Experimental Models of Alcohol Use Disorder and Their Application for Pathophysiological Investigations

Vierkant, Valerie; Xie, Xueyi; Wang, Jun

doi:10.1002/cpz1.831

Cited by 3 publications

(1 citation statement)

References 28 publications

(24 reference statements)

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“…Alcohol vapor is a widely used tool in animal models to induce AUD-related phenotypes from invertebrates to mammals, including eliciting an acute tolerance response in Drosophila and rodents [ 48 , 49 ]. Especially in rodent models, alcohol vapor inhalation stands as a frequently employed method, reliably inducing forced exposure and establishing physical alcohol dependence, thereby influencing subsequent alcohol consumption behavior [ 50 , 51 ]. This method offers meticulous control over dosage, duration, and temporal alcohol exposure patterns throughout the experimental procedure.…”

Section: Discussionmentioning

confidence: 99%

JNK Signaling Positively Regulates Acute Ethanol Tolerance in C. elegans

Jee,

Batsaikhan

2024

IJMS

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Alcohol use disorder (AUD) is a chronic neurobehavioral condition characterized by a cycle of tolerance development, increased consumption, and reinstated craving and seeking behaviors during withdrawal. Understanding the intricate mechanisms of AUD necessitates reliable animal models reflecting its key features. Caenorhabditis elegans (C. elegans), with its conserved nervous system and genetic tractability, has emerged as a valuable model organism to study AUD. Here, we employ an ethanol vapor exposure model in Caenorhabditis elegans, recapitulating AUD features while maintaining high-throughput scalability. We demonstrate that ethanol vapor exposure induces intoxication-like behaviors, acute tolerance, and ethanol preference, akin to mammalian AUD traits. Leveraging this model, we elucidate the conserved role of c-jun N-terminal kinase (JNK) signaling in mediating acute ethanol tolerance. Mutants lacking JNK signaling components exhibit impaired tolerance development, highlighting JNK’s positive regulation. Furthermore, we detect ethanol-induced JNK activation in C. elegans. Our findings underscore the utility of C. elegans with ethanol vapor exposure for studying AUD and offer novel insights into the molecular mechanisms underlying acute ethanol tolerance through JNK signaling.

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Section: Discussionmentioning

confidence: 99%

JNK Signaling Positively Regulates Acute Ethanol Tolerance in C. elegans

Jee,

Batsaikhan

2024

IJMS

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Traumatic Brain Injury Exacerbates Alcohol Consumption and Neuroinflammation with Decline in Cognition and Cholinergic Activity

Gangal,

Iannucci,

Huang

et al. 2024

Preprint

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Traumatic brain injury (TBI) is a global health challenge, responsible for 30% of injury-related deaths and significantly contributing to disability. Annually, over 50 million TBIs occur worldwide, with most adult patients at emergency departments showing alcohol in their system. TBI is also a known risk factor for alcohol abuse, yet its interaction with alcohol consumption remains poorly understood. In this study, we demonstrate that the fluid percussion injury (FPI) model of TBI in mice significantly increases alcohol consumption and impairs cognitive function. At cellular levels, FPI markedly reduced the number and activity of striatal cholinergic interneurons (CINs) while increasing microglial cells. Notably, depleting microglial cells provided neuroprotection, mitigating cholinergic loss and enhancing cholinergic activity. These findings suggest that TBI may promote alcohol consumption and impair cognitive abilities through microglia activation and consequently reduced cholinergic function. Our research provides critical insights into the mechanisms linking TBI with increased alcohol use and cognitive deficits, potentially guiding future therapeutic strategies.

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Optogenetic inhibition of light‐captured alcohol‐taking striatal engrams facilitates extinction and suppresses reinstatement

Vierkant,

Xie,

Huang

et al. 2024

Alcohol, Clinical and Experimental Research

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BackgroundAlcohol use disorder (AUD) is a complex condition, and it remains unclear which specific neuronal substrates mediate alcohol‐seeking and ‐taking behaviors. Engram cells and their related ensembles, which encode learning and memory, may play a role in this process. We aimed to assess the precise neural substrates underlying alcohol‐seeking and ‐taking behaviors and determine how they may affect one another.MethodsUsing FLiCRE (Fast Light and Calcium‐Regulated Expression; a newly developed technique which permits the trapping of acutely activated neuronal ensembles) and operant self‐administration (OSA), we tagged striatal neurons activated during alcohol‐taking behaviors. We used FLiCRE to express an inhibitory halorhodopsin in alcohol‐taking neurons, permitting loss‐of‐function manipulations.ResultsWe found that the inhibition of OSA‐tagged alcohol‐taking neurons decreased both alcohol‐seeking and ‐taking behaviors in future OSA trials. In addition, optogenetic inhibition of these OSA‐tagged alcohol‐taking neurons during extinction training facilitated the extinction of alcohol‐seeking behaviors. Furthermore, inhibition of these OSA‐tagged alcohol‐taking neurons suppressed the reinstatement of alcohol‐seeking behaviors, but, interestingly, it did not significantly suppress alcohol‐taking behaviors during reinstatement.ConclusionsOur findings suggest that alcohol‐taking neurons are crucial for future alcohol‐seeking behaviors during extinction and reinstatement. These results may help in the development of new therapeutic approaches to enhance extinction and suppress relapse in individuals with AUD.

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Experimental Models of Alcohol Use Disorder and Their Application for Pathophysiological Investigations

Cited by 3 publications

References 28 publications

JNK Signaling Positively Regulates Acute Ethanol Tolerance in C. elegans

JNK Signaling Positively Regulates Acute Ethanol Tolerance in C. elegans

Traumatic Brain Injury Exacerbates Alcohol Consumption and Neuroinflammation with Decline in Cognition and Cholinergic Activity

Optogenetic inhibition of light‐captured alcohol‐taking striatal engrams facilitates extinction and suppresses reinstatement

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