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Novel Addiction Treatment

Linde Boekhoudt, Elisa S Voets, Jacques P Flores-Dourojeanni, Mieneke Cm Luijendijk, Louk Jmj Vanderschuren, Roger Ah Adan
Attentional impairments and exaggerated impulsivity are key features of psychiatric disorders, such as attention-deficit/hyperactivity disorder, schizophrenia, and addiction. These deficits in attentional performance and impulsive behaviours have been associated with aberrant dopamine (DA) signalling, but it remains unknown whether these deficits result from enhanced DA neuronal activity in the midbrain. Here, we took a novel approach by testing the impact of chemogenetically activating DA neurons in the ventral tegmental area (VTA) or substantia nigra pars compacta (SNc) on attention and impulsivity in the five-choice serial reaction time task (5-CSRTT) in rats...
October 17, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Lorra Garey, Charles Jardin, Brooke Y Kauffman, Carla Sharp, Clayton Neighbors, Norman B Schmidt, Michael J Zvolensky
The Barriers to Cessation Scale (BCS; Macnee & Talsma, 1995a) was developed to assess global and specific perceived barriers that may interfere with the quit process. Although the BCS is widely used in the literature, little scientific work has been devoted to examining the psychometric properties of the measure. Thus, the present study sought to address this gap by evaluating the BCS in a sample of 497 treatment-seeking smokers. The current study examined the factor structure of the BCS, measurement invariance of the BCS subscales across sex and over 2 time points, and evaluated construct validity...
August 15, 2016: Psychological Assessment
S Cuesta, J Batuecas, M J Severin, A Funes, S B Rosso, A M Pacchioni
Cocaine addiction is a chronic relapsing disorder characterized by the loss of control over drug-seeking and taking, and continued drug use regardless of adverse consequences. Despite years of research, effective treatments for psychostimulant addiction have not been identified. Persistent vulnerability to relapse arises from a number of long lasting adaptations in the reward circuitry that mediate the enduring response to the drug. Recently, we reported that the activity of the canonical or Wnt/β-catenin pathway in the Prefrontal Cortex (PFC) is very important in the early stages of cocaine-induced neuroadaptations...
October 8, 2016: Journal of Neurochemistry
Travis T Wager, Thomas A Chappie, David Horton, Ramalakshmi Y Chandrasekaran, Brian M Samas, Elizabeth Dunn-Sims, Cathleen Hsu, Nawshaba Nawreen, Michelle A Vanase-Frawley, Rebecca E O'Connor, Christopher Schmidt, Keith Dlugolenski, Nancy C Stratman, Mark J Majchrzak, Bethany L Kormos, David Nguyen, Aarti Sawant-Basak, Andy N Mead
Dopamine receptor antagonism is a compelling molecular target for the treatment of a range of psychiatric disorders, including substance use disorders. From our corporate compound file we identified a structurally unique D3 receptor (D3R) antagonist scaffold, 1. Through a hybrid approach, we merged key pharmacophore elements from 1 and D3 agonist 2 to yield the novel D3R/D2R antagonist PF-4363467 (3). Compound 3 was designed to possess CNS drug-like properties as defined by its CNS MPO desirability score (≥4/6)...
October 7, 2016: ACS Chemical Neuroscience
Paul J Cocker, M Tremblay, S Kaur, Catharine A Winstanley
RATIONALE: Whilst dopamine agonist therapies can successfully manage the symptoms of diseases such as Parkinson's disease (PD), fibromyalgia and restless leg syndrome, they can also cause impulse control and addiction disorders such as gambling disorder (GD). These compulsive behaviours seriously undermine the utility of such treatments. OBJECTIVES: The objective of the study was to model this phenomenon using a rodent slot machine task (rSMT) in order to investigate the neurobiological basis underlying such behavioural changes...
