Publications by authors named "Matthew G Solomon"

6 Publications

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An Adolescent Porcine Model of Voluntary Alcohol Consumption Exhibits Binge Drinking and Motor Deficits in a Two Bottle Choice Test.

Alcohol Alcohol 2021 Apr;56(3):266-274

Regenerative Bioscience Center, University of Georgia, 425 River Road, Athens, GA, 30602, USA.

Aims: Alcohol is the most commonly abused substance leading to significant economic and medical burdens. Pigs are an attractive model for studying alcohol abuse disorder due to the comparable alcohol metabolism and consumption behavior, which are in stark contrast to rodent models. This study investigates the usage of a porcine model for voluntary binge drinking (BD) and a detailed analysis of gait changes due to motor function deficits during alcohol intoxication.

Methods: Adolescent pigs were trained to drink increasing concentration (0-8%) of alcohol mixed in a 0.2% saccharin solution for 1 h in a two bottle choice test for 2 weeks. The training period was followed by a 3-week alcohol testing period, where animals were given free access to 8% alcohol in 0.2% saccharin solution and 0.2% saccharin water solution. Blood alcohol levels were tested and gait analysis was performed pre-alcohol consumption, last day of training, and Day 5 of each testing period.

Results: Pigs voluntarily consumed alcohol to intoxication at all timepoints with blood alcohol concentration (BAL) ≥80 mg/dl. Spatiotemporal gait parameters including velocity, cadence, cycle time, swing time, stance time, step time, and stride length were perturbed as a result of intoxication. The stratification of the gait data based on BAL revealed that the gait parameters were affected in a dose-dependent manner.

Conclusion: This novel adolescent BD porcine model with inherent anatomical and physiological similarities to humans display similar consumption and intoxication behavior that is likely to yield results that are translatable to human patients.
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http://dx.doi.org/10.1093/alcalc/agaa105DOI Listing
April 2021

Intermittent Ethanol Access Increases Sensitivity to Social Defeat Stress.

Alcohol Clin Exp Res 2020 03 3;44(3):600-610. Epub 2020 Feb 3.

From the, Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, Georgia.

Background: Comorbidity between alcoholism and depression is extremely common. Recent evidence supports a relationship between alcohol exposure and stress sensitivity, an underlying factor in the development of depression. Our laboratory has recently shown that chronic alcohol gavage increases sensitivity to social defeat stress (SDS). However, the effects of voluntary alcohol consumption, resulting from protocols such as intermittent ethanol access (IEA), on defeat stress sensitivity have yet to be elucidated.

Methods: We first assessed the effects of 4 weeks of IEA to 20% alcohol on sensitivity to subthreshold SDS exposure. Next, to examine neuroinflammatory mechanisms, we analyzed gene expression of inhibitor of NFkB (IkB) following IEA or chronic alcohol exposure (10 days of 3.0 g/kg alcohol via intragastric gavage). Then, we quantified NFkB activation via β-galactosidase immunohistochemistry following IEA or chronic alcohol gavage in NFkB-LacZ mice.

Results: IEA-exposed mice displayed an increase in sensitivity to subthreshold SDS compared to water-drinking controls. We also found that IkB gene expression was decreased in the nucleus accumbens (NAC) and amygdala (AMY) following IEA but was not altered following chronic alcohol gavage. Finally, we observed increased NFkB activity in the central amygdala (CEA), basolateral amygdala (BLA), and medial amygdala (MEA) after IEA, and increased NFkB activity solely in the CEA following chronic alcohol gavage.

Conclusions: These findings further corroborate that prior alcohol exposure, in this case intermittent voluntary consumption, can impact development of depressive-like behavior by altering stress sensitivity. Furthermore, our results suggest the CEA as a potential mediator of alcohol's effects on stress sensitivity, as NFkB was activated in this region following both IEA and chronic alcohol gavage. Thus, this study provides novel insight on alterations in the NFkB pathway and identifies specific regions to target in future experiments assessing the functional role of NFkB in these processes.
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http://dx.doi.org/10.1111/acer.14278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069801PMC
March 2020

Brain Regional and Temporal Changes in BDNF mRNA and microRNA-206 Expression in Mice Exposed to Repeated Cycles of Chronic Intermittent Ethanol and Forced Swim Stress.

