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https://www.readbyqxmd.com/read/28544993/muscarinic-receptor-m4-positive-allosteric-modulators-attenuate-central-effects-of-cocaine
#1
Camilla Dall, Pia Weikop, Ditte Dencker, Anna C Molander, Gitta Wörtwein, P Jeffrey Conn, Anders Fink-Jensen, Morgane Thomsen
BACKGROUND: Cocaine addiction is a chronic brain disease affecting neurotransmission. Muscarinic cholinergic receptors modulate dopaminergic signaling in the reward system, and muscarinic receptor stimulation can block direct reinforcing effects of cocaine. Here, we tested the hypothesis that specific muscarinic M4 receptor stimulation can attenuate the discriminative stimulus effects and conditioned rewarding effects of cocaine, measures believed to predict the ability of cocaine and cocaine-associated cues to elicit relapse to drug taking...
May 16, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28541119/treatment-of-opioid-use-disorder-with-ibogaine-detoxification-and-drug-use-outcomes
#2
Thomas Kingsley Brown, Kenneth Alper
BACKGROUND: Ibogaine is a monoterpene indole alkaloid used in medical and nonmedical settings for the treatment of opioid use disorder. Its mechanism of action is apparently novel. There are no published prospective studies of drug use outcomes with ibogaine. OBJECTIVES: To study outcomes following opioid detoxification with ibogaine. METHODS: In this observational study, 30 subjects with DSM-IV Opioid Dependence (25 males, 5 females) received a mean total dose of 1,540 ± 920 mg ibogaine HCl...
May 25, 2017: American Journal of Drug and Alcohol Abuse
https://www.readbyqxmd.com/read/28539894/modulation-of-brain-activity-with-noninvasive-transcranial-direct-current-stimulation-tdcs-clinical-applications-and-safety-concerns
#3
REVIEW
Haichao Zhao, Lei Qiao, Dongqiong Fan, Shuyue Zhang, Ofir Turel, Yonghui Li, Jun Li, Gui Xue, Antao Chen, Qinghua He
Transcranial direct current stimulation (tDCS) is a widely-used tool to induce neuroplasticity and modulate cortical function by applying weak direct current over the scalp. In this review, we first introduce the underlying mechanism of action, the brief history from discovery to clinical scientific research, electrode positioning and montages, and parameter setup of tDCS. Then, we review tDCS application in clinical samples including people with drug addiction, major depression disorder, Alzheimer's disease, as well as in children...
2017: Frontiers in Psychology
https://www.readbyqxmd.com/read/28534313/class-based-chronicities-of-suffering-and-seeking-help-comparing-addiction-treatment-programs-in-uganda
#4
Julia Vorhölter
Based on ethnographic fieldwork, this article looks at changing discourses and practices in the field of mental health care in Uganda. In particular, it analyzes two psychotherapeutic institutions designed to treat drug- and alcohol-addiction, and their accessibility and affordability for people from different class backgrounds. The first center is a high-class residential facility near Kampala which offers state-of-the-art addiction therapy, but is affordable only for the rich. The second center, a church-funded organization in Northern Uganda, cares mainly for people from poor, rural families who cannot afford exp/tensive treatment...
May 22, 2017: Culture, Medicine and Psychiatry
https://www.readbyqxmd.com/read/28534263/n-acetylaspartylglutamate-inhibits-heroin-self-administration-and-heroin-seeking-behaviors-induced-by-cue-or-priming-in-rats
#5
Huaqiang Zhu, Miaojun Lai, Weisheng Chen, Disen Mei, Fuqiang Zhang, Huifeng Liu, Wenhua Zhou
Activation of presynaptic group II metabotropic glutamate receptors (mGluR2/3) inhibits drug reward and drug-seeking behavior, but the role of N-acetylaspartylglutamate (NAAG), an agonist of endogenous mGluR2/3, in heroin reward and heroin-seeking behavior remained unclear. Here, we aimed to explore the effects of exogenous NAAG on heroin self-administration and heroin-seeking behavior. First, rats were trained to self-administer heroin under a fixed ratio 1 (FR1) schedule for 10 days, then received NAAG (50 or 100 μg/10 μL in each nostril) in the absence or presence of LY341495 (1 mg/kg, i...
May 22, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28531770/treatment-consumption-and-treatment-re-enrollment-in-ghb-dependent-patients-in-the-netherlands
#6
Martijn S van Noorden, Ton Mol, Jeroen Wisselink, Wil Kuijpers, Boukje A G Dijkstra
BACKGROUND: The objective of this study was to assess treatment consumption and re-enrollment in treatment in patients with gamma-hydroxybutyrate (GHB)-dependence in Dutch Addiction Treatment Centers (ATCs) in comparison with other addictions. METHODS: A cohort-study using nationwide administrative data from regular Dutch ATCs associated with the Dutch National Alcohol and Drugs Information System (LADIS), covering an estimated 95% of ATCs. We selected in- and out-patients with alcohol, drug and/or behavioral addictions with a first treatment episode in 2008-2011 and consecutive treatments until 2013 (n=71,679)...
