Dopaminergic hypofunction in alcohol dependence: From rodents to humans
Dopamine is an important mediator of the reinforcing effects of drugs of abuse, and alterations in dopamine function might be involved in drug addiction. In particular, basic studies have documented a reduction in the electrophysiological activity of dopamine neurons in alcohol, opiate and cannabinoid dependent rats. Further, dopamine release in the Nucleus Accumbens (Nacc) is decreased in, virtually all, drug-dependent rodents. In parallel, these studies are supported by increments in Intracranial Self Stimulation (ICSS) thresholds during withdrawal from alcohol, nicotine, opiates and other drugs of abuse thereby suggesti...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Marco Diana Tags: Roundtable Source Type: research
A human laboratory study of mifepristone as a novel treatment for alcohol use disorder
Advances in the neurobiology of alcohol use disorder (AUD) have highlighted an association between dysregulation of central stress systems and risk of drinking relapse during protracted abstinence. Potential treatment targets include the hypothalamic-pituitary-adrenal (HPA) axis and impairment in glucocorticoid receptor (GR) feedback and activity. We hypothesized that treatment with the mixed GR/progesterone receptor anatagonist, mifepristone, would reduce alcohol craving and drinking in non treatment-seeking outpatient alcoholics relative to placebo. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Barbara J. Mason Source Type: research
Digital technology for the discovery and managements of novel treatments for alcoholism and psychiatric disorders: A quantum leap?
The disruptive contribution of digital technology in medicine has been highlighed initially by few medical “futurologists” and more recently by the consistent intention of the most advanced pharma industry to partner with cutting-edge Information Technology industries, with a somewhat slower engagement of academic centres. In this presentation the scientific literature about the validation of digital technology tools to assess the condition of patients affected by alcoholism and psychiatric disorders will be reviewed. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Emilio Merlo Pich Source Type: research
Effect of the mGluR5 modulator GET 73 on alcohol pharmaco-kinetics and pharmacodynamics and alcohol craving in a human laboratory model
GET 73 is a novel, small molecule compound that reduces alcohol consumption and appears to have some anxiolytic and anti-stress activity in animal models. Although the mechanism of action of GET 73 is not entirely understood, the drug appears to act as a negative allosteric modulator (NAM) at the mGluR5 receptor. mGluR5 NAMs could reduce the hyperglutamatergic / high stress / allostatic state associated with alcohol dependence. To better understand the mechanism of action of GET 73 in reducing alcohol consumption, to examine its potential interactions with alcohol pharmacokinetics and pharmacodynamics, and to determine its...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Robert Swift, Julia Wood, Jonathan Franco, Roberto Cacciaglia Source Type: research
CeA projections to PAG mediate stress- and alcohol dependence-induced hyperalgesia in rats
Hyperalgesia is an exaggerated response to noxious stimuli resulting from physical insult (e.g., nerve injury) or psychological phenomena. The central amygdala (CeA) receives information from multiple pathways carrying nociceptive information in the central nervous system and projects to regions which gate descending pathways that modulate nociceptive afferent activity, including the periaqueductal gray (PAG). We have recently demonstrated a role for corticotropin-releasing factor (CRF) signaling in CeA in mediating hyperalgesia after stress. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Elizabeth M. Avegno, Christy A. Itoga, Annie M. Whitaker, Thomas Lobell, Nicholas W. Gilpin Tags: Posters Source Type: research
Chronic ethanol-induced immune responses in the mouse central amygdala: Focus on glia and IL-1 system
In this study, we focused on the chronic ethanol-induced immune response mediated by the innate immune system in the central nucleus of the amygdala (CeA). We used a 2BC-CIE (two-bottle choice - chronic ethanol intermittent vapor exposure) paradigm to induce ethanol dependence in C57BL/6J mice. Using immunohistochemistry, we examined the expression of microglial markers (Iba-1 and CD11b) and morphological changes of microglia in the CeA of ethanol naive, non-dependent and dependent mice. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Michal Bajo, Michael Q. Steinman, Florence P. Varodayan, Sophia Khom, Reesha R. Patel, David M. Hedges, Melissa A. Herman, Sarah E. Montgomery, Tali Nadav, Noah Steiner, Chitra D. Mandyam, Amanda J. Roberts, Marisa Roberto Source Type: research
Circulating gonadal hormones influence alcohol-motivated behavior in male and female rats
Ample research shows that female rodents demonstrate enhanced alcohol-motivated behavior compared to males. However, the mechanism underlying these sex differences is unclear. Evidence suggests that estradiol promotes, whereas testosterone reduces alcohol drinking, though few, if any, studies have determined gonadal hormone-mediated changes in the reinstatement of ethanol seeking. To explore this, gonadally intact and gonadectomized (GDX) female and male rats were given estradiol (E2) or testosterone (T) replacement, respectively, during operant ethanol self-administration. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: M.L. Bertholomey, M.M. Torregrossa Source Type: research
Low dose systemic ethanol increases dopamine receptor desensiti-zation and GRK2 mRNA in the ventral tegmental area of C57Bl/6J mice
