Stress Increases Ethanol Self-Administration via a Shift toward Excitatory GABA Signaling in the Ventral Tegmental Area

Ostroumov, Alexey; Thomas, Alyse M.; Kimmey, Blake A.; Karsch, Jordan S.; Doyon, William M.; Dani, John A.

doi:10.1016/j.neuron.2016.09.029

Cited by 85 publications

(167 citation statements)

References 40 publications

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“…In Cozzoli et al [36] restraint stress decreased ethanol consumption during 2h-access in DID for at least 2 days in mice. On the other hand, 15 hours after immobilization stress (1 h) rats self-administered significantly more ethanol at least over 12 days [50]. In the present study, over the next 22 h, the control group exhibited a recovery in the amount of alcohol consumed comparable to the amount they had consumed in the previous week, reaching similar levels of intake as those that were reached during the week without restraint stress.…”

Section: Discussionsupporting

confidence: 59%

Environmental Enrichment Blunts Ethanol Consumption after Restraint Stress in C57BL/6 Mice

2017

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Elevated alcohol intake after abstinence is a key feature of the addiction process. Some studies have shown that environmental enrichment (EE) affects ethanol intake and other reinforcing effects. However, different EE protocols may vary in their ability to influence alcohol consumption and stress-induced intake. The present study evaluated whether short (3 h) or continuous (24 h) EE protocols affect ethanol consumption after periods of withdrawal. Mice were challenged with stressful stimuli (24 h isolation and restraint stress) to evaluate the effects of stress on drinking. Male C57BL/6 mice were subjected to a two-bottle choice drinking-in-the-dark paradigm for 15 days (20% ethanol and water, 2 h/day, acquisition phase). Control mice were housed under standard conditions (SC). In the first experiment, one group of mice was housed under EE conditions 24 h/day (EE24h). In the second experiment, the exposure to EE was reduced to 3 h/day (EE3h). After the acquisition phase, the animals were deprived of ethanol for 6 days, followed by 2 h ethanol access once a week. Animals were tested in the elevated plus maze (EPM) during ethanol withdrawal. During the last 2 weeks, the mice were exposed to 24 h ethanol access. A 1-h restraint stress test was performed immediately before the last ethanol exposure. EE24h but not EE3h increased anxiety-like behavior during withdrawal compared to controls. Neither EE24h nor EE3h affected ethanol consumption during the 2 h weekly exposure periods. However, EE24h and EE3h mice that were exposed to acute restraint stress consumed less ethanol than controls during a 24 h ethanol access. These results showed that EE reduces alcohol intake after an acute restraint stress.

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Section: Discussionsupporting

confidence: 59%

Environmental Enrichment Blunts Ethanol Consumption after Restraint Stress in C57BL/6 Mice

2017

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“…For example, acute restraint stress in rats increases ethanol self-administration and this correlates with an abolished ethanol-induced increase in DA neurons firing. 38 Here we clearly show that chronic nicotine administration or chronic social stress blunts the ability of nicotine to activate VTA DA neurons. This could reflect a remodeling of inhibitory and excitatory local connectivity in the VTA.…”

Section: Discussionmentioning

confidence: 57%

Nicotinic receptors mediate stress-nicotine detrimental interplay via dopamine cells’ activity

et al. 2017

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Epidemiological studies report strong association between mood disorders and tobacco addiction. This high comorbidity requires adequate treatment but the underlying mechanisms are unknown. We demonstrate that nicotine exposure, independent of drug withdrawal effects, increases stress sensitivity, a major risk factor in mood disorders. Nicotine and stress concur to induce long-lasting cellular adaptations within the dopamine (DA) system. This interplay is underpinned by marked remodeling of nicotinic systems, causing increased ventral tegmental area (VTA) DA neurons' activity and stress-related behaviors, such as social aversion. Blocking β2 or α7 nicotinic acetylcholine receptors (nAChRs) prevents, respectively, the development and the expression of social stress-induced neuroadaptations; conversely, facilitating α7 nAChRs activation specifically in the VTA promotes stress-induced cellular and behavioral maladaptations. Our work unravels a complex nicotine-stress bidirectional interplay and identifies α7 nAChRs as a promising therapeutic target for stress-related psychiatric disorders.

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“…Stressinduced EtOH consumption is regulated by glucocorticoids (Ostroumov et al 2016), suggesting that the elevated glucocorticoid tone in β-E À/À female mice may contribute to their increased EtOH consumption.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in binge‐like EtOH drinking, corticotropin‐releasing hormone and corticosterone: effects of β‐endorphin

et al. 2018

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Binge drinking is an increasingly common pattern of risky use associated with numerous health problems, including alcohol use disorders. Because low basal plasma levels of β-endorphin (β-E) and an increased β-E response to alcohol are evident in genetically at-risk human populations, this peptide is thought to contribute to the susceptibility for disordered drinking. Animal models suggest that the effect of β-E on consumption may be sex-dependent. Here, we studied binge-like EtOH consumption in transgenic mice possessing varying levels of β-E: wild-type controls with 100% of the peptide (β-E +/+), heterozygous mice constitutively modified to possess 50% of wild-type levels (β-E +/À) and mice entirely lacking the capacity to synthesize β-E (À/À). These three genotypes and both sexes were evaluated in a 4-day, two-bottle choice, drinking in the dark paradigm with limited access to 20% EtOH. β-E deficiency determined sexually divergent patterns of drinking in that β-E À/À female mice drank more than their wild-type counterparts, an effect not observed in male mice. β-E À/À female mice also displayed elevated basal anxiety, plasma corticosterone and corticotropin-releasing hormone mRNA in the extended amygdala, and all of these were normalized by EtOH selfadministration. These data suggest that a heightened risk for excessive EtOH consumption in female mice is related to the drug's ability to ameliorate an overactive anxiety/stress-like state. Taken together, our study highlights a critical impact of sex on neuropeptide regulation of EtOH consumption.

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Stress Increases Ethanol Self-Administration via a Shift toward Excitatory GABA Signaling in the Ventral Tegmental Area

Cited by 85 publications

References 40 publications

Environmental Enrichment Blunts Ethanol Consumption after Restraint Stress in C57BL/6 Mice

Environmental Enrichment Blunts Ethanol Consumption after Restraint Stress in C57BL/6 Mice

Nicotinic receptors mediate stress-nicotine detrimental interplay via dopamine cells’ activity

Sex differences in binge‐like EtOH drinking, corticotropin‐releasing hormone and corticosterone: effects of β‐endorphin

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