Aversion-resistant fentanyl self-administration in mice

Monroe, Sean C; Radke, Anna K.

doi:10.1007/s00213-020-05722-6

Cited by 34 publications

(44 citation statements)

References 68 publications

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“…PTSD, depression) (Bangasser et al, 2019). While we do not see striking sex-differences in our behavioral readout of susceptibility in mice, the persistently increased opioid consumption in our female mice mirrors that of humans and of other recent mouse work (Monroe and Radke, 2020). When we compare mice from our modified forced/choice model (Shaham et al, 1992) to mice that had free-choice throughout the entire procedure, stressed males do not appear different from unstressed males.…”

Section: Discussionsupporting

confidence: 51%

Chronic Physical and Vicarious Psychosocial Stress Alter Fentanyl Consumption and Nucleus Accumbens Rho GTPases in Male and Female C57BL/6 Mice

Franco

Wulff

Lobo

et al. 2021

Preprint

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Chronic stress can increase the risk of developing a substance use disorder in vulnerable individuals. Numerous models have been developed to probe the underlying neurobiological mechanisms, however most prior work has been restricted to male rodents, conducted only in rats, or introduces physical injury that can complicate opioid studies. Here we sought to establish how chronic psychosocial stress influences fentanyl consumption in male and female C57BL/6 mice. We used chronic social defeat stress (CSDS), or the modified vicarious chronic witness defeat stress (CWDS), and used social interaction to stratify mice as stress-susceptible or resilient. We then subjected mice to a 15 day fentanyl drinking paradigm in the home cage that consisted of alternating forced and choice periods with increasing fentanyl concentrations. Male mice susceptible to either CWDS or CSDS consumed more fentanyl relative to unstressed mice, and exhibited increased preference for fentanyl. CWDS-susceptible female mice did not differ from unstressed mice during the forced periods, but showed increased preference for fentanyl. We also found decreased expression of nucleus accumbens Rho GTPases in male, but not female mice following stress and fentanyl drinking. We also compare fentanyl drinking behavior in mice that had free access to plain water throughout. Our results indicate that stress-sensitized fentanyl consumption is dependent on both sex and behavioral outcomes to stress.

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Section: Discussionsupporting

confidence: 51%

Chronic Physical and Vicarious Psychosocial Stress Alter Fentanyl Consumption and Nucleus Accumbens Rho GTPases in Male and Female C57BL/6 Mice

Franco

Wulff

Lobo

et al. 2021

Preprint

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“…In the operant chamber, female mice demonstrated continued responding for EtOH mixed with quinine at quinine concentrations that reduced responding in males (Sneddon et al, 2020). Greater aversion resistance in female versus male mice has also been demonstrated for oral fentanyl consumption in the home cage, but not the operant chamber (Monroe & Radke, 2020). It is important to note that not all studies have found sex differences in aversion resistance (Bauer, McVey, & Boehm, 2021;DeBaker, Moen, Robinson, Wickman, & Lee, 2020;Sneddon et al, 2019), further demonstrating the importance of the behavioral paradigm in revealing female vulnerability to addictive behavior.…”

Section: Sex Differences In Addictive Behaviorsmentioning

confidence: 98%

Studying Sex Differences in Rodent Models of Addictive Behavior

2021

Self Cite

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Animal models of addictive behaviors are useful for uncovering neural mechanisms involved in the development of dependence and for identifying risk factors for drug abuse. One such risk factor is biological sex, which strongly moderates drug self‐administration behavior in rodents. Female rodents are more likely to acquire drug self‐administration behaviors, consume higher amounts of drug, and reinstate drug‐seeking behavior more readily. Despite this female vulnerability, preclinical addiction research has largely been done in male animals. The study of sex differences in rodent models of addictive behavior is increasing, however, as more investigators are choosing to include both male and female animals in experiments. This commentary is meant to serve as an introductory guide for preclinical investigators new to the study of sex differences in addiction. We provide an overview of self‐administration models, a broad view of female versus male self‐administration behaviors, and suggestions for study design and implementation. Inclusion of female subjects in preclinical addiction research is timely, as problem drug and alcohol use in women is increasing. With proper attention, design, and analysis, the study of sex differences in addiction has the potential to uncover novel neural mechanisms and lead to greater translational success for addiction research. © 2021 Wiley Periodicals LLC

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“…In related punishment-based models, reward seeking actions also result in the delivery of noxious or otherwise aversive stimulus, such as footshock, or a bitter taste. A history of escalated use of several drugs, including cocaine, alcohol, and opiates promotes punishment resistance ( Vanderschuren and Everitt, 2004 ; Pelloux et al, 2007 ; Marchant et al, 2013 ; Hopf and Lesscher, 2014 ; Blackwood et al, 2020 ; Monroe and Radke, 2021 ; Domi et al, 2021 ). Notably, these tasks are particularly useful for assessing individual differences in addiction-like behavior, as only a subset of animal subjects will persist in drug seeking in the face of high cost ( Shaham et al, 2003 ; Everitt and Robbins, 2005 ; Cooper et al, 2007 ; Vanderschuren et al, 2017 ; Giuliano et al, 2018 ).…”

Section: Category III – Risky Substance Usementioning

confidence: 99%

Dopamine Circuit Mechanisms of Addiction-Like Behaviors

Poisson

Engel

Saunders

2021

Front. Neural Circuits

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Addiction is a complex disease that impacts millions of people around the world. Clinically, addiction is formalized as substance use disorder (SUD), with three primary symptom categories: exaggerated substance use, social or lifestyle impairment, and risky substance use. Considerable efforts have been made to model features of these criteria in non-human animal research subjects, for insight into the underlying neurobiological mechanisms. Here we review evidence from rodent models of SUD-inspired criteria, focusing on the role of the striatal dopamine system. We identify distinct mesostriatal and nigrostriatal dopamine circuit functions in behavioral outcomes that are relevant to addictions and SUDs. This work suggests that striatal dopamine is essential for not only positive symptom features of SUDs, such as elevated intake and craving, but also for impairments in decision making that underlie compulsive behavior, reduced sociality, and risk taking. Understanding the functional heterogeneity of the dopamine system and related networks can offer insight into this complex symptomatology and may lead to more targeted treatments.

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Aversion-resistant fentanyl self-administration in mice

Cited by 34 publications

References 68 publications

Chronic Physical and Vicarious Psychosocial Stress Alter Fentanyl Consumption and Nucleus Accumbens Rho GTPases in Male and Female C57BL/6 Mice

Chronic Physical and Vicarious Psychosocial Stress Alter Fentanyl Consumption and Nucleus Accumbens Rho GTPases in Male and Female C57BL/6 Mice

Studying Sex Differences in Rodent Models of Addictive Behavior

Dopamine Circuit Mechanisms of Addiction-Like Behaviors

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