Neuroscience 2019 05 18;406:617-625. Epub 2019 Feb 18.

Charleston Alcohol Research Center, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC 29425, USA; Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29425, USA; RHJ Department of Veterans Affairs Medical Center, Charleston, SC 20401, USA. Electronic address:

Brain-derived neurotrophic factor (BDNF) expression and signaling activity in brain are influenced by chronic ethanol and stress. We previously demonstrated reduced Bdnf mRNA levels in the medial prefrontal cortex (mPFC) following chronic ethanol treatment and forced swim stress (FSS) enhanced escalated drinking associated with chronic ethanol exposure. The present study examined the effects of chronic ethanol and FSS exposure, alone and in combination, on Bdnf mRNA expression in different brain regions, including mPFC, central amygdala (CeA), and hippocampus (HPC). Additionally, since microRNA-206 has been shown to negatively regulate BDNF expression, the effects of chronic ethanol and FSS on its expression in the target brain regions were examined. Mice received four weekly cycles of chronic intermittent ethanol (CIE) vapor or air exposure and then starting 72-h later, the mice received either a single or 5 daily 10-min FSS sessions (or left undisturbed). Brain tissue samples were collected 4-h following final FSS testing and Bdnf mRNA and miR-206 levels were determined by qPCR assay. Results indicated dynamic brain regional and time-dependent changes in Bdnf mRNA and miR-206 expression. In general, CIE and FSS exposure reduced Bdnf mRNA expression while miR-206 levels were increased in the mPFC, CeA, and HPC. Further, in many instances, these effects were more robust in mice that experienced both CIE and FSS treatments. These results have important implications for the potential link between BDNF signaling in the brain and ethanol consumption related to stress interactions with chronic ethanol experience.
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http://dx.doi.org/10.1016/j.neuroscience.2019.02.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511465PMC
May 2019

Increasing Brain-Derived Neurotrophic Factor (BDNF) in medial prefrontal cortex selectively reduces excessive drinking in ethanol dependent mice.

Neuropharmacology 2018 09 26;140:35-42. Epub 2018 Jul 26.

Charleston Alcohol Research Center, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, 29425, USA; Department of Neuroscience, Medical University of South Carolina, Charleston, SC, 29425, USA; RHJ Department of Veterans Affairs Medical Center, Charleston, SC, 20401, USA. Electronic address:

The neurotrophin Brain-Derived Neurotrophic Factor (BDNF) has been implicated in a number of neuropsychiatric disorders, including alcohol use disorder. Studies have shown that BDNF activity in cortical regions, such as the medial prefrontal cortex (mPFC) mediates various ethanol-related behaviors. We previously reported a significant down-regulation in Bdnf mRNA in mPFC following chronic ethanol exposure compared to control mice. The present study was conducted to extend these findings by examining whether chronic ethanol treatment reduces BDNF protein expression in mPFC and whether reversing this deficit via direct injection of BDNF or viral-mediated overexpression of BDNF in mPFC alters voluntary ethanol consumption in dependent and nondependent mice. Repeated cycles of chronic intermittent ethanol (CIE) exposure was employed to model ethanol dependence, which produces robust escalation of ethanol intake. Results indicated that CIE treatment significantly increased ethanol intake and this was accompanied by a significant decrease in BDNF protein in mPFC that lasted at least 72 h after CIE exposure. In a separate study, once dependence-related increased drinking was established, bilateral infusion of BDNF (0, 0.25, 0.50 μg) into mPFC significantly decreased ethanol intake in a dose-related manner in dependent mice but did not affect moderate drinking in nondependent mice. In a third study, viral-mediated overexpression of BDNF in mPFC prevented escalation of drinking in dependent mice but did not alter intake in nondependent mice. Collectively, these results provide evidence that adaptations in cortical (mPFC) BDNF activity resulting from chronic ethanol exposure play a role in mediating excessive ethanol drinking associated with dependence.
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http://dx.doi.org/10.1016/j.neuropharm.2018.07.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113096PMC
September 2018

Cerebrospinal fluid monocyte chemoattractant protein-1 in alcoholics: support for a neuroinflammatory model of chronic alcoholism.

