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https://www.readbyqxmd.com/read/28531265/utility-of-nonhuman-primates-in-substance-use-disorders-research
#1
Matthew L Banks, Paul W Czoty, Sidney S Negus
Substance use disorders (i.e., drug addiction) constitute a global and insidious public health issue. Preclinical biomedical research has been invaluable in elucidating the environmental, biological, and pharmacological determinants of drug abuse and in the process of developing innovative pharmacological and behavioral treatment strategies. For more than 70 years, nonhuman primates have been utilized as research subjects in biomedical research related to drug addiction. There are already several excellent published reviews highlighting species differences in both pharmacodynamics and pharmacokinetics between rodents and nonhuman primates in preclinical substance abuse research...
May 20, 2017: ILAR Journal
https://www.readbyqxmd.com/read/28523977/the-application-of-deep-brain-stimulation-in-the-treatment-of-psychiatric-disorders
#2
Ilse Graat, Martijn Figee, Damiaan Denys
Deep brain stimulation (DBS) is a last-resort treatment for neurological and psychiatric disorders that are refractory to standard treatment. Over the last decades, the progress of DBS in psychiatry has been slower than in neurology, in part owing to the heterogenic symptomatology and complex neuroanatomy of psychiatric disorders. However, for obsessive-compulsive disorder (OCD) DBS is now an accepted treatment. This study first reviews clinical outcomes and mechanisms of DBS for OCD, and then discusses these results in an overview of current and future psychiatric applications, including DBS for mood disorders, Tourette's syndrome, addiction, anorexia nervosa, autism, schizophrenia, and anxiety disorders...
April 2017: International Review of Psychiatry
https://www.readbyqxmd.com/read/28523558/epigenome-editing-in-the-brain
#3
Pavel Bashtrykov, Albert Jeltsch
Epigenome editing aims for an introduction or removal of chromatin marks at a defined genomic region using artificial EpiEffectors resulting in a modulation of the activity of the targeted functional DNA elements. Rationally designed EpiEffectors consist of a targeting DNA-binding module (such as a zinc finger protein, TAL effector, or CRISPR/Cas complex) and usually, but not exclusively, a catalytic domain of a chromatin-modifying enzyme. Epigenome editing opens a completely new strategy for basic research of the central nervous system and causal treatment of psychiatric and neurological diseases, because rewriting of epigenetic information can lead to the direct and durable control of the expression of disease-associated genes...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28521782/combining-alcohol-interventions-with-tobacco-addictions-treatment-in-primary-care-the-combat-study-a-pragmatic-cluster-randomized-trial
#4
Nadia Minian, Dolly Baliunas, Laurie Zawertailo, Aliya Noormohamed, Norman Giesbrecht, Christian S Hendershot, Bernard Le Foll, Jürgen Rehm, Andriy Samokhvalov, Peter L Selby
BACKGROUND: Tobacco and alcohol use present multiplicative risk for aerodigestive cancers. Reducing alcohol consumption improves smoking cessation outcomes and reduces cancer risk. Risky alcohol consumption and smoking are often treated separately despite concurrent treatment potentially leading to better outcomes for each. However, no rapidly scalable program exists for combined interventions in primary care clinics spread across wide geographic areas. This cluster randomized trial aims to report on the effects of a novel clinical decision support system (CDSS) on intervention rates by primary care practitioners addressing risky alcohol use in a smoking cessation program...
May 18, 2017: Implementation Science: IS
https://www.readbyqxmd.com/read/28516124/bioinformatic-analysis-for-profiling-drug-induced-chromatin-modification-landscapes-in-mouse-brain-using-chlp-seq-data
#5
Yong-Hwee Eddie Loh, Jian Feng, Eric Nestler, Li Shen
Chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-seq) is a powerful technology to profile genome-wide chromatin modification patterns and is increasingly being used to study the molecular mechanisms of brain diseases such as drug addiction. This protocol discusses the typical procedures involved in ChIP-seq data generation, bioinformatic analysis, and interpretation of results, using a chronic cocaine treatment study as a template. We describe an experimental design that induces significant chromatin modifications in mouse brain, and the use of ChIP-seq to derive novel information about the chromatin regulatory mechanisms involved...
