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(Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Source Type: research
Schedule
(Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Source Type: research
Stress, negative reinforcement and compulsive drug seeking
Compulsive alcohol seeking can derive from 3 multiple sources that comprise neuroadaptations in the 3 stages of the addiction cycle binge/intoxication stage, withdrawal/negative affect stage, and preoccupation-anticipation ( “craving”) stage. A powerful driving force in both the withdrawal/negative affect and preoccupation-anticipation stages in alcohol use disorders is the construct of negative reinforcement, defined here as drug taking that alleviates a negative emotional state created by drug abstinence. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: George F. Koob Tags: Plenary lectures Source Type: research
Habitual behavior in addiction & stress: Neurogenetic approaches to PTSD comorbidity
Exposure to traumatic experiences, especially those occurring in childhood, has been linked to substance use disorders (SUDs), including abuse and dependence. Childhood and adult trauma, as well as SUDs, are also highly associated with Posttraumatic Stress Disorder (PTSD) and other mood-related psychopathology. I will examine the relationships between trauma, substance use, and PTSD, as well as markers of resilience, in a sample of urban primary care patients. Further we examine genetic polymorphisms that appear to be associated with increased risk for both disorders, and neural circuit activity associated with risk for bo...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Kerry Ressler Source Type: research
Sex differences in animal models: Focus on stress and addiction
Addiction is characterized by compulsive drug taking that supersedes other recreational, occupational or social pursuits. Sex differences are seen in the motivation to take drugs of abuse and in the escalation of drug taking behavior and stress can differentially affect drug-taking behaviors in males vs. females. Using the rat as an animal model, we find that in females there are rapid effects of estradiol on the ascending dopamine system that enhance the female ’s motivation to engage in these behaviors. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Jill B. Becker Source Type: research
An endocannabinoid mechanism promoting resilience to traumatic stress
Stress is a major risk factor for the development of affective disorders including major depression and posttraumatic stress disorder, and relapse to alcohol use during abstinence. Understanding the neurobiological mechanisms conferring resilience to the adverse consequences of stress could have broad implications for the treatment of anxiety disorders and alcohol use disorders. We utilized inter-individual differences in stress-susceptibility to demonstrate a critical role for the endogenous cannabinoid 2-arachidonoylglycerol (2-AG) in stress-resilience. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Rebecca J. Bluett, Rita B áldi, Andre Haymer, Nolan D. Hartley, Andrew Gaulden, David Marcus, Ramzi Mardam-Bey, Brian C. Shonesy, Jashim Uddin, Lawrence J. Marnett, Roger J. Colbran, Danny G. Winder, Sachin Patel Tags: Symposia Source Type: research
Endocannabinoid signaling in the amygdala and the regulation of fear and anxiety: Not always a clear path
Endocannabinoid (eCB) signaling in the amygdala appears to be critical for the regulation of stress, fear and anxiety. Exposure to stress causes a rapid induction of the enzyme fatty acid amide hydrolase (FAAH), which results in an accelerated metabolism of the eCB ligand anandamide (AEA), through a CRH-dependent mechanism, resulting in a decline in AEA signaling. Consistent with this, inhibition of FAAH appears to be able to reduce the increase in anxiety that is seen following elevations in amygdalar CRH signaling or following exposure to frank stressors. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Matthew N. Hill Source Type: research
Imaging the endocannabinoid system after acute, chronic alcohol abuse and monitored abstinence
Recent biochemical and preclinical evidence suggests involvement of the endocannabinoid signaling system in alcohol use disorders. The main objective of our work was to investigate the effect of a binge drinking episode and chronic alcohol consumption on CB1R availability, using positron emission tomography (PET) imaging radioligand, both in humans and animal models. Firstly, twenty healthy drinkers underwent [18F]MK-9470 PET at baseline and after intravenous ethanol administration. Acute alcohol administration resulted in a global increase of CB1R availability (+15.8%), throughout all grey matter regions, that was inverse...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Jenny Ceccarini, Cindy Casteels, Guy Bormans, Stephan Claes, Koen Van Laere Source Type: research
Diacylglycerol lipase disinhibits VTA dopamine neurons during chronic nicotine exposure
Chronic nicotine exposure (CNE) alters synaptic transmission in the ventral tegmental area (VTA) in a manner that enhances dopaminergic signaling and promotes nicotine use. The present experiments identify a correlation between enhanced production of the endogenous cannabinoid 2-arachidonoylglycerol (2-AG) and diminished release of the inhibitory neurotransmitter GABA in the VTA following CNE. To study the functional role of on-demand 2-AG signaling in GABAergic synapses, we used 1,2,3-triazole urea compounds to selectively inhibit 2-AG biosynthesis by diacylglycerol lipase (DAGL). (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Matthew W. Buczynski, Melissa A. Herman, Ku-Lung Hsu, Luis A. Natividad, Cristina Irimia, Ilham Y. Polis, Holly Pugh, Jae Won Chang, Micah J. Niphakis, Benjamin F. Cravatt, Marisa Roberto, Loren H. Parsons Source Type: research