Alcohol Clin Exp Res 2014 May 1;38(5):1301-6. Epub 2014 Apr 1.

National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland.

Background: Liver inflammation in alcoholism has been hypothesized to influence the development of a neuroinflammatory process in the brain characterized by neurodegeneration and altered cognitive function. Monocyte chemoattractant protein-1/chemokine (C-C motif) ligand 2 (MCP-1/CCL2) elevations have been noted in the alcoholic brain at autopsy and may have a role in this process.

Methods: We studied cerebrospinal fluid (CSF) levels of MCP-1 as well as interleukin-1β and tumor necrosis factor-α in 13 healthy volunteers and 28 alcoholics during weeks 1 and 4 following detoxification. Serum liver enzymes were obtained as markers of alcohol-related liver inflammation.

Results: Compared to healthy volunteers, MCP-1 levels were significantly higher in alcoholics both on day 4 and day 25 (p < 0.0001). Using multiple regression analysis, we found that MCP-1 concentrations were positively associated with the liver enzymes gamma glutamyltransferase (GGT; p = 0.03) and aspartate aminotransferase/glutamic oxaloacetic transaminase (AST/GOT; p = 0.004).

Conclusions: These preliminary findings are consistent with the hypothesis that neuroinflammation as indexed by CSF MCP-1 is associated with alcohol-induced liver inflammation, as defined by peripheral concentrations of GGT and AST/GOT.
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http://dx.doi.org/10.1111/acer.12367DOI Listing
May 2014

Tacr1 gene variation and neurokinin 1 receptor expression is associated with antagonist efficacy in genetically selected alcohol-preferring rats.

Biol Psychiatry 2013 Apr 16;73(8):774-81. Epub 2013 Feb 16.

Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institute of Health, Bethesda, MD 20892-1108, USA.

Background: Genetic deletion or antagonism of the neurokinin 1 receptor (NK1R) decreases alcohol intake, alcohol reward, and stress-induced alcohol relapse in rodents, while TACR1 variation is associated with alcoholism in humans.

Methods: We used L822429, a specific antagonist with high affinity for the rat NK1R, and examined whether sensitivity to NK1R blockade is altered in alcohol-preferring (P) rats. Operant alcohol self-administration and progressive ratio responding were analyzed in P-rats and their founder Wistar line. We also analyzed Tacr1 expression and binding and sequenced the Tacr1 promoter from both lines.

Results: Systemic L822429 decreased alcohol self-administration in P-rats but did not affect the lower rates of alcohol self-administration in Wistar rats. Tacr1 expression was elevated in the prefrontal cortex and the amygdala of P-rats. In central amygdala, elevated Tacr1 expression was accompanied by elevated NK1R binding. Central amygdala (but not prefrontal cortex) infusion of L822429 replicated the systemic antagonist effects on alcohol self-administration in P-rats. All P-rats, but only 18% of their founder Wistar population, were CC homozygous for a-1372G/C single nucleotide polymorphism. In silico analysis indicated that the Tacr1-1372 genotype could modulate binding of the transcription factors GATA-2 and E2F-1. Electromobility shift and luciferase reporter assays suggested that the-1372C allele confers increased transcription factor binding and transcription.

Conclusions: Genetic variation at the Tacr1 locus may contribute to elevated rates of alcohol self-administration, while at the same time increasing sensitivity to NK1R antagonist treatment.
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http://dx.doi.org/10.1016/j.biopsych.2012.12.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773538PMC
April 2013