February 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28507002/neuregulin-1-allosterically-enhances-the-anti-tumor-effects-of-the-non-competing-anti-her3-antibody-9f7-f11-by-increasing-its-binding-to-her3
#6
Christophe Le Clorennec, Hervé Bazin, Olivier Dubreuil, Christel Larbouret, Charline Ogier, Yassamine Lazrek, Veronique Garambois, Marie-Alix Poul, Philippe Mondon, Jean-Marc Barret, Gérard Mathis, Jean-François Prost, André Pèlegrin, Thierry Chardès
Exploratory clinical trials using therapeutic anti-HER3 antibodies strongly suggest that neuregulin (NRG1; HER3 ligand) expression at tumor sites is a predictive biomarker of anti-HER3 antibody efficacy in cancer. We hypothesized that in NRG1-expressing tumors, where the ligand is present before antibody treatment, anti-HER3 antibodies that do not compete with NRG1 for receptor binding have a higher receptor-neutralizing action than antibodies competing with the ligand for binding to HER3. Using time resolved-fluorescence energy transfer (TR-FRET), we demonstrated that in the presence of recombinant NRG1, binding of 9F7-F11 (a non-ligand competing anti-HER3 antibody) to HER3 is increased, whereas that of ligand-competing anti-HER3 antibodies (H4B-121, U3-1287, Ab#6, Mab205...
May 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28502978/the-opioid-receptor-triple-agonist-dpi-125-produces-analgesia-with-less-respiratory-depression-and-reduced-abuse-liability
#7
Shou-Pu Yi, Qing-Hong Kong, Yu-Lei Li, Chen-Ling Pan, Jie Yu, Ben-Qiang Cui, Ying-Fei Wang, Guan-Lin Wang, Pei-Lan Zhou, Li-Li Wang, Ze-Hui Gong, Rui-Bin Su, Yue-Hai Shen, Gang Yu, Kwen-Jen Chang
Opioid analgesics remain the first choice for the treatment of moderate to severe pain, but they are also notorious for their respiratory depression and addictive effects. This study focused on the pharmacology of a novel opioid receptor mixed agonist DPI-125 and attempted to elucidate the relationship between the δ-, μ- and κ-receptor potency ratio and respiratory depression and abuse liability. Five diarylmethylpiperazine compounds (DPI-125, DPI-3290, DPI-130, KUST202 and KUST13T02) were selected for this study...
May 15, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28501092/emerging-novel-therapeutic-agents-in-the-treatment-of-patients-with-gastroesophageal-and-gastric-adenocarcinoma
#8
REVIEW
Gayathri Anandappa, Ian Chau
With further understanding of the biology of gastric and gastroesophageal adenocarcinomas, strides are being made to find effective treatments through novel trial designs. This article focuses on the ongoing trials of drugs targeting specific hallmarks of gastric and gastroesophageal cancers, including oncogene addiction proliferative pathways (fibroblast growth factor receptor 2 amplified tumors), stem cell inhibition, apoptotic induction through claudin inhibitors, and matrix metalloproteinase inhibition...
June 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/28499916/effects-of-neonatal-and-adolescent-neuroactive-steroid-manipulation-on-locomotor-activity-induced-by-ethanol-in-male-wistar-rats
#9
Iris Bartolomé, Anna Llidó, Sònia Darbra, Marc Pallarès
Neonatal neuroactive steroids levels are crucial for brain development. Alterations of neonatal neuroactive steroids levels induce anxiolytic-like effects and improve exploration in novel environments in adulthood. These behavioural traits, i.e. sensation/novelty seeking, anxiety or impulsivity, are associated with vulnerability to drug use and abuse. Adolescence is also recognized as a particularly critical developmental phase to contribute to vulnerable phenotype. However, the influence of neuroactive steroids during development in the vulnerability to drug addiction has been poorly studied...
