Chronic inflammatory pain promotes place preference for fentanyl in male rats but does not change fentanyl self-administration in male and female rats

Barattini, Angela E.; Montanari, Christian; Edwards, Kimberly N.; Edwards, Scott; Gilpin, Nicholas W.; Pahng, Amanda R.

doi:10.1016/j.neuropharm.2023.109512

Cited by 11 publications

(3 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Particularly, conditioning with 10 mg/kg of morphine led to CPP and risk-taking behavior during conflict in male rats, but this dose was insufficient to produce either of these behaviors in female rats. Previous studies have reported similar levels of opioid CPP in male and female rodents [73–76], suggesting no significant sex differences in the rewarding effects of opioids. Conversely, other studies have reported enhanced opioid CPP in female vs. male rats, indicating greater sensitivity to the rewarding properties of opioids in females [77–83].…”

Section: Discussionmentioning

confidence: 77%

Neural signatures of opioid-induced risk-taking behavior in the prelimbic prefrontal cortex

Quave,

Vasquez,

Aquino-Miranda

et al. 2024

Preprint

View full text Add to dashboard Cite

Opioid use disorder occurs alongside impaired risk-related decision-making, but the underlying neural correlates are unclear. We developed a novel approach-avoidance conflict model using a modified conditioned place preference paradigm to study neural signals of risky opioid seeking in the prefrontal cortex, a region implicated in executive decision making. Upon establishment of morphine conditioned place preference, rats underwent a subsequent conflict test in which fear-inducing cat odor was introduced in the previously drug-paired side of the apparatus. While the saline control group avoided the cat odor side, the morphine group maintained preference for the paired side despite the presence of cat odor. K-means clustering identified two subsets of morphine-treated rats that exhibited either persistent drug seeking (Risk-Takers) or increased avoidance (Risk-Avoiders) during conflict. Single-unit recordings from the prelimbic cortex (PL) revealed decreased neuronal firing rates upon acute morphine exposure in both Risk-Takers and Risk-Avoiders, but this firing rate suppression was absent after repeated administration. Risk-Avoiders also displayed distinct post-morphine excitation in PL which persisted across conditioning. During the preference test, subpopulations of PL neurons in all groups were either excited or inhibited when rats entered the paired side. Interestingly, while this inhibitory signal was lost during the subsequent conflict test in both saline and Risk-Avoider groups, these inhibitory responses persisted in Risk-Takers. Our results suggest that loss of PL inhibition after opioid conditioning is associated with the formation of contextual reward memory. Furthermore, persistent PL inhibitory signaling in the drug associated context during conflict may underlie increased risk taking following opioid exposure.

show abstract

Section: Discussionmentioning

confidence: 77%

Neural signatures of opioid-induced risk-taking behavior in the prelimbic prefrontal cortex

Quave,

Vasquez,

Aquino-Miranda

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…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%

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

“…The CPP paradigm is a model used to understand the mechanism of various addictive drugs such as psychostimulants. [41][42][43][44], cannabinoids [45,46], and opioids [47]. This model is based on the positive association hypothesis involving a specific context or stimulus during drug administration.…”

Section: Discussionmentioning

confidence: 99%

The (–)-Borneol Effect on Addiction/Abstinence by Morphine in Mice

Amaral

Viana

Osório

et al. 2023

DDC

View full text Add to dashboard Cite

Opioids such as morphine are the first choice in acute and chronic pain treatment. However, they lead to addiction. Several studies have searched (i) to find a molecule that can replace morphine use or (ii) to reduce its adverse effects. This work aimed to evaluate whether (–)-Borneol [(–)-BOR], a bicyclic monoterpene, in doses of 25, 50, and 100 mg/kg (i.p.), has an antiaddictive effect on morphine (5 mg/kg, i.p.) and reduces its withdrawal symptoms precipitated by naloxone (8 mg/kg, i.p.) in Swiss mice. Furthermore, the (–)-BOR genotoxic potential was also investigated by the comet assay. The antiaddictive effect of (–)-BOR was evaluated by the conditioned preference place (CPP). The CPP was induced by morphine administration during the conditioning phase. The effects of (–)-BOR on the rewarding characteristics of morphine were tested in mice with the administration of (–)-BOR, naloxone, or vehicle (NaCl 0.9%), 30 min before morphine. This work also investigated the (–)-BOR effect on morphine withdrawal symptoms precipitated by naloxone. Morphine withdrawal symptoms were induced by administering morphine twice daily for 5 days, precipitated by naloxone administration on the sixth day. The effect of (–)-BOR on reducing morphine withdrawal symptoms was evaluated in mice that received (–)-BOR before daily morphine administration. Finally, the comet assay was performed to assess the DNA damage degree caused by the (–)-BOR (100 mg/kg, i.p.) administration. The comet assay was performed on peripheral blood taken from the tail of each animal. Cyclophosphamide (50 mg/kg, i.p.) was used to induce DNA damage. After starting the protocol, analyses were performed for 4 h (acute effect) and 24 h (repair effect). The (–)-BOR (100 mg/kg, i.p.) significantly attenuated (*** p < 0.001) the acquisition of morphine-induced CPP and reduced only the jumping behavior in the morphine withdrawal model. The best-studied dose was 100 mg/kg, being evaluated, then, in the comet assay. (–)-BOR at 100 mg/kg did not show the genotoxic effect when compared with the cyclophosphamide group (CYCLO, 50 mg/kg, i.p.) after 4 h or 24 h, a period that corresponded to the repair time of DNA fragmentation. The study showed that (–)-BOR attenuated the acquisition of CPP by morphine and made opioid withdrawal milder. In the comet assay, although (–)-BOR caused DNA damage, this damage was significantly less than the damage by CYCLO, at either 4 h or 24 h after the treatments.

show abstract

Chronic inflammatory pain promotes place preference for fentanyl in male rats but does not change fentanyl self-administration in male and female rats

Cited by 11 publications

References 73 publications

Neural signatures of opioid-induced risk-taking behavior in the prelimbic prefrontal cortex

Neural signatures of opioid-induced risk-taking behavior in the prelimbic prefrontal cortex

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

The (–)-Borneol Effect on Addiction/Abstinence by Morphine in Mice

Contact Info

Product

Resources

About