The contribution of medium spiny neuron subtypes in the nucleus accumbens core to compulsive-like ethanol drinking

Sneddon, Elizabeth A.; Schuh, Kristen M.; Frankel, John W.; Radke, Anna K.

doi:10.1016/j.neuropharm.2021.108497

Cited by 19 publications

(20 citation statements)

References 38 publications

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“…For example, we reported that female mice drink more EtOH than males using a limited‐access “drinking in the dark” paradigm (Sneddon et al., 2019). In a recent follow‐up study (Sneddon, Schuh, Frankel, & Radke, 2021), we also observed greater consumption in females versus males (i.e., a main effect of sex), but the two groups responded equally to treatment (i.e., no sex × treatment interaction). In such a case, it is acceptable to combine the data and analyze males and females as one experimental group (see the section on data analysis below).…”

Section: Considerations For Experimental Design and Implementationsupporting

confidence: 65%

Studying Sex Differences in Rodent Models of Addictive Behavior

2021

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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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Section: Considerations For Experimental Design and Implementationsupporting

confidence: 65%

Studying Sex Differences in Rodent Models of Addictive Behavior

2021

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“…The Radke lab recently evaluated the contribution of NAcb core medium spiny neuron (MSN) subtypes and dopamine receptors (D 1 -like and D 2 -like receptors) to binge and compulsion-like alcohol drinking using two-bottle choice DID in male and female C57 mice [144]. We found that binge alcohol drinking (15%) on quinine-free sessions was not affected by selective chemogenetic inhibition of D 1 -receptor expressing "direct" pathway neurons (D 1 -neurons) or D 2 -receptor expressing "indirect" pathway neurons (D 2 -neurons).…”

Section: Nacb Core In Binge and Compulsion-like Alcohol Drinkingmentioning

confidence: 99%

“…We next looked at regulation of quinine-adulterated DID alcohol intake by NAcb core cells [144]. Here, chemogenetic inhibition of NAcb core neurons (i.e., without targeting a particular cell type) reduced compulsion-like drinking similarly in females and males, while targeted inhibition of D 1 -neurons or D 2 -neurons was ineffective (similar to alcohol-only DID intake above).…”

Section: Nacb Core In Binge and Compulsion-like Alcohol Drinkingmentioning

confidence: 99%

Recent Perspectives on Sex Differences in Compulsion-Like and Binge Alcohol Drinking

Radke

Sneddon

Frasier

et al. 2021

IJMS

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Alcohol use disorder remains a substantial social, health, and economic problem and problem drinking levels in women have been increasing in recent years. Understanding whether and how the underlying mechanisms that drive drinking vary by sex is critical and could provide novel, more targeted therapeutic treatments. Here, we examine recent results from our laboratories and others which we believe provide useful insights into similarities and differences in alcohol drinking patterns across the sexes. Findings for binge intake and aversion-resistant, compulsion-like alcohol drinking are considered, since both are likely significant contributors to alcohol problems in humans. We also describe studies regarding mechanisms that may underlie sex differences in maladaptive alcohol drinking, with some focus on the importance of nucleus accumbens (NAcb) core and shell regions, several receptor types (dopamine, orexin, AMPA-type glutamate), and possible contributions of sex hormones. Finally, we discuss how stressors such as early life stress and anxiety-like states may interact with sex differences to contribute to alcohol drinking. Together, these findings underscore the importance and critical relevance of studying female and male mechanisms for alcohol and co-morbid conditions to gain a true and clinically useful understanding of addiction and neuropsychiatric mechanisms and treatment.

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“…For example, pharmacological inactivations of the rat NAcCore produce a generalized reduction in the vigor of behaviors associated with reward (sucrose) seeking or punishment avoidance, without directly affecting risk seeking per se (Floresco et al, 2018;Piantadosi et al, 2017Piantadosi et al, , 2018). Yet, in rodent models of quinine-resistant alcohol drinking, both N-methyl-D-aspartate (NMDA)-receptor modulation and chemogenetic inhibition of medium spiny neurons in the NAcCore can selectively reduce punished drinking, without generally affecting motivation (Seif et al, 2013(Seif et al, , 2015Sneddon et al, 2021). This pattern of results suggests that, depending on the nature of the reward (e.g., drug vs. natural reinforcer) or the type of functional manipulation, the NAcCore can be shown to promote or suppress reward-seeking behaviors.…”

Section: N Ucleus Accumb En S: Utilizing Dopamine To Adj Us T Ris K Y B Ehavi Ormentioning

confidence: 99%

Advances in understanding meso‐cortico‐limbic‐striatal systems mediating risky reward seeking

Piantadosi

Halladay

Radke

et al. 2021

Journal of Neurochemistry

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Nearly all choices carry some degree of risk, defined as the possibility that an undesirable outcome might arise from a choice and subsequent course of action (Yates & Stone, 1992). Typically, the risk of an aversive event occurring following a particular action biases future behavior toward other, safer actions. However, this adaptive flexibility is compromised in a variety of neuropsychiatric conditions. Of particular note, alcohol use disorders (AUDs), substance use disorders (SUDs), and behavioral addictions are characterized by

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The contribution of medium spiny neuron subtypes in the nucleus accumbens core to compulsive-like ethanol drinking

Cited by 19 publications

References 38 publications

Studying Sex Differences in Rodent Models of Addictive Behavior

Studying Sex Differences in Rodent Models of Addictive Behavior

Recent Perspectives on Sex Differences in Compulsion-Like and Binge Alcohol Drinking

Advances in understanding meso‐cortico‐limbic‐striatal systems mediating risky reward seeking

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