May 9, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28498560/deletion-of-%C3%AE-5-nicotine-receptor-subunits-abolishes-nicotinic-aversive-motivational-effects-in-a-manner-that-phenocopies-dopamine-receptor-antagonism
#10
Taryn E Grieder, Olivier George, Mandy Yee, Michael A Bergamini, Michal Chwalek, Geith Maal-Bared, Hector Vargas-Perez, Derek van der Kooy
Nicotine addiction is a worldwide epidemic that claims millions of lives each year. Genetic deletion of α5 nicotinic acetylcholine receptor (nAChR) subunits has been associated with increased nicotine intake, however, it remains unclear whether acute nicotine is less aversive or more rewarding, and whether mice lacking the α5 nAChR subunit can experience withdrawal from chronic nicotine. We used place conditioning and conditioned taste avoidance paradigms to examine the effect of α5 subunit-containing nAChR deletion (α5 -/-) on conditioned approach and avoidance behaviour in nondependent and nicotine-dependent and -withdrawn mice, and compared these motivational effects with those elicited after dopamine receptor antagonism...
May 12, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28491027/post-learning-sleep-transiently-boosts-context-specific-operant-extinction-memory
#11
Margarita Borquez, María P Contreras, Ennio Vivaldi, Jan Born, Marion Inostroza
Operant extinction is learning to supress a previously rewarded behavior. It is known to be strongly associated with the specific context in which it was acquired, which limits the therapeutic use of operant extinction in behavioral treatments, e.g., of addiction. We examined whether sleep influences contextual memory of operant extinction over time, using two different recall tests (Recent and Remote). Rats were trained in an operant conditioning task (lever press) in context A, then underwent extinction training in context B, followed by a 3-h retention period that contained either spontaneous morning sleep, morning sleep deprivation, or spontaneous evening wakefulness...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28487202/thalamic-mast-cell-activity-is-associated-with-sign-tracking-behavior-in-rats
#12
Christopher J Fitzpatrick, Jonathan D Morrow
Mast cells are resident immune cells in the thalamus that can degranulate and release hundreds of signaling molecules (i.e., monoamines, growth factors, and cytokines) both basally and in response to environmental stimuli. Interestingly, mast cell numbers in the brain show immense individual variation in both rodents and humans. We used a Pavlovian conditioned approach (PCA) procedure to examine whether mast cells are associated with individual variation in the attribution of incentive-motivational value to reward-related cues...
May 6, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28485671/biased-and-less-sensitive-a-gamified-approach-to-delay-discounting-in-heroin-addiction
#13
Stefan Scherbaum, Paul Haber, Kirsten Morley, Dylan Underhill, Ahmed A Moustafa
INTRODUCTION: People with addiction will continue to use drugs despite adverse long-term consequences. We hypothesized (a) that this deficit persists during substitution treatment, and (b) that this deficit might be related not only to a desire for immediate gratification, but also to a lower sensitivity for optimal decision making. We investigated how individuals with a history of heroin addiction perform (compared to healthy controls) in a virtual reality delay discounting task. This novel task adds to established measures of delay discounting an assessment of the optimality of decisions, especially in how far decisions are influenced by a general choice bias and/or a reduced sensitivity to the relative value of the two alternative rewards...
May 9, 2017: Journal of Clinical and Experimental Neuropsychology
https://www.readbyqxmd.com/read/28481178/psilocybin-assisted-therapy-a-review-of-a-novel-treatment-for-psychiatric-disorders
#14
Kelan Thomas, Benjamin Malcolm, Dan Lastra
Recent research suggests that functional connectivity changes may be involved in the pathophysiology of psychiatric disorders. Hyperconnectivity in the default mode network has been associated with psychopathology, but psychedelic serotonin agonists like psilocybin may profoundly disrupt these dysfunctional neural network circuits and provide a novel treatment for psychiatric disorders. We have reviewed the current literature to investigate the efficacy and safety of psilocybin-assisted therapy for the treatment of psychiatric disorders...
May 8, 2017: Journal of Psychoactive Drugs
https://www.readbyqxmd.com/read/28466871/reversal-of-cocaine-associated-synaptic-plasticity-in-prefrontal-cortex
#15
James M Otis, Devin Mueller
Addiction is characterized by abnormalities in prefrontal cortex that are thought to allow drug-associated cues to drive compulsive drug seeking and taking. Identification and reversal of these pathologic neuroadaptations is therefore critical for treatment of addiction. Previous studies using rodents reveal that drugs of abuse cause dendritic spine plasticity in prelimbic medial prefrontal cortex (PL-mPFC) pyramidal neurons, a phenomenon that correlates with the strength of drug-associated memories in vivo...
