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https://www.readbyqxmd.com/read/28229895/impulse-control-disorders-and-levodopa-induced-dyskinesias-in-parkinson-s-disease-an-update
#1
REVIEW
Valerie Voon, T Celeste Napier, Michael J Frank, Veronique Sgambato-Faure, Anthony A Grace, Maria Rodriguez-Oroz, Jose Obeso, Erwan Bezard, Pierre-Olivier Fernagut
Dopaminergic medications used in the treatment of patients with Parkinson's disease are associated with motor and non-motor behavioural side-effects, such as dyskinesias and impulse control disorders also known as behavioural addictions. Levodopa-induced dyskinesias occur in up to 80% of patients with Parkinson's after a few years of chronic treatment. Impulse control disorders, including gambling disorder, binge eating disorder, compulsive sexual behaviour, and compulsive shopping occur in about 17% of patients with Parkinson's disease on dopamine agonists...
March 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28221362/disrupted-iron-regulation-in-the-brain-and-periphery-in-cocaine-addiction
#2
K D Ersche, J Acosta-Cabronero, P S Jones, H Ziauddeen, R P L van Swelm, C M M Laarakkers, R Raha-Chowdhury, G B Williams
Stimulant drugs acutely increase dopamine neurotransmission in the brain, and chronic use leads to neuroadaptive changes in the mesolimbic dopamine system and morphological changes in basal ganglia structures. Little is known about the mechanisms underlying these changes but preclinical evidence suggests that iron, a coenzyme in dopamine synthesis and storage, may be a candidate mediator. Iron is present in high concentrations in the basal ganglia and stimulant drugs may interfere with iron homeostasis. We hypothesised that morphological brain changes in cocaine addiction relate to abnormal iron regulation in the brain and periphery...
February 21, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28202458/sensitivity-to-pi3k-and-akt-inhibitors-is-mediated-by-divergent-molecular-mechanisms-in-subtypes-of-dlbcl
#3
Tabea Erdmann, Pavel Klener, James T Lynch, Michael Grau, Petra Vočková, Jan Molinsky, Diana Tuskova, Kevin Hudson, Urszula M Polanska, Michael Grondine, Michele Mayo, Beiying Dai, Matthias Pfeifer, Kristian Erdmann, Daniela Schwammbach, Myroslav Zapukhlyak, Annette M Staiger, German Ott, Wolfgang E Berdel, Barry R Davies, Francisco Cruzalegui, Marek Trneny, Peter Lenz, Simon T Barry, Georg Lenz
Activated B-cell-like (ABC) and germinal center B-cell-like (GCB) diffuse large B-cell lymphoma (DLBCL) represent the two major molecular DLBCL subtypes. They are characterized by differences in clinical course and by divergent addiction to oncogenic pathways. To determine activity of novel compounds in these two subtypes, we conducted an unbiased pharmacologic in vitro screen. The phosphatidylinositol-3-kinase (PI3K) alpha/delta (PI3Kα/δ) inhibitor AZD8835 showed marked potency in ABC DLBCL models, whereas the protein kinase B (AKT) inhibitor AZD5363 induced apoptosis in PTEN-deficient DLBCLs irrespective of their molecular subtype...
February 15, 2017: Blood
https://www.readbyqxmd.com/read/28199070/randomized-controlled-trial-comparing-exercise-to-health-education-for-stimulant-use-disorder-results-from-the-ctn-0037-stimulant-reduction-intervention-using-dosed-exercise-stride-study
#4
Madhukar H Trivedi, Tracy L Greer, Chad D Rethorst, Thomas Carmody, Bruce D Grannemann, Robrina Walker, Diane Warden, Kathy Shores-Wilson, Mark Stoutenberg, Neal Oden, Meredith Silverstein, Candace Hodgkins, Lee Love, Cindy Seamans, Angela Stotts, Trey Causey, Regina P Szucs-Reed, Paul Rinaldi, Hugh Myrick, Michele Straus, David Liu, Robert Lindblad, Timothy Church, Steven N Blair, Edward V Nunes
OBJECTIVE: To evaluate exercise as a treatment for stimulant use disorders. METHODS: The STimulant Reduction Intervention using Dosed Exercise (STRIDE) study was a randomized clinical trial conducted in 9 residential addiction treatment programs across the United States from July 2010 to February 2013. Of 497 adults referred to the study, 302 met all eligibility criteria, including DSM-IV criteria for stimulant abuse and/or dependence, and were randomized to either a dosed exercise intervention (Exercise) or a health education intervention (Health Education) control, both augmenting treatment as usual and conducted thrice weekly for 12 weeks...
February 14, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28194001/enhancing-vta-cav1-3-l-type-ca-2-channel-activity-promotes-cocaine-and-mood-related-behaviors-via-overlapping-ampa-receptor-mechanisms-in-the-nucleus-accumbens
#5
A Martínez-Rivera, J Hao, T F Tropea, T P Giordano, M Kosovsky, R C Rice, A Lee, R L Huganir, J Striessnig, N A Addy, S Han, A M Rajadhyaksha
Genetic factors significantly influence susceptibility for substance abuse and mood disorders. Rodent studies have begun to elucidate a role of Cav1.3 L-type Ca(2+) channels in neuropsychiatric-related behaviors, such as addictive and depressive-like behaviors. Human studies have also linked the CACNA1D gene, which codes for the Cav1.3 protein, with bipolar disorder. However, the neurocircuitry and the molecular mechanisms underlying the role of Cav1.3 in neuropsychiatric phenotypes are not well established...
