Midbrain circuit regulation of individual alcohol drinking behaviors in mice

Juarez, Barbara; Morel, Carole; Ku, Stacy M.; Liu, Yutong; Zhang, Hongxing; Montgomery, Sarah; Gregoire, H; Ribeiro, Efrain; Crumiller, Marshall; Roman-Ortiz, Ciorana; Walsh, Jessica J.; Jackson, Kelcy; Croote, Denise E.; Zhu, Yingbo; Zhang, Song; Vendruscolo, Leandro F.; Edwards, Scott; Roberts, Amanda J.; Hodes, Georgia E.; Lu, Yongke; Calipari, Erin S.; Chaudhury, Dipesh; Friedman, Allyson K.; Han, Ming–Hu

doi:10.1038/s41467-017-02365-8

Cited by 68 publications

(62 citation statements)

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“…Bursts were defined as the occurrence of two spikes at interspike interval <80 milliseconds and terminated when the interspike interval exceeded 160 milliseconds. 19 …”

Section: Methodsmentioning

confidence: 99%

Gabapentin regulates dopaminergic neuron firing and theta oscillation in the ventral tegmental area to reverse depression-like behavior in chronic neuropathic pain state

Wen

Wang

et al. 2018

JPR

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PurposeVentral tegmental area (VTA) dopamine system plays an important role in depression and is also involved in pain experience. In this study, we investigated the VTA dopaminergic (DA) neuron firing and local field potential (LFP) in pain-related depression, and we try to explore the underlying relationship between pain and depression.Materials and methodsWe used neuropathic pain model [spare nerve injury (SNI)] to induce pain-related depression. The Dixon up–down method was used to test mechanical hypersensitivity. Behavioral changes like open field test, sucrose preference test, and forced swim test were used to test depression-like behaviors. Gabapentin (GBP) was used to explore the chronic analgesic treatment that could reverse pain-related depression. To investigate the in vivo variations of VTA DA neuron firing and LFP, multichannel acquisition processor system was used.ResultsWe used SNI to induce depression-like behaviors. Repeated GBP treatment reversed these behaviors after 14 days of injection. An in vivo electrophysiological analysis of the firing characteristics of VTA DA neurons and LFP revealed that SNI increased the firing rate of DA neurons, but not the burst firing activity. Surprisingly, chronic GBP reversed the firing rate of DA neurons and reduced the burst firing activity. Moreover, SNI increased the LFP power in delta and theta oscillation and decreased it in beta oscillation. Repeated administration of GBP significantly suppressed theta oscillation. Above all, chronic GBP altered these characteristics to reverse depression-like behaviors.ConclusionThe present study confirmed that the tonic firing activity of VTA DA neurons, but not the burst firing activity, was the key factor in peripheral neuropathy–induced depression. Chronic GBP regulated the firing pattern of DA neurons and decreased theta oscillation in VTA to treat pain-related depression. This variation tendency of electrophysiological characteristics of VTA DA neurons and theta oscillation in VTA might represent an attempt to cope with pain-related negative mood disorder.

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“…Bursts were defined as the occurrence of two spikes at interspike interval <80 milliseconds and terminated when the interspike interval exceeded 160 milliseconds. 19 …”

Section: Methodsmentioning

confidence: 99%

Gabapentin regulates dopaminergic neuron firing and theta oscillation in the ventral tegmental area to reverse depression-like behavior in chronic neuropathic pain state

Wen

Wang

et al. 2018

JPR

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“…Our initial hypothesis focused on the reciprocal connections among regions of the extended amygdala and the VTA given that optogenetic and chemogenetic studies showed activation or inhibition of some of these neural pathways altered ethanol consumption [ 19 , 36 , 37 ]. We found that accumbal MSNs projecting to the VTA showed differential synaptic plasticity in HDID-1 and control mice after dependence and withdrawal from ethanol.…”

