous literature has investigated rodent models of opioid dependence, including morphine (47)(48)(49), oxycodone (10,12,50,51), heroin (6,(52)(53)(54), remifentanil (34,(55)(56)(57)(58), and fentanyl (24,33,36,38,(59)(60)(61)(62)(63)(64)(65)(66), using various routes of administration, with the majority of studies done in rats. IVSA of fentanyl has been widely studied in rats (24,25,(59)(60)(61)(62)(67)(68)(69)(70)(71), with findings demonstrating mixed results on the development of dependence and withdrawal signs. One previous study reported that rats undergoing 14 days IVSA of fentanyl for 6 hours per day maintained a consistent rate of self-administration (62).…”

Section: Discussionmentioning

confidence: 99%

“…IVSA of fentanyl has been widely studied in rats (24,25,(59)(60)(61)(62)(67)(68)(69)(70)(71), with findings demonstrating mixed results on the development of dependence and withdrawal signs. One previous study reported that rats undergoing 14 days IVSA of fentanyl for 6 hours per day maintained a consistent rate of self-administration (62). Another study found that rats self-administering fentanyl for 3 hours per day over 10 days exhibited a trend towards increasing reward-associated lever presses (59).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Escalation of intravenous fentanyl self-administration and assessment of withdrawal behavior in male and female mice

Chen,

Xiao,

Kimbrough

2024

Preprint

View full text Add to dashboard Cite

BackgroundThe rise in overdose deaths from synthetic opioids, especially fentanyl, necessitates the development of preclinical models to study fentanyl use disorder (FUD). While there has been progress with rodent models, additional translationally relevant models are needed to examine excessive fentanyl intake and withdrawal symptoms.MethodsThe study performed intravenous self-administration (IVSA) of fentanyl in male and female C57BL/6J mice for 14 days. Mechanical pain sensitivity during withdrawal was assessed using the von Frey test. Anxiety-like behavior was evaluated via the open field test one-week into abstinence and incubation of craving for fentanyl was assessed four weeks into abstinence.ResultsBoth male and female mice demonstrated a significant escalation in fentanyl intake over the 14 days of self-administration, with significant front-loading observed in the final days of self-administration. Increased mechanical pain sensitivity was present from 36- to 48-hour into withdrawal and increased anxiety-like behavior was found 1 week into abstinence. Four weeks into abstinence, mice showed significantly higher active lever pressing than the final self-administration session prior to abstinence.ConclusionsThe study establishes a translationally relevant mouse model of IVSA of fentanyl, effectively encapsulating critical aspects of FUD, including escalation of drug intake, front-loading behavior, withdrawal symptoms, and prolonged craving for drug into abstinence. This model offers a robust basis for further exploration into behavioral and neurobiological mechanisms involved in fentanyl dependence and potential therapeutic strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Escalation of intravenous fentanyl self-administration and assessment of withdrawal behavior in male and female mice

Chen,

Xiao,

Kimbrough

2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Previous work shows that preference for the large, risky reward in the RDT is associated with sensitivity to drugs of abuse and drug self-administration (Gabriel et al, 2019;Mitchell et al, 2014;Wheeler et al, 2023). Using this task, here we evaluated the effects of acute systemic administration of OT and an oxytocin antagonist (L-368,899 hydrochloride) on female and male rats' behavior.…”

Section: Introductionmentioning

confidence: 99%

“…To examine potential contributions of OT to decision making under risk of explicit punishment, we used a risky decision-making task (RDT), in which rats choose between a small, “safe” food reward and a large, “risky” food reward that is accompanied by varying probabilities of mild footshock (Orsini et al, 2019; Simon et al, 2009). Previous work shows that preference for the large, risky reward in the RDT is associated with sensitivity to drugs of abuse and drug self-administration (Gabriel et al, 2019; Mitchell et al, 2014; Wheeler et al, 2023). Using this task, here we evaluated the effects of acute systemic administration of OT and an oxytocin antagonist (L-368,899 hydrochloride) on female and male rats’ behavior.…”

Section: Introductionmentioning

confidence: 99%

Effects of systemic oxytocin receptor activation and blockade on risky decision making in female and male rats

Faraji,

Viera-Resto,

Berrios

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

The neuropeptide oxytocin is traditionally known for its roles in parturition, lactation, and social behavior. Other data, however, show that oxytocin can modulate behaviors outside of these contexts, including drug self-administration and some aspects of cost-benefit decision making. Here we used a pharmacological approach to investigate the contributions of oxytocin signaling to decision making under risk of explicit punishment. Female and male Long-Evans rats were trained on a risky decision-making task in which they chose between a small, safe food reward and a large, risky food reward that was accompanied by varying probabilities of mild footshock. Once stable choice behavior emerged, rats were tested in the task following acute intraperitoneal injections of oxytocin or the oxytocin receptor antagonist L-368,899. Neither drug affected task performance in males. In females, however, both oxytocin and L-368,899 caused a dose-dependent reduction in preference for large risky reward. Control experiments showed that these effects could not be accounted for by alterations in food motivation or shock sensitivity. Together, these results reveal a sex-dependent effect of oxytocin signaling on risky decision making in rats.

show abstract