May 3, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28462472/role-of-the-agranular-insular-cortex-in-contextual-control-over-cocaine-seeking-behavior-in-rats
#16
Amy A Arguello, Rong Wang, Carey M Lyons, Jessica A Higginbotham, Matthew A Hodges, Rita A Fuchs
RATIONALE: Environmental stimulus control over drug relapse requires the retrieval of context-response-cocaine associations, maintained in long-term memory through active reconsolidation processes. Identifying the neural substrates of these phenomena is important from a drug addiction treatment perspective. OBJECTIVES: The present study evaluated whether the agranular insular cortex (AI) plays a role in drug context-induced cocaine-seeking behavior and cocaine memory reconsolidation...
May 2, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28441678/the-addiction-recovery-clinic-a-novel-primary-care-based-approach-to-teaching-addiction-medicine
#17
Stephen R Holt, Nora Segar, Dana A Cavallo, Jeanette M Tetrault
PROBLEM: Substance use is highly prevalent in the United States, but little time in the curriculum is devoted to training internal medicine residents in addiction medicine. APPROACH: In 2014, the authors developed and launched the Addiction Recovery Clinic (ARC) to address this educational gap while also providing outpatient clinical services to patients with substance use disorders. The ARC is embedded within the residency primary care practice and is staffed by three to four internal medicine residents, two board-certified addiction medicine specialists, one chief resident, and one psychologist...
May 2017: Academic Medicine: Journal of the Association of American Medical Colleges
https://www.readbyqxmd.com/read/28436446/opioid-self-administration-is-attenuated-by-early-life-experience-and-gene-therapy-for-anti-inflammatory-il-10-in-the-nucleus-accumbens-of-male-rats
#18
Michael J Lacagnina, Ashley M Kopec, Stewart S Cox, Richa Hanamsagar, Corinne Wells, Susan Slade, Peter M Grace, Linda R Watkins, Edward D Levin, Staci D Bilbo
Early-life conditions can contribute to the propensity for developing neuropsychiatric disease, including substance abuse disorders. However, the long-lasting mechanisms that shape risk or resilience for drug addiction remain unclear. Previous work has shown that a neonatal handling procedure in rats (which promotes enriched maternal care) attenuates morphine conditioning, reduces morphine-induced glial activation, and increases microglial expression of the anti-inflammatory cytokine interleukin-10 (IL-10)...
April 24, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28433417/mechanistic-insights-into-epigenetic-modulation-of-ethanol-consumption
#19
Igor Ponomarev, Claire E Stelly, Hitoshi Morikawa, Yuri A Blednov, R Dayne Mayfield, R Adron Harris
There is growing evidence that small-molecule inhibitors of epigenetic modulators, such as histone deacetylases (HDAC) and DNA methyltransferases (DNMT), can reduce voluntary ethanol consumption in animal models, but molecular and cellular processes underlying this behavioral effect are poorly understood. We used C57BL/6J male mice to investigate the effects of two FDA-approved drugs, decitabine (a DNMT inhibitor) and SAHA (an HDAC inhibitor), on ethanol consumption using two tests: binge-like drinking in the dark (DID) and chronic intermittent every other day (EOD) drinking...
May 2017: Alcohol
https://www.readbyqxmd.com/read/28429582/obesity-and-addiction-can-a-complication-of-surgery-help-us-understand-the-connection
#20
REVIEW
V Ivezaj, L E Stoeckel, N M Avena, S C Benoit, A Conason, J F Davis, A N Gearhardt, R Goldman, J E Mitchell, C N Ochner, K K Saules, K J Steffen, E Stice, S Sogg
Obesity is a multifactorial, chronic disease that has proven difficult to treat. An increased understanding of aetiological mechanisms is critical to the development of more effective obesity prevention and treatment strategies. A growing body of empirical evidence has demonstrated parallels between obesity, overeating and substance abuse, including shared behavioural, psychological and neurophysiological factors implicated in the excessive intake of both food and substances of abuse. Several different lines of research have recently emerged that hold the potential to shed light on the connection between obesity, food reward and addiction, with studies examining changes in alcohol use/misuse after weight loss surgery providing a particularly interesting perspective on these interrelationships...
April 21, 2017: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
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