February 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28174112/epigenetic-basis-of-the-dark-side-of-alcohol-addiction
#6
REVIEW
Subhash C Pandey, Evan Kyzar, Huaibo Zhang
Alcoholism is a complex brain disease characterized by three distinct stages of the addiction cycle that manifest as neuroadaptive changes in the brain. One such stage of the addiction cycle is alcohol withdrawal and the negative affective states that promote drinking and maintain addiction. Repeated alcohol use, genetic predisposition to alcoholism and anxiety, and alcohol exposure during crucial developmental periods all contribute to the development of alcohol-induced withdrawal and negative affective symptoms...
February 4, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28146243/effect-of-a-brief-memory-updating-intervention-on-smoking-behavior-a-randomized-clinical-trial
#7
Lisa J Germeroth, Matthew J Carpenter, Nathaniel L Baker, Brett Froeliger, Steven D LaRowe, Michael E Saladin
Importance: Recent research on addiction-related memory processes suggests that protracted extinction training following brief cue-elicited memory retrieval (ie, retrieval-extinction [R-E] training) can attenuate/eradicate the ability of cues to elicit learned behaviors. One study reported that cue-elicited craving among detoxified heroin addicts was substantially attenuated following R-E training and through 6-month follow-up. Objective: To build on these impressive findings by examining whether R-E training could attenuate smoking-related craving and behavior...
February 1, 2017: JAMA Psychiatry
https://www.readbyqxmd.com/read/28123023/role-of-taar1-within-the-subregions-of-the-mesocorticolimbic-dopaminergic-system-in-cocaine-seeking-behavior
#8
Jian-Feng Liu, Justin N Siemian, Robert Seaman, Yanan Zhang, Jun-Xu Li
: A novel G-protein coupled receptor, trace amine-associated receptor 1 (TAAR1), has been shown to be a promising target to prevent stimulant relapse. Our recent studies showed that systemic administration of TAAR1 agonists decreased abuse-related behaviors of cocaine. However, the role of TAAR1 in specific subregions of the reward system in drug addiction is unknown. Here, using a local pharmacological activation method, we assessed the role of TAAR1 within the subregions of the mesocorticolimbic system: that is, the VTA, the prelimbic cortex (PrL), and infralimbic cortex of medial prefrontal cortex, the core and shell of NAc, BLA, and CeA, on cue- and drug-induced cocaine-seeking in the rat cocaine reinstatement model...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28115739/genome-wide-association-study-of-therapeutic-opioid-dosing-identifies-a-novel-locus-upstream-of-oprm1
#9
A H Smith, K P Jensen, J Li, Y Nunez, L A Farrer, H Hakonarson, S D Cook-Sather, H R Kranzler, J Gelernter
Opioids are very effective analgesics, but they are also highly addictive. Methadone is used to treat opioid dependence (OD), acting as a selective agonist at the μ-opioid receptor encoded by the gene OPRM1. Determining the optimal methadone maintenance dose is time consuming; currently, no biomarkers are available to guide treatment. In methadone-treated OD subjects drawn from a case and control sample, we conducted a genome-wide association study of usual daily methadone dose. In African-American (AA) OD subjects (n=383), we identified a genome-wide significant association between therapeutic methadone dose (mean=68...
March 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28111764/emerging-role-of-epigenetic-mechanisms-in-alcohol-addiction
#10
Tiffani D M Berkel, Subhash C Pandey
Alcohol use disorder (AUD) is a complex disorder with an array of persistent behavioral and neurochemical manifestations. Both genetic and environmental factors are known to contribute to the development of AUD, and recent studies on alcohol exposure and subsequent changes in gene expression suggest the importance of epigenetic mechanisms. In particular, histone modifications and DNA methylation have emerged as important regulators of gene expression and associated phenotypes of AUD. Given the therapeutic potential of epigenetic targets, this review aims to summarize the role of epigenetic regulation in our current understanding of AUD by evaluating known epigenetic signatures of brain regions critical to addictive behaviors in both animal and human studies throughout various stages of AUD...
January 23, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28104295/systematic-drug-sensitivity-testing-reveals-synergistic-growth-inhibition-by-dasatinib-or-mtor-inhibitors-with-paclitaxel-in-ovarian-granulosa-cell-tumor-cells
#11
Ulla-Maija Haltia, Noora Andersson, Bhagwan Yadav, Anniina Färkkilä, Evgeny Kulesskiy, Matti Kankainen, Jing Tang, Ralf Bützow, Annika Riska, Arto Leminen, Markku Heikinheimo, Olli Kallioniemi, Leila Unkila-Kallio, Krister Wennerberg, Tero Aittokallio, Mikko Anttonen
OBJECTIVE: Resistance to standard chemotherapy poses a major clinical problem in the treatment of ovarian cancer patients. Adult-type granulosa cell tumor (AGCT) is a unique ovarian cancer subtype for which efficient treatment options are lacking in advanced disease. To this end, systematic drug response and transcriptomics profiling were performed to uncover new therapy options for AGCTs. METHODS: The responses of three primary and four recurrent AGCTs to 230 anticancer compounds were screened in vitro using a systematic drug sensitivity and resistance testing (DSRT) platform, coupled with mRNA sequencing...
January 16, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28065792/the-analgesic-effects-of-oxytocin-in-the-peripheral-and-central-nervous-system
#12
Qing Xin, Bo Bai, Wenyan Liu
Pain is a ubiquitously unpleasant feeling among humans as well as many animal species often caused by actual and potential tissue damage. However, it is absolutely crucial for our survival in many ways. Acute pain can signal the presence of danger or life-threatenting events, which help escape noxious stimuli. By contrast, when pain becomes chronic or persistent, it becomes an encumbrance and exerts deleterious effects to the body and mind, often co-occured with anxiety and depression. Additionaly, chronic pain is more or less