Repeated cycles of chronic intermittent ethanol exposure in mice increases voluntary ethanol drinking and ethanol concentrations in the nucleus accumbens

Griffin, William C.; López, Marcelo F.; Yanke, Amy B.; Middaugh, Lawrence D.; Becker, Howard C.

doi:10.1007/s00213-008-1324-3

Cited by 126 publications

(170 citation statements)

References 25 publications

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“…Mice were trained to drink ethanol in the home cage under a limited access, 2-bottle choice situation as previously described (Becker and Lopez, 2004;Griffin et al, 2009a;Griffin et al, 2009b;Lopez and Becker, 2005). A modified sucrose fading procedure was used, with 15% (v/v) ethanol as the final solution along with tap water as the alternative fluid.…”

Section: Limited Access Drinking Proceduresmentioning

confidence: 99%

“…CIE (or air) vapor exposure was delivered in Plexiglas inhalation chambers as previously described (Becker and Lopez, 2004;Griffin et al, 2009b). Chamber ethanol concentrations were monitored daily and air flow was adjusted to maintain ethanol concentrations within a range that yielded stable blood ethanol levels throughout exposure (175-225 mg/dl).…”

Section: Cie Exposure Proceduresmentioning

confidence: 99%

“…For microinjection studies, bilateral guide cannulae (Plastics One; Roanoke, VA) were positioned above the NAc (relative to Bregma: AP þ 1.7, ML ±0.75, and DV À 3.9). In both cases, guides were secured to the skull using a light-cured resin system and the guide obdurators remained in place until use (Griffin et al, 2009b). Mice were allowed a minimum of 10 days to recover from surgery before starting an experiment.…”

Section: Stereotaxic Surgerymentioning

confidence: 99%

“…As previously described (Griffin et al, 2009b;Griffin et al, 2007), microdialysis probes (CMA/7) were implanted the day before sample collection and aCSF was perfused through the probe during the overnight period at 0.2 ml/min (probes extended 1 mm beyond the guide cannulae). The next day, the flow was increased to 1 ml/min and allowed to equilibrate for 2 h before beginning the serial dialysate collection in 15 min intervals.…”

Section: Microdialysis Proceduresmentioning

confidence: 99%

“…We have developed a mouse model of ethanol dependence and relapse drinking that involves repeated cycles of chronic ethanol exposure and withdrawal periods and produces significant escalation of voluntary alcohol drinking in dependent compared with nondependent mice (Becker, 2008;Becker and Lopez, 2004;Griffin et al, 2009b;Lopez and Becker, 2005). Given that chronic ethanol induces significant alterations in glutamate activity in several brain regions, and adaptive changes in glutamate transmission have been postulated to have a significant role in the addiction process (Kalivas, 2009), our mouse model of dependence and relapse drinking would appear ideal for examining the relationship between dependence-related adaptations in glutamate activity and increased alcohol consumption.…”

Section: Introductionmentioning

confidence: 99%

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Increased Extracellular Glutamate In the Nucleus Accumbens Promotes Excessive Ethanol Drinking in Ethanol Dependent Mice

Griffin

Haun

Hazelbaker

et al. 2013

Neuropsychopharmacol

129

112

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Using a well-established model of ethanol dependence and relapse, this study examined adaptations in glutamatergic transmission in the nucleus accumbens (NAc) and their role in regulating voluntary ethanol drinking. Mice were first trained to drink ethanol in a free-choice, limited access (2 h/day) paradigm. One group (EtOH mice) received repeated weekly cycles of chronic intermittent ethanol (CIE) exposure with intervening weeks of test drinking sessions, whereas the remaining mice (CTL mice) were similarly treated but did not receive CIE treatment. Over repeated cycles of CIE exposure, EtOH mice exhibited significant escalation in drinking (up to B3.5 g/kg), whereas drinking remained relatively stable at baseline levels (2-2.5 g/kg) in CTL mice. Using in vivo microdialysis procedures, extracellular glutamate (GLU EX ) levels in the NAc were increased approximately twofold in EtOH mice compared with CTL mice, and this difference was observed 7 days after final CIE exposure, indicating that this hyperglutamatergic state persisted beyond acute withdrawal. This finding prompted additional studies examining the effects of pharmacologically manipulating GLU EX in the NAc on ethanol drinking in the CIE model. The non-selective glutamate reuptake antagonist, threo-b-benzyloxyaspartate (TBOA), was bilaterally microinjected into the NAc and found to dose-dependently increase drinking in nondependent (CTL) mice to levels attained by dependent (EtOH) mice. TBOA also further increased drinking in EtOH mice. In contrast, reducing glutamatergic transmission in the NAc via bilateral injections of the metabotropic glutamate receptor-2/3 agonist LY379268 reduced drinking in dependent (EtOH) mice to nondependent (CTL) levels, whereas having a more modest effect in decreasing ethanol consumption in CTL mice. Taken together, these data support an important role of glutamatergic transmission in the NAc in regulating ethanol drinking. Additionally, these results indicate that ethanol dependence produces adaptations that favor elevated glutamate activity in the NAc which, in turn, promote excessive levels of ethanol consumption associated with dependence.