October 6, 2016: Psychopharmacology
Antonio Ferragud, Adam D Howell, Catherine F Moore, Tina L Ta, Marius C Hoener, Valentina Sabino, Pietro Cottone
Compulsive, binge eating of highly palatable food constitutes a core feature of some forms of obesity and eating disorders, as well as of the recently proposed disorder of food addiction. Trace Amine-Associated Receptor 1 (TAAR1) is a highly conserved G-protein-coupled receptor bound by endogenous trace amines. TAAR1 agonists have been shown to reduce multiple behavioral effects of drugs of abuse through their actions on the mesocorticolimbic system. In this study, we hypothesized that TAAR1 may play a role in compulsive, binge-like eating; we tested this hypothesis by assessing the effects of a TAAR1 agonist, RO5256390, in multiple excessive feeding-related behaviors induced by limiting access to a highly palatable diet in rats...
October 6, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Ayesha Sajid, Aaron Whiteman, Richard L Bell, Marion S Greene, Eric A Engleman, R Andrew Chambers
BACKGROUND AND OBJECTIVES: Fourfold increases in opioid prescribing and dispensations over 2 decades in the U.S. has paralleled increases in opioid addictions and overdoses, requiring new preventative, diagnostic, and treatment strategies. This study examines Prescription Drug Monitoring Program (PDMP) tracking as a novel measure of opioid addiction treatment outcomes in a university-affiliated integrated mental health-addiction treatment clinic. METHODS: Repeated measure parametrics examined PDMP and urine drug screening (UDS) data before and after first injection for all patients (N = 68) who received at least one long-acting naltrexone injection (380 mg/IM) according to diagnostic groupings of having either (i) alcohol (control); (ii) opioid; or (iii) combined alcohol and opioid use disorders...
October 2016: American Journal on Addictions
Kalyan N Rao, Alena M Sentir, Eric A Engleman, Richard L Bell, Leslie A Hulvershorn, Alan Breier, R Andrew Chambers
RATIONAL: Prefrontal cortical (PFC)-hippocampal-striatal circuits, interconnected via glutamatergic signaling, are dysfunctional in mental illnesses that involve addiction vulnerability. OBJECTIVES: In healthy and neurodevelopmentally altered rats, we examined how Radial Arm Maze (RAM) performance estimates addiction vulnerability, and how starting a glutamatergic modulating agent, N-acetyl cysteine (NAC) in adolescence alters adult mental illness and/or addiction phenotypes...
September 17, 2016: Psychopharmacology
Terence G Hall, Yi Yu, Sudharshan Eathiraj, Yunxia Wang, Ronald E Savage, Jean-Marc Lapierre, Brian Schwartz, Giovanni Abbadessa
Dysregulation of Fibroblast Growth Factor Receptor (FGFR) signaling through amplifications, mutations, and gene fusions has been implicated in a broad array of cancers (e.g. liver, gastric, ovarian, endometrial, and bladder). ARQ 087 is a novel, ATP competitive, small molecule, multi-kinase inhibitor with potent in vitro and in vivo activity against FGFR addicted cell lines and tumors. Biochemically, ARQ 087 exhibited IC50 values of 1.8 nM for FGFR2, and 4.5 nM for FGFR1 and 3. In cells, inhibition of FGFR2 auto-phosphorylation and other proteins downstream in the FGFR pathway (FRS2α, AKT, ERK) was evident by the response to ARQ 087 treatment...
2016: PloS One
Nya L Fraleigh, Justin Boudreau, Nitin Bhardwaj, Nelson F Eng, Yanal Murad, Robert Lafrenie, Reinaldo Acevedo, Reynaldo Oliva, Francisco Diaz-Mitoma, Hoang-Thanh Le
Tobacco smoking is recognized as a global pandemic resulting in 6 million deaths per year. Despite a variety of anti-smoking products available to aid with tobacco cessation, the majority of people who attempt to quit smoking relapse within 6 months due to the addictive nature of nicotine. An immunotherapy approach could offer a promising treatment option by inducing a potent selective antibody response against nicotine in order to block its distribution to the brain and its addictive effects in the central nervous system...