Adolescent alcohol exposure, epigenetic reprogramming and adult psychopathology
Adolescent binge drinking appears to be an important risk factor for psychiatric disorders including alcoholism later in life. We investigated the role of histone methylation mechanisms in adolescent intermittent ethanol (AIE) exposure-induced anxiety-like behaviors in adulthood. Male rats were exposed to intermittent ethanol or n-saline (AIS) during post-natal days (PND) 28-41 and allowed to grow to adulthood (PND 92-102). AIE rats displayed anxiety-like behavior in adulthood. AIE increased H3K27 trimethylation (H3K27me3) and decreased KDM6B occupancy at the activity regulated cytoskeletal-associated protein (Arc) gene in...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Subhash C. Pandey, Evan J. Kyzar, Dadasaheb M. Kokare, Tara Teppen, Huaibo Zhang Source Type: research
Preconception alcohol increases offspring vulnerability to stress via epigenetic programming
The effect of preconception drinking by the mother on the life-long health outcomes of her babies is not known, and therefore, in this study using an animal model, we determined the impact of preconception alcohol drinking of the mother on offspring stress response during adult hood. Preconception alcohol exposures involved feeding adult female rats with 6.7% alcohol in their diet for 4 weeks, went without alcohol for 3 weeks and were bred to generate male and female offspring. Preconception alcohol exposed offspring ’s birth weight, body growth, stress response, immune function, anxiety-like behaviors and changes in str...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Dipak K. Sarkar, Shaima Jabbar, Lucy G. Chastain, Omkaram Gangisetty, Miguel A. Cabrera, Kamil Sochacki Source Type: research
Efficacy of HDAC1 inhibitors in a new model of binge drinking in rats
New strategies for the treatment of alcohol dependence are a pressing need, and recent evidence suggests that targeting enzymes involved in epigenetic mechanisms seems to have great potential. Among these mechanisms, alteration of histone acetylation by histone deacetylases is of great importance for gene expression and has also been implicated in addiction. Binge drinking is a major concern in the field of alcohol addiction not only because it is a dangerous behaviour but also because it may also be the gateway to addictive behaviour. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: J. Jeanblanc, M.D.C. Gonzalez Marin, S. Lebourgeois, R. Legastelois, M. Naassila Source Type: research
mTORC1 is a key molecular transducer of alcohol-dependent plasticity, seeking and relapse
The serine and threonine kinase mammalian target of rapamycin in complex 1 (mTORC1) controls the translation of a subset of mRNAs. In the adult brain, mTORC1 plays an important role in synaptic plasticity and memory by activating the translational machinery at dendrites. We previously discovered that excessive alcohol intake activates mTORC1 in the nucleus accumbens (Nac) of rodents. We further showed that mTORC1 plays an important role in the mechanisms that underlie the development and maintenance of excessive alcohol consumption as well as the reconsolidation of alcohol seeking memories. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Dorit Ron Source Type: research
Strong beta-arrestin signaling may cause unwanted effects for drug treatments of alcohol use disorders
Alcohol use disorder (AUD) is defined as a chronic, relapsing brain disease which carries a large socioeconomic burden; it is estimated that 17 million adults in the United States suffer from AUD. The delta opioid receptors (DORs) are an exciting new target for treatment of AUD as activation of DORs can not only reduce alcohol intake, but can also reduce anxiety and depression, which are often co-morbid with AUD. We have recently identified that the ability of DOR agonist to modulate alcohol consumption in mice is tightly correlated with a DOR agonist ’s ability to recruit β-arrestin2, a protein involved in both recepto...
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Richard M. van Rijn, Terrance Chiang, Rob J. Cassell, Kendall L. Mores, Mohamed S.A. El-Sayed, Mark S. Cushman, Amr H.A. Abdallah, Markus A. Lill Source Type: research
ALK regulates binge alcohol consumption and dopamine D2 receptor trafficking
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase associated with alcohol dependence in humans and behavioral responses to ethanol in mice. We found that the ALK inhibitors TAE684 and alectinib decrease ethanol consumption by mice in the drinking in the dark (DID) protocol. Since the ventral tegmental area (VTA) is involved in binge ethanol consumption, we determined whether ALK expression in the VTA is important for this behavior. Mice expressing a short hairpin RNA (shRNA) targeting ALK in the VTA drank less ethanol compared with controls. (Source: Alcohol)
Source: Alcohol - May 1, 2017 Category: Addiction Authors: Amy W. Lasek, Donghong He, Hu Chen, John W. Dutton, Chang You, Mark S. Brodie Source Type: research