The ventral tegmental area (VTA) is important for rewarding and reinforcing effects of natural substances and drugs, including ethanol. Alteration in the neurophysiology of dopaminergic (DA) VTA neurons by low dose alcohol may lead to enhanced responses to subsequent alcohol exposures, and promote loss of control of alcohol intake. The dopamine D2 autoreceptor is a major physiological modulator of DA VTA neuronal activity. In the presence of sustained, moderate dopamine concentrations, D2 receptors undergo desensitization, which is an important regulatory feedback control mechanism. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Mark S. Brodie, Chang You, Bertha J. Vandegrift Source Type: research
Effects of environmental enrichment on anxiety-like behavior and ethanol intake in C57BL/6 mice
Keywords: ethanol, stress, two-bottle choice, environmental enrichment. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Gabriel de Ara újo Costa, Priscila Marianno, Rosana Camarini Source Type: research
Forced abstinence from ethanol intake dysregulates behavioral affect and endocannabinoid control of a BNST circuit
Alcohol use disorders (AUDs) are strongly comorbid with depression, and alcohol withdrawal is considered a potent stressor associated with affective disturbances. The interaction between AUDs and depression represents an understudied area of research that could yield therapeutics aimed at treating alcohol abstinence-induced affective behaviors. To this end, we used a two-bottle choice mouse model of chronic ethanol drinking followed by forced abstinence (CDFA). CDFA produces consistent ethanol preference and a depressive-like phenotype during prolonged abstinence in female C57BL/6J mice. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Samuel W. Centanni, Katherine M. Holleran, Sachin Patel, Danny G. Winder Source Type: research
Neural responses to alcohol and negative cues in heavy drinkers and relationships with AUD severity
Altered physiological response to alcohol and stress cues among individuals with alcohol use disorders is well established. While neural responses to both alcohol and stress cues are able to predict relapse, less is known about the relationship with AUD severity. The purpose of the current study was to examine responses to alcohol and stress cues and how these responses related to AUD severity. Non-treatment seeking, heavy drinking individuals were recruited for this study. After completing a baseline assessment of drinking, cognitive and emotional functioning, and psychiatric symptomatology, participants completed a basel...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Eric D. Claus, Katie Witkiewitz Source Type: research
Using High Drinking in the Dark (HDID) mice as an animal model to identify drugs to reduce alcohol binge-like drinking
One characteristic of nearly all abusive alcohol drinking is the tendency to drink in binges, defined by the NIAAA as a pattern leading to blood alcohol levels (BALs)> 0.08% (i.e., exceeding the legal limit for driving) during a period of approximately 2 hr. We bred two mouse lines that drink to intoxication and reach high BALs (> 0.14%) after 2-4 hr access to alcohol early during their circadian dark period. Here we show that HDID mice fail to reduce drinking or BALs after drugs that reduce intake in other drinking models (e.g., naltrexone and several experimental drugs). (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Angela R. Ozburn, Amanda M. Barkley-Levenson, Pamela Metten, John C. Crabbe Source Type: research
DNA methylation patterns at prodynorphin gene promoter in alcoholism
Dynorphins are critically involved in the development, maintenance and relapse of alcoholism. Alcohol-induced changes in the prodynorphin gene expression may be influenced by both gene polymorphisms and epigenetic modifications. The present study of human alcoholics aims to evaluate DNA methylation patterns in the prodynorphin gene (PDYN) promoter and to identify single nucleotide polymorphisms (SNPs) that are associated with alcohol dependence and with altered DNA methylation. Genomic DNA was isolated from peripheral blood cells of alcoholics and healthy controls, and DNA methylation was studied in the PDYN promoter by bi...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Claudio D'Addario, Klementy Shchetynsky, Mariangela Pucci, Carlo Cifani, Agneta Gunnar, Vladana Vukojevi ć, Leonid Padyukov, Lars Terenius Source Type: research
RNA-sequencing reveals astrocyte transcriptome alterations in response to chronic ethanol exposure
Astrocytes are critical for maintaining homeostasis and proper brain functioning, and have recently been identified as active contributors to information processing. While many studies have shown that astrocyte phenotype is altered by chronic alcohol consumption, it is unknown how alcohol exposure affects the astrocyte transcriptome and molecular function. Whole tissue human and mouse datasets from our lab point to a potential role for astrocytes in the brain ’s response to alcohol abuse, however it is still difficult to separate astrocyte-specific changes in vivo from those occurring in other cells. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: E.K. Erickson, S.P. Farris, Y.A. Blednov, R.D. Mayfield, R.A. Harris Source Type: research
Genomic signature of PPAR agonists in mouse amygdala: Role in alcohol consumption
PPARs are nuclear hormone receptors that act as ligand-activated transcription factors. PPAR agonists are used to treat hyperlipidemia and diabetes, and are neuroprotective, hepatoprotective and decrease nicotine and alcohol self-administration. We used an unbiased genomic screen to characterize the gene expression profile induced in the mouse amygdala, a key brain region for alcohol dependence, by two PPAR agonists that are effective (fenofibrate and tesaglitazar) and one that is non-effective (bezafibrate) at reducing alcohol consumption. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: L.B. Ferguson, Y.A. Blednov, R.A. Harris Source Type: research