August 2016: Heliyon
Gabriele Di Giammarco, Daniele Marinelli, Massimiliano Foschi, Michele Di Mauro
Tricuspid valve (TV) endocarditis is a common complication in intravenous drug addicts. In case of TV replacement, the main issue is the high risk of new endocarditis on TV prosthesis. On November 2014, a 44 year-old male patient with a history of intravenous drug addiction was referred for TV endocarditis owing to Staphylococcus aureus and severe regurgitation complicated by pulmonary embolism and heart failure. Preoperative echocardiography showed a large vegetation of the anterior leaflet (1.95 × 0.92 cm) covering a huge hole in the leaflet itself...
July 2016: Innovations: Technology and Techniques in Cardiothoracic and Vascular Surgery
Bruce Steinberg, Kenneth Blum, Thomas McLaughlin, Joel Lubar, Marcelo Febo, Eric R Braverman, Rajendra D Badgaiyan
Attention Deficit-Hyperactivity Disorder (ADHD) often continues into adulthood. Recent neuroimaging studies found lowered baseline dopamine tone in the brains of affected individuals that may place them at risk for Substance Use Disorder (SUD). This is an observational case study of the potential for novel management of Adult ADHD with a non-addictive glutaminergic-dopaminergic optimization complex KB200z. Low-resolution electromagnetic tomography (LORETA) was used to evaluate the effects of KB220z on a 72-year-old male with ADHD, at baseline and one hour following administration...
2016: Open Journal of Clinical & Medical Case Reports
Elizabeth J Santa Ana, Steven D LaRowe, Kent Armeson, Kayla E Lamb, Karen Hartwell
BACKGROUND: Prior studies have shown that Group Motivational Interviewing (GMI) for dually diagnosed patients holds promise for increasing treatment engagement. OBJECTIVES: The current study evaluated the impact of a novel GMI protocol that included tobacco-specific components (referred to as "Tobacco GMI or T-GMI") targeting enhanced engagement in smoking cessation treatment. METHODS: Thirty-seven primary alcohol and nicotine-dependent cigarette smoking homeless Veterans with co-morbid psychiatric conditions were recruited to receive four GMI sessions over 4 consecutive days...
October 2016: American Journal on Addictions
Yu-Ching Hsu, Yu-Chiao Chiu, Yidong Chen, Tzu-Hung Hsiao, Eric Y Chuang
BACKGROUND: The advance in targeted therapy has greatly increased the effectiveness of clinical cancer therapy and reduced the cytotoxicity of treatments to normal cells. However, patients still suffer from cancer relapse due to the occurrence of drug resistance. It is of great need to explore potential combinatorial drug therapy since individual drug alone may not be sufficient to inhibit continuous activation of cancer-addicted genes or pathways. The DREAM challenge has confirmed the potentiality of computational methods for predicting synergistic drug combinations, while the prediction accuracy can be further improved...
2016: BMC Systems Biology
Yun Hu, Daniel Smith, Evan Frazier, Reece Hoerle, Marion Ehrich, Chenming Zhang
Owing to the urgent need for more effective treatment against nicotine addiction, a hybrid nanoparticle-based nicotine vaccine (NanoNiccine) was developed in this study. NanoNiccine was composed of a poly(lactide-co-glycolide) acid (PLGA) core, keyhole limpet hemocyanin (KLH) as an adjuvant protein enclosed within the PLGA core, a lipid layer, and nicotine haptens conjugated to the outer surface of the lipid layer. In contrast to the traditional nicotine vaccine, NanoNiccine is not a nicotine-protein conjugate vaccine...
November 2016: Biomaterials
Xin Zhang, Deyong Jia, Junping Ao, Huijuan Liu, Yi Zang, Mohammad Azam, Samy Habib, Jia Li, Xinsen Ruan, Hao Jia, Xueying Wang, Baojie Li
Chronic myeloid leukemia (CML) treatment with BCR-ABL inhibitors is often hampered by development of drug resistance. In a screen for novel chemotherapeutic drug candidates with genotoxic activity, we identified a bisindolylmaleimide derivative, IX, as a small molecule compound with therapeutic potential against CML including drug-resistant CML. We show that Bisindolylmaleimide IX inhibits DNA topoisomerase, generates DNA breaks, activates the Atm-p53 and Atm-Chk2 pathways, and induces cell cycle arrest and cell death...