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Section: Limited Access Drinking Proceduresmentioning

confidence: 99%

Section: Cie Exposure Proceduresmentioning

confidence: 99%

Section: Stereotaxic Surgerymentioning

confidence: 99%

Section: Microdialysis Proceduresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Increased Extracellular Glutamate In the Nucleus Accumbens Promotes Excessive Ethanol Drinking in Ethanol Dependent Mice

Griffin

Haun

Hazelbaker

et al. 2013

Neuropsychopharmacol

129

112

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Adolescent intermittent ethanol exposure induces sex‐dependent divergent changes in ethanol drinking and motor activity in adulthood in C57BL/6J mice

Maldonado‐Devincci

Makdisi

Hill

et al. 2021

J of Neuroscience Research

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With alcohol readily accessible to adolescents, its consumption leads to many adverse effects, including impaired learning, attention, and behavior. Adolescents report higher rates of binge drinking compared to adults. They are also more prone to substance use disorder in adulthood due to physiological changes during the adolescent developmental period. We used C57BL/6J male and female mice to investigate the long‐lasting impact of binge ethanol exposure during adolescence on voluntary ethanol intake and open field behavior during later adolescence (Experiment 1) and during emerging adulthood (Experiment 2). The present set of experiments were divided into four stages: (1) adolescent intermittent vapor inhalation exposure, (2) abstinence, (3) voluntary ethanol intake, and (4) open field behavioral testing. During adolescence, male and female mice were exposed to air or ethanol using intermittent vapor inhalation from postnatal day (PND) 28–42. Following this, mice underwent short‐term abstinence from PND 43–49 (Experiment 1) or protracted abstinence from PND 43–69 (Experiment 2). Beginning on PND 50–76 or PND 70–97, mice were assessed for intermittent voluntary ethanol consumption using a two‐bottle choice drinking procedure over 28 days. Male adolescent ethanol‐exposed mice showed increased ethanol consumption following short‐term abstinence and following protracted abstinence. In contrast, female mice showed no changes in ethanol consumption following short‐term abstinence and decreased ethanol consumption following protracted abstinence. There were modest changes in open field behavior following voluntary ethanol consumption in both experiments. These data demonstrate a sexually divergent shift in ethanol consumption following binge ethanol exposure during adolescence and differences in open field behavior. These results highlight sex‐dependent vulnerability to developing substance use disorders in adulthood.

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Cross-Species Alterations in Synaptic Dopamine Regulation After Chronic Alcohol Exposure

Siciliano

Karkhanis

Holleran

et al. 2018

Handbook of Experimental Pharmacology

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Alcohol use disorders are a leading public health concern, engendering enormous costs in terms of both economic loss and human suffering. These disorders are characterized by compulsive and excessive alcohol use, as well as negative affect and alcohol craving during abstinence. Extensive research has implicated the dopamine system in both the acute pharmacological effects of alcohol and the symptomology of alcohol use disorders that develop after extended alcohol use. Preclinical research has shed light on many mechanisms by which chronic alcohol exposure dysregulates the dopamine system. However, many of the findings are inconsistent across experimental parameters such as alcohol exposure length, route of administration, and model organism. We propose that the dopaminergic alterations driving the core symptomology of alcohol use disorders are likely to be relatively stable across experimental settings. Recent work has been aimed at using multiple model organisms (mouse, rat, monkey) across various alcohol exposure procedures to search for commonalities. Here, we review recent advances in our understanding of the effects of chronic alcohol use on the dopamine system by highlighting findings that are consistent across experimental setting and species.

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Repeated cycles of chronic intermittent ethanol exposure in mice increases voluntary ethanol drinking and ethanol concentrations in the nucleus accumbens

Cited by 126 publications

References 25 publications

Increased Extracellular Glutamate In the Nucleus Accumbens Promotes Excessive Ethanol Drinking in Ethanol Dependent Mice

Increased Extracellular Glutamate In the Nucleus Accumbens Promotes Excessive Ethanol Drinking in Ethanol Dependent Mice

Adolescent intermittent ethanol exposure induces sex‐dependent divergent changes in ethanol drinking and motor activity in adulthood in C57BL/6J mice

Cross-Species Alterations in Synaptic Dopamine Regulation After Chronic Alcohol Exposure

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