May 16, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28531265/utility-of-nonhuman-primates-in-substance-use-disorders-research
#7
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/28527717/inhibition-of-the-lateral-habenular-camk%C3%A2-abolishes-naloxone-precipitated-conditioned-place-aversion-in-morphine-dependent-mice
#8
Jing Wang, Min Li, Ping Wang, Yunhong Zha, Zhi He, Zicheng Li
Addictive substances mediate positive and negative states promoting compulsive drug use. However, substrates for aversive effects of drugs are not fully understood. We found that inactivation of the lateral habenula (LHb) by microinjection of tetrodotoxin (TTX) abolished naloxone-precipitated conditioned place aversion (CPA) in morphine-dependent mice. We also found that lateral habenular administration of KN-62, a specific inhibitor for calcium/calmodulin dependent protein kinase II (CaMKII), abolished naloxone-precipitated CPA in morphine-dependent mice...
May 17, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28526932/inpatient-addiction-consultation-for-hospitalized-patients-increases-post-discharge-abstinence-and-reduces-addiction-severity
#9
Sarah E Wakeman, Joshua P Metlay, Yuchiao Chang, Grace E Herman, Nancy A Rigotti
BACKGROUND: Alcohol and drug use results in substantial morbidity, mortality, and cost. Individuals with alcohol and drug use disorders are overrepresented in general medical settings. Hospital-based interventions offer an opportunity to engage with a vulnerable population that may not otherwise seek treatment. OBJECTIVE: To determine whether inpatient addiction consultation improves substance use outcomes 1 month after discharge. DESIGN: Prospective quasi-experimental evaluation comparing 30-day post-discharge outcomes between participants who were and were not seen by an addiction consult team during hospitalization at an urban academic hospital...
May 19, 2017: Journal of General Internal Medicine
https://www.readbyqxmd.com/read/28525781/sleep-waves-and-recovery-from-drug-and-alcohol-dependence-towards-a-rhythm-analysis-of-sleep-in-residential-treatment
#10
Robert Meadows, Sarah Nettleton, Joanne Neale
This paper reports on a study of sleep amongst men and women who are living in residential rehabilitation centres in the UK and who are receiving support for their recovery from addiction to alcohol and other forms of substance use. Conceptually and methodologically, the paper draws on the work of the French sociologist Lefebvre and, in particular, his rhythmanalysis. We argue that this approach offers a useful way of exploring sleep in terms of biological, experiential, temporal, spatial and social rhythms...
May 6, 2017: Social Science & Medicine
https://www.readbyqxmd.com/read/28525376/exploiting-ros-and-metabolic-differences-to-kill-cisplatin-resistant-lung-cancer
#11
Medhi Wangpaichitr, Chunjing Wu, Ying Ying Li, Dan J M Nguyen, Hande Kandemir, Sumedh Shah, Shumei Chen, Lynn G Feun, Jeffrey S Prince, Macus T Kuo, Niramol Savaraj
Cisplatin resistance remains a major problem in the treatment of lung cancer. We have discovered that cisplatin resistant (CR) lung cancer cells, regardless of the signaling pathway status, share the common parameter which is an increase in reactive oxygen species (ROS) and undergo metabolic reprogramming. CR cells were no longer addicted to the glycolytic pathway, but rather relied on oxidative metabolism. They took up twice as much glutamine and were highly sensitive to glutamine deprivation. Glutamine is hydrolyzed to glutamate for glutathione synthesis, an essential factor to abrogate high ROS via xCT antiporter...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28523735/variability-in-prescription-opioid-intake-and-reinforcement-amongst-129-substrains
#12
Susan M Jimenez, Aiden F Healy, Michal A Coelho, Chelsea N Brown, Tod E Kippin, Karen K Szumlinski
Opioid abuse in the United States has reached epidemic proportions, with treatment admissions and deaths associated with prescription opioid abuse quadrupling over the past 10 years. Although genetics are theorized to contribute substantially to inter-individual variability in the development, severity, and treatment outcomes of opioid abuse/addiction, little direct preclinical study has focused on the behavioral genetics of prescription opioid reinforcement and drug-taking. Herein, we employed different 129 substrains of mice currently available from The Jackson Laboratory (129S1/SvlmJ, 129X1/SvJ, 129S4/SvJaeJ and 129P3/J) as a model system of genetic variation and assayed mice for oral opioid intake and reinforcement, as well as behavioral and somatic signs of dependence...
