Animal models of binge drinking, current challenges to improve face validity

Jeanblanc, Jérôme; Rolland, Benjamin; Gierski, Fabien; Martinetti, Margaret P.; Naassïla, Mickaël

doi:10.1016/j.neubiorev.2018.05.002

Cited by 41 publications

(42 citation statements)

References 117 publications

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“…Binge drinking or consuming a large amount of alcohol in a short period of time is an increasingly significant public health issue. Animal studies found that binge-like drinking patterns, in which the fetus was exposed to high BACs over relatively short periods of time, were harmful as evidenced by acute apoptosis and long-term cognitive dysfunction 107 – 110 . One of the main gaps in knowledge for ethanol-induced brain injury is regarding dose-response relationships.…”

Section: Discussionmentioning

confidence: 99%

Modeling alcohol-induced neurotoxicity using human induced pluripotent stem cell-derived three-dimensional cerebral organoids

et al. 2020

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Maternal alcohol exposure during pregnancy can substantially impact the development of the fetus, causing a range of symptoms, known as fetal alcohol spectrum disorders (FASDs), such as cognitive dysfunction and psychiatric disorders, with the pathophysiology and mechanisms largely unknown. Recently developed human cerebral organoids from induced pluripotent stem cells are similar to fetal brains in the aspects of development and structure. These models allow more relevant in vitro systems to be developed for studying FASDs than animal models. Modeling binge drinking using human cerebral organoids, we sought to quantify the downstream toxic effects of alcohol (ethanol) on neural pathology phenotypes and signaling pathways within the organoids. The results revealed that alcohol exposure resulted in unhealthy organoids at cellular, subcellular, bioenergetic metabolism, and gene expression levels. Alcohol induced apoptosis on organoids. The apoptotic effects of alcohol on the organoids depended on the alcohol concentration and varied between cell types. Specifically, neurons were more vulnerable to alcohol-induced apoptosis than astrocytes. The alcohol-treated organoids exhibit ultrastructural changes such as disruption of mitochondria cristae, decreased intensity of mitochondrial matrix, and disorganized cytoskeleton. Alcohol exposure also resulted in mitochondrial dysfunction and metabolic stress in the organoids as evidenced by (1) decreased mitochondrial oxygen consumption rates being linked to basal respiration, ATP production, proton leak, maximal respiration and spare respiratory capacity, and (2) increase of non-mitochondrial respiration in alcohol-treated organoids compared with control groups. Furthermore, we found that alcohol treatment affected the expression of 199 genes out of 17,195 genes analyzed. Bioinformatic analyses showed the association of these dysregulated genes with 37 pathways related to clinically relevant pathologies such as psychiatric disorders, behavior, nervous system development and function, organismal injury and abnormalities, and cellular development. Notably, 187 of these genes are critically involved in neurodevelopment, and/or implicated in nervous system physiology and neurodegeneration. Furthermore, the identified genes are key regulators of multiple pathways linked in networks. This study extends for the first time animal models of binge drinking-related FASDs to a human model, allowing in-depth analyses of neurotoxicity at tissue, cellular, subcellular, metabolism, and gene levels. Hereby, we provide novel insights into alcohol-induced pathologic phenotypes, cell type-specific vulnerability, and affected signaling pathways and molecular networks, that can contribute to a better understanding of the developmental neurotoxic effects of binge drinking during pregnancy.

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Section: Discussionmentioning

confidence: 99%

Modeling alcohol-induced neurotoxicity using human induced pluripotent stem cell-derived three-dimensional cerebral organoids

et al. 2020

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“…Understanding the brain mechanisms by which vulnerable individuals develop unmanageable patterns of consumption of food or alcohol is key in order to improve treatments and prevent addiction. Over the last decade an increasing number of studies have used animal models that attempt to mimic binge intake (Thiele and Navarro, 2014;Jeanblanc et al, 2018;Treasure and Eid, 2019). Originally designed to study high voluntary EtOH consumption achieving behaviorally-intoxicating BECs, the DID model has been extensively used to investigate the neurobiology of binge-like EtOH intake (Rhodes et al, 2005;Thiele and Navarro, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…One model known as drinking-in-the-dark (DID) takes advantage of rodents' natural circadian rhythms in order to promote high levels of voluntary EtOH drinking (Rhodes et al, 2005). Using this methodology, EtOH-preferring mice consume enough EtOH to show behavioral and pharmacological signs of intoxication that are relevant to human behavior, illustrating the face validity of this procedure (Rhodes et al, 2005;Thiele and Navarro, 2014;Jeanblanc et al, 2018). Although DID has primarily been used to study the neurobiology of binge-like EtOH drinking, it can also produce elevated consumption of other drugs of abuse, including methamphetamine (Fultz et al, 2017) and opioids (Szumlinski et al, 2019) and other tastants like sugar (Kamdar et al, 2007;Cozzoli et al, 2012;Giardino and Ryabinin, 2013;Holgate et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Effects of naltrexone on alcohol, sucrose, and saccharin binge-like drinking in C57BL/6J mice: a study with a multiple bottle choice procedure