Section: Discussionmentioning

confidence: 99%

Dissecting Brain Networks Underlying Alcohol Binge Drinking Using a Systems Genomics Approach

et al. 2018

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Alcohol use disorder (AUD) is a complex psychiatric disorder with strong genetic and environmental risk factors. We studied the molecular perturbations underlying risky drinking behavior by measuring transcriptome changes across the neurocircuitry of addiction in a genetic mouse model of binge drinking. Sixteen generations of selective breeding for high blood alcohol levels after a binge drinking session produced global changes in brain gene expression in alcohol-naïve High Drinking in the Dark (HDID-1) mice. Using gene expression profiles to generate circuit-level hypotheses, we developed a systems approach that integrated regulation of gene coexpression networks across multiple brain regions, neuron-specific transcriptional signatures, and knowledgebase analytics. Whole-cell, voltage-clamp recordings from nucleus accumbens shell neurons projecting to the ventral tegmental area showed differential ethanol-induced plasticity in HDID-1 and control mice and provided support for one of the hypotheses. There were similarities in gene networks between HDID-1 mouse brains and postmortem brains of human alcoholics, suggesting that some gene expression patterns associated with high alcohol consumption are conserved across species. This study demonstrated the value of gene networks for data integration across biological modalities and species to study mechanisms of disease.

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“…Circuit‐probing techniques highlight the different contribution of VTA DA projections in the reinforcing properties of ethanol (Fig. ; Juarez et al., ). Interestingly, medial VTA DA neurons seem more responsive to ethanol (Fig.…”

Section: Reinforcing Properties Of Ethanol and Subsequent Neural Altementioning

confidence: 99%

“…Longer periods of alcohol exposure may induce homeostatic neuroadaptations not seen at short time intervals, but also the VTA DA neuron subpopulations investigated. Using a 10% ethanol 2BC paradigm of unlimited alcohol access, one group found that VTA‐NAc DA neurons had significantly increased I h current in low alcohol drinking mice and a significantly decreased I h current in high alcohol drinking mice when compared to controls (Juarez et al., ). In contrast, in vitro recordings made from VTA DA neurons 1–6 days after cessation of chronic ethanol consumption in mice (liquid diet, ~23 days) revealed decreases in baseline firing (Bailey et al., ).…”

Section: Reinforcing Properties Of Ethanol and Subsequent Neural Altementioning

confidence: 99%

“…A large majority of drugs, including nicotine and alcohol, activate this mesolimbic system and increase DA concentration in the NAc (Di Chiara & Imperato, , ; Imperato et al., ), a region known for encoding drug salience. In line with DA's role in natural reinforcement, learning and motivational processes, electrical and optogenetic stimulation (Tye & Deisseroth, ) of VTA DA neurons mimics and/or promotes drug intake behaviors (Juarez et al., ).…”

Section: Introductionmentioning

confidence: 99%

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Nicotine and alcohol: the role of midbrain dopaminergic neurons in drug reinforcement

Morel

Montgomery

Han

2018

Eur J of Neuroscience

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Nicotine and alcohol addiction are leading causes of preventable death worldwide and continue to constitute a huge socio‐economic burden. Both nicotine and alcohol perturb the brain's mesocorticolimbic system. Dopamine (DA) neurons projecting from the ventral tegmental area (VTA) to multiple downstream structures, including the nucleus accumbens, prefrontal cortex, and amygdala, are highly involved in the maintenance of healthy brain function. VTA DA neurons play a crucial role in associative learning and reinforcement. Nicotine and alcohol usurp these functions, promoting reinforcement of drug taking behaviors. In this review, we will first describe how nicotine and alcohol individually affect VTA DA neurons by examining how drug exposure alters the heterogeneous VTA microcircuit and network‐wide projections. We will also examine how coadministration or previous exposure to nicotine or alcohol may augment the reinforcing effects of the other. Additionally, this review briefly summarizes the role of VTA DA neurons in nicotine, alcohol, and their synergistic effects in reinforcement and also addresses the remaining questions related to the circuit‐function specificity of the dopaminergic system in mediating nicotine/alcohol reinforcement and comorbidity.

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Midbrain circuit regulation of individual alcohol drinking behaviors in mice

Cited by 68 publications

References 50 publications

Gabapentin regulates dopaminergic neuron firing and theta oscillation in the ventral tegmental area to reverse depression-like behavior in chronic neuropathic pain state

Gabapentin regulates dopaminergic neuron firing and theta oscillation in the ventral tegmental area to reverse depression-like behavior in chronic neuropathic pain state

Dissecting Brain Networks Underlying Alcohol Binge Drinking Using a Systems Genomics Approach

Nicotine and alcohol: the role of midbrain dopaminergic neurons in drug reinforcement

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