August 24, 2016: Oncotarget
Zheng-Xiong Xi, Rui Song, Xia Li, Guan-Yi Lu, Xiao-Qing Peng, Yi He, Guo-Hua Bi, Peter Shen, Hong-Ju Yang, Haiying Zhang, Jin Li, Mark Froimowitz, Eliot L Gardner
Agonist replacement therapies have been successfully used for treatment of opiate and nicotine addiction, but not for cocaine addiction. One of the major obstacles is the cocaine-like addictive potential of the agonists themselves. We report here an atypical dopamine (DA) transporter (DAT) inhibitor, CTDP-32 476, that may have translational potential for treating cocaine addiction. In vitro ligand binding assays suggest that CTDP-32 476 is a potent and selective DAT inhibitor and a competitive inhibitor of cocaine binding to the DAT...
August 18, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Mihaela D Iordanova, Mickael L D Deroche, Guillem R Esber, Geoffrey Schoenbaum
Extinction is a fundamental form of memory updating in which one learns to stop expecting an event that no longer occurs. This learning ensues when one experiences a change in environmental contingencies, that is, when an expected outcome fails to occur (simple extinction), or when a novel inflated expectation of a double outcome (overexpectation) is in conflict with the real outcome, and is a process that has been linked to amygdala function. Here, we show that in rats, the same neuronal population in the amygdala central nucleus updates reward expectancies and behaviour in both types of extinction, and neural changes in one paradigm are reflected in the other...
2016: Nature Communications
Deborah J Luessen, Tyler P Hinshaw, Haiguo Sun, Allyn C Howlett, Glen Marrs, Brian A McCool, Rong Chen
Dysregulated expression and function of dopamine D2 receptors (D2Rs) are implicated in drug addiction, Parkinson's disease and schizophrenia. In the current study, we examined whether D2Rs are modulated by regulator of G protein signaling 2 (RGS2), a member of the RGS family that regulates G protein signaling via acceleration of GTPase activity. Using neuroblastoma 2a (N2A) cells, we found that RGS2 was immunoprecipitated by aluminum fluoride-activated Gαi2 proteins. RGS2 siRNA knockdown enhanced membrane [(35)S] GTPγS binding to activated Gαi/o proteins, augmented inhibition of cAMP accumulation and increased ERK phosphorylation in the presence of a D2/D3R agonist quinpirole when compared to scrambled siRNA treatment...
November 2016: Neuropharmacology
Diane M Damez-Werno, HaoSheng Sun, Kimberly N Scobie, Ningyi Shao, Jaclyn Rabkin, Caroline Dias, Erin S Calipari, Ian Maze, Catherine J Pena, Deena M Walker, Michael E Cahill, Ramesh Chandra, Amy Gancarz, Ezekiell Mouzon, Joseph A Landry, Hannah Cates, Mary-Kay Lobo, David Dietz, C David Allis, Ernesto Guccione, Gustavo Turecki, Paola Defilippi, Rachael L Neve, Yasmin L Hurd, Li Shen, Eric J Nestler
Repeated cocaine exposure regulates transcriptional regulation within the nucleus accumbens (NAc), and epigenetic mechanisms-such as histone acetylation and methylation on Lys residues-have been linked to these lasting actions of cocaine. In contrast to Lys methylation, the role of histone Arg (R) methylation remains underexplored in addiction models. Here we show that protein-R-methyltransferase-6 (PRMT6) and its associated histone mark, asymmetric dimethylation of R2 on histone H3 (H3R2me2a), are decreased in the NAc of mice and rats after repeated cocaine exposure, including self-administration, and in the NAc of cocaine-addicted humans...
August 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
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