Morales

Rodríguez-Borillo

Font

et al. 2020

Behavioural Pharmacology

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Chronic alcohol (EtOH) binging has been associated with long-term neural adaptations that lead to the development of addiction. Many of the neurobiological features of EtOH abuse are shared with other forms of binging, like pathological feeding. The drinkingin-the-dark paradigm (DID) has been used extensively to study the neurobiology of EtOH binge-like drinking due to its ability to promote high intakes relevant to human behavior. DID can also generate high consumption of other tastants, but this procedure has not been fully adapted to study forms of binging behavior that are not alcohol-driven. In the present study we used a modified version of DID that uses multiple bottle availability to promote even higher levels of EtOH drinking in male C57BL/6J mice and allows a thorough investigation of tastant preferences. We assessed whether administration of systemic naltrexone (NTX) could reduce binging on EtOH, sucrose, and saccharin separately as well as in combination. Our multiple bottle DID procedure resulted in heightened levels of consumption compared to previously reported data using this task. We found that administration of the opioid receptor antagonist NTX reduced intakes of preferred, highly concentrated EtOH, sucrose, and saccharin. We also report that NTX was able to reduce overall intakes when animals were allowed to self-administer EtOH, sucrose, or saccharin in combination. Our modified DID procedure provides a novel approach to study binging behavior that extends beyond EtOH to other tastants (i.e., sucrose and artificial sweeteners), and has implications for the study of the neuropharmacology of binge drinking.

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“…Rats exposed to this procedure consume the most abundant amount of their daily total intake within the first hour of availability of the alcohol bottle, reaching intoxicating blood alcohol levels in a short period of time (about mg/dl after the first 30 min–1 h, Simms et al, 2008 ; Carnicella et al, 2009 ; Loi et al, 2014 ). This procedure models a voluntary binge-like drinking pattern (Crabbe et al, 2011 ; Sprow and Thiele, 2012 ; Sabino et al, 2013 ; Carnicella et al, 2014 ; Spear, 2018 ; Jeanblanc et al, 2019 ) and, as such, may represent a valuable tool to model drinking trajectories during pregnancy and lactation. Interestingly, when female rats are exposed to a long-term binge-like intermittent alcohol drinking (IAD) paradigm, they display a significant decrease in alcohol consumption during pregnancy and resume excessive alcohol consumption during the lactation period (Brancato et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Environmental Enrichment During Adolescence Mitigates Cognitive Deficits and Alcohol Vulnerability due to Continuous and Intermittent Perinatal Alcohol Exposure in Adult Rats

Brancato

Castelli

Lavanco

et al. 2020

Front. Behav. Neurosci.

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Perinatal alcohol exposure affects ontogenic neurodevelopment, causing physical and functional long-term abnormalities with limited treatment options. This study investigated long-term consequences of continuous and intermittent maternal alcohol drinking on behavioral readouts of cognitive function and alcohol vulnerability in the offspring. The effects of environmental enrichment (EE) during adolescence were also evaluated. Female rats underwent continuous alcohol drinking (CAD)-or intermittent alcohol drinking paradigm (IAD), along pregestation, gestation, and lactation periods-equivalent to the whole gestational period in humans. Male offspring were reared in standard conditions or EE until adulthood and were then assessed for declarative memory in the novel object recognition test; spatial learning, cognitive flexibility, and reference memory in the Morris water maze (MWM); alcohol consumption and relapse by a two-bottle choice paradigm. Our data show that perinatal CAD decreased locomotor activity, exploratory behavior, and declarative memory with respect to controls, whereas perinatal IAD displayed impaired declarative memory and spatial learning and memory. Moreover, both perinatal alcohol-exposed offspring showed higher vulnerability to alcohol consummatory behavior than controls, albeit perinatal IAD rats showed a greater alcohol consumption and relapse behavior with respect to perinatal-CAD progeny. EE ameliorated declarative memory in perinatal CAD, while it mitigated spatial learning and reference memory impairment in perinatal-IAD progeny. In addition, EE decreased vulnerability to alcohol in both control and perinatal alcohol-exposed rats. Maternal alcohol consumption produces drinking pattern-related

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Animal models of binge drinking, current challenges to improve face validity

Cited by 41 publications

References 117 publications

Modeling alcohol-induced neurotoxicity using human induced pluripotent stem cell-derived three-dimensional cerebral organoids

Modeling alcohol-induced neurotoxicity using human induced pluripotent stem cell-derived three-dimensional cerebral organoids

Effects of naltrexone on alcohol, sucrose, and saccharin binge-like drinking in C57BL/6J mice: a study with a multiple bottle choice procedure

Environmental Enrichment During Adolescence Mitigates Cognitive Deficits and Alcohol Vulnerability due to Continuous and Intermittent Perinatal Alcohol Exposure in Adult Rats

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