Cross-species convergence in the genetics of ethanol response and alcohol dependence
Despite the substantial challenges in identifying specific genes influencing alcohol dependence risk, alcohol-related phenotypes have some critical advantages for gene identification. Ethanol has been in the environment since the evolution of micro-organisms, and pathways and genes mediating ethanol response are highly conserved across species. To exploit this conservation, well-developed experimental approaches exist to test directly whether changes in candidate genes impact behavioral response to ethanol in a variety of model organisms, providing a critical means to demonstrate the functional role of candidate genes in e...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: J.C. Bettinger, M.S. Bowers, M. Grotewiel, K.S. Kendler, M.F. Miles, V.I. Vladimirov, B.T. Webb, B.P. Riley Source Type: research
Systems genetics of substance use disorders: Resources, methods, challenges, successes
Our research communities are generating an overwhelming variety and volume of data on alcoholism and addiction. Single studies using RNA-seq and Drop-seq now generate from 100 to 50,000 transcriptomes (Mulligan et al., 2016, Macosko et al. 2015, PMID 26000488). We need far better resources and tools to assemble, analyze, and integrate massive and heterogenous data sets. We also need to be able to exploit data to test hypotheses and mechanisms. With support of NIAAA and NIDA we have assembled an open source web portal for addictome research that includes expression data sets and curated phenotypes and outcome measurements f...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Robert W. Williams Source Type: research
Brain transcriptional changes in the mouse and macaque associated with excessive ethanol consumption
Extensive data are now available for the transcriptional features associated with the risk of developing and/or the consequences of excessive ethanol consumption and withdrawal. Data have been collected in flies, mouse, rat, macaque and human samples. One assumes that there will be conservation of these transcriptional features. Here we examine a subset of these data focusing on mice selectively bred from heterogeneous stock (HS) for ethanol preference (2-bottle choice) or for high drinking in the dark (HDID) and on both rhesus and cynomolgus macaques chronically exposed to ethanol (choice consumption). (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: R. Hitzemann, O. Iancu, A. Colville, P. Darakjian, D. Oberbeck, N. Walter, S. McWeeney, C. Zheng, J. Daunais, John Crabbe, P. Metten, K. Grant Source Type: research
Forced swim stress-escalated alcohol drinking and BNST kappa opioid receptors
The neuropeptide dynorphin (DYN) acting on kappa opioid receptors (KORs) has been recently studied for treating alcohol abuse and stress disorders. The current experiments explored the role of central DYN and KORs after forced swim stress in adult mice given intermittent access to alcohol. After 8 weeks of heavy drinking, repeated swim stress generated a latent increase in voluntary alcohol consumption without affecting H2O intake. The KOR antagonist nor-binaltrophimine significantly suppressed the high-level alcohol drinking in both stressed and non-stressed mice, with greater reductions in the stressed animals. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Lara S. Hwa, Tom Kash Source Type: research
Chemogenetic and optogenetic control of excessive alcohol drinking through inactivation of a neuronal ensemble in the central nucleus of the amygdala
A neuronal ensemble in the central nucleus of the amygdala (CeA) that is recruited in anticipation of alcohol binge drinking has been recently identified but causal evidence that this “binge-drinking” neuronal ensemble is responsible for alcohol binge drinking is lacking. Moreover, unknown is whether a “dependence” neuronal ensemble can also be identified in the CeA in dependent rats and whether this hypothetical dependence neuronal ensemble is responsible for compulsive- like alcohol drinking in dependent rats. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Olivier George Source Type: research
CRF modulation in VTA-DRN escalates alcohol intake after social stress
Victims of aggression undergo neuroadaptive changes that escalate alcohol self-administration in rodent models of drug abuse. CRF modulation of microcircuits comprising control from the mPFC to VTA and DRN are candidate mechanisms for these long-lasting neuroadaptations. Our hypothesis examines the role of extra-hypothalamic CRF in victims of aggression who consume large amounts of alcohol. Pharmacogenetic and optogenetic challenges and microdialysis point to a critical role of CRF modulation of DA in the VTA. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Klaus A. Miczek Source Type: research
Social isolation stress increases kappa opioid receptor function on dopamine terminals in the nucleus accumbens of rats
Adverse social experiences, especially during adolescence, increase the risk of developing alcohol use disorders during adulthood in humans. Similarly, rats reared in social isolation during adolescence show greater ethanol intake in adulthood compared to group housed controls. Acute stress elevates dynorphin levels, a kappa opioid receptor (KOR) ligand, which regulates dopamine. Activation of KORs inhibits DA release in the NAc. The NAc plays an integral role in the neurobiology of stress, anxiety, and reward-seeking behavior. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Anushree N. Karkhanis, Deborah Leussen, Jeffrey L. Weiner, Rong Chen, Sara R. Jones Source Type: research
Synaptic plasticity, optogenetics and emerging treatments against substance use disorders
The most recent work from my laboratory has used a combination of electrophysiology, optogenetic, molecular and behavioral procedures to keep on studying the basic cellular mechanisms and circuits underlying reward and substance use disorders. During my presentation, I will highlight the most recent discoveries from my laboratory. Furthermore, I will discuss the status of optogenetic-based brain stimulation treatments against substance use disorders. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Antonello Bonci Source Type: research
Functional and pharmacological MRI in drug and alcohol addiction: A translational perspective
Alcohol abuse has been associated with long-term changes in functional, metabolic and morphometric parameters as measured by neuroimaging methods in patients. These changes include reduced grey matter volume in cortical and limbic regions, reduced resting state metabolism and connectivity, and abnormal functional responses in the reward and stress systems. An unanswered question in alcohol research is whether these alterations are the sole consequence of chronic alcohol use, or contain heritable contributions reflecting biological propensity toward ethanol addiction. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Angelo Bifone Source Type: research
Development of functional and structural brain alterations in logitudinal models of high alcohol consumption and abstinence
Alterations in brain structure and function have been repeatedly reported for a number of neurologic and psychiatric conditions using non-invasive imaging measures. However, the extent to which these techniques can longitudinally follow the evolution of a pathological state, and its treatment, is not clear. We hypothesize that sensing the microstructural properties of brain parenchyma with multimodal magnetic resonance imaging (MRI), and combining the extracted features with machine learning classifiers, might provide a strong analytical framework to identify states in brain pathologies. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Úrsula Pérez, Alejandro Cosa, Laura Pérez-Cervera, Roberto Ciccocioppo, Wolfgang Sommer, David Moratal, Santiago Canals Source Type: research
Translational FDG-PET studies in alcohol and cocaine addicted rats
[18F]-FDG PET studies in alcoholics have consistently reported decreases in overall brain glucose metabolism at rest and following acute alcohol administration. However, the time course of cerebral glucose utilization in the transition to addictive behavior is not known and requires longitudinal translational imaging studies in animal models of alcoholism. Here, we studied brain glucose uptake in a DSM-based animal model of alcohol addiction under rest and following alcohol exposure. Acute alcohol administration significantly reduced the whole-brain glucose metabolism in rats. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: R. Spanagel, N. Cannella, V. Vengeliene, A. Cosa-Linan, T. Takahashi Source Type: research
Interactions of early-life stress and prenatal alcohol exposure on executive control
There is growing consensus that moderate alcohol intake during pregnancy can lead to lasting cognitive impairments. These impairments, categorized as Fetal Alcohol Spectrum Disorder (FASD) are characterized by deficits in working memory, response inhibition, and behavioral flexibility. However, the clinical course is influenced by multiple factors, including early life environments. A communal nest, in which multiple dams are housed together prior to parturition and share a nest with subsequent litters, increases multiple measures of pup-care. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Rebecca Castillo, K. Caldwell, J.L. Brigman Source Type: research
Co-occurring maternal depression and prenatal alcohol exposure: Multimodal MRI findings in the infant brain
Alcohol use and alcohol use disorders contribute a significant proportion of the burden of disease in low, middle, and high-income countries. Maternal mental health disorders are common co-occurring problems in these populations. For neurodevelopmental disorders, studies have consistently shown that early intervention leads to better long-term outcomes. But early intervention is predicated on early detection and targeted interventions. Understanding the core areas of susceptibility to prenatal alcohol effects with and without comorbid maternal depression as they manifest in early life is key to developing strategies for ea...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Kirsty Donald Source Type: research
Prenatal alcohol exposure: Fetal programming, alcohol-stress interactions, and sex differences in outcome
Fetal alcohol spectrum disorder (FASD) is an umbrella term encompassing the range of adverse effects resulting from prenatal alcohol exposure (PAE). Alcohol not only has direct effects on the developing fetal brain and organ systems, but also indirect effects through changes in maternal endocrine function and altered maternal-fetal hormonal interactions, with significant impacts on fetal neurobiological, metabolic, physiological and behavioral functions. The hypothalamic-pituitary-adrenal (HPA) axis, a key component of the stress system, is highly sensitive to programming during fetal and neonatal development. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Joanne Weinberg, Charlis Raineki, Tamara Bodnar, Ni Lan, Kristina Uban, Vivian Lam, Kim Hellemans Source Type: research
Choline supplementation attenuates severity of hippocampal BDNF reductions caused by developmental alcohol exposure
Prenatal alcohol exposure alters physical and neurological development, adversely affecting long-term behavior and health. Early nutritional variables are among the factors that can modify ethanol ’s teratogenic effects. We have shown that supplementation with the nutrient choline can attenuate ethanol’s adverse effects on behaviors that depend on the functional integrity of the hippocampus, even when administered after alcohol exposure has ceased. However, it is not fully understood how choline reduces the severity of ethanol’s effects on hippocampal development. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: J.D. Thomas, K. Potter Source Type: research