May 19, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28523544/drug-addiction-and-histone-code-alterations
#13
Hee-Dae Kim, Tanessa Call, Samantha Magazu, Deveroux Ferguson
Acute and prolonged exposure to drugs of abuse induces changes in gene expression, synaptic function, and neural plasticity in brain regions involved in reward. Numerous genes are involved in this process, and persistent changes in gene expression coincide with epigenetic histone modifications and DNA methylation. Histone modifications are attractive regulatory mechanisms, which can encode complex environmental signals in the genome of postmitotic cells, like neurons. Recently, it has been demonstrated that specific histone modifications are involved in addiction-related gene regulatory mechanisms, by a diverse set of histone-modifying enzymes and readers...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28523543/drug-addiction-and-dna-modifications
#14
Amber N Brown, Jian Feng
Drug addiction is a complex disorder which can be influenced by both genetic and environmental factors. Research has shown that epigenetic modifications can translate environmental signals into changes in gene expression, suggesting that epigenetic changes may underlie the causes and possibly treatment of substance use disorders. This chapter will focus on epigenetic modifications to DNA, which include DNA methylation and several recently defined additional DNA epigenetic changes. We will discuss the functions of DNA modifications and methods for detecting them, followed by a description of the research investigating the function and consequences of drug-induced changes in DNA methylation patterns...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28523287/modeling-risky-decision-making-in-nonhuman-animals-shared-core-features
#15
Sarah R Heilbronner
Understanding the neural mechanisms of risky decision-making is critical to developing appropriate treatments for psychiatric disorders, problem gambling, and addiction to drugs of abuse. Probing neurobiological mechanisms requires the use of nonhuman animal models (particularly rhesus macaques, rats, and mice). However, there is considerable variation across species in risk preferences. Nevertheless, there are shared core features of risky decision-making present across species. As demonstrated with a wide variety of behavioral paradigms, modulators of risk preference observed in humans are readily replicated in model species...
August 2017: Current Opinion in Behavioral Sciences
https://www.readbyqxmd.com/read/28523248/the-keap1-nrf2-system-in-cancer
#16
REVIEW
Keiko Taguchi, Masayuki Yamamoto
Cancer cells first adapt to the microenvironment and then propagate. Mutations in tumor suppressor genes or oncogenes are frequently found in cancer cells. Comprehensive genomic analyses have identified somatic mutations and other alterations in the KEAP1 or NRF2 genes and in well-known tumor suppressor genes or oncogenes, such as TP53, CDKN2A, PTEN, and PIK3CA, in various types of cancer. Aberrant NRF2 activation in cancer cells occurs through somatic mutations in the KEAP1 or NRF2 gene as well as through other mechanisms that disrupt the binding of KEAP1 to NRF2...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28521333/drugging-the-cancers-addicted-to-dna-repair
#17
Jac A Nickoloff, Dennie Jones, Suk-Hee Lee, Elizabeth A Williamson, Robert Hromas
Defects in DNA repair can result in oncogenic genomic instability. Cancers occurring from DNA repair defects were once thought to be limited to rare inherited mutations (such as BRCA1 or 2). It now appears that a clinically significant fraction of cancers have acquired DNA repair defects. DNA repair pathways operate in related networks, and cancers arising from loss of one DNA repair component typically become addicted to other repair pathways to survive and proliferate. Drug inhibition of the rescue repair pathway prevents the repair-deficient cancer cell from replicating, causing apoptosis (termed synthetic lethality)...
November 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28516124/bioinformatic-analysis-for-profiling-drug-induced-chromatin-modification-landscapes-in-mouse-brain-using-chlp-seq-data
#18
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/28513227/temporal-relationship-of-sex-risk-behaviors-and-substance-use-severity-among-men-in-substance-use-treatment
#19
Howard Newville, James L Sorensen, Mary Hatch-Maillette, Donald A Calsyn
Sex risk behaviors and substance use are intertwined. Many men continue to engage in high-risk sexual behaviors even when enrolled in substance use disorder (SUD) treatment. We hypothesized that changes in sex risk behaviors would coincide with changes in drug/alcohol use severity among men in SUD treatment. During an HIV risk-reduction trial, men in methadone maintenance and outpatient drug-free treatment (N = 359) completed assessments at baseline and six months after. We assessed changes in sex risk and substance use severity, using the Addiction Severity Index-Lite (ASI-Lite), controlling for treatment condition...
May 17, 2017: Journal of Sex Research
https://www.readbyqxmd.com/read/28512684/therapeutic-applications-of-classic-hallucinogens
#20
Michael P Bogenschutz, Stephen Ross
This chapter reviews what is known about the therapeutic uses of the serotonergic or classic hallucinogens, i.e., psychoactive drugs such as LSD and psilocybin that exert their effects primarily through agonist activity at serotonin 2A (5HT2A) receptors. Following a review of the history of human use and scientific study of these drugs, the data from clinical research are summarized, including extensive work on the use of classic hallucinogens in the treatment of alcoholism and other addictions, studies of the use of LSD and psilocybin to relieve distress concerning death, particularly in patients with advanced or terminal cancer, and more limited data concerning the use of classic hallucinogens to treat mood and anxiety disorders...
May 18, 2017: Current Topics in Behavioral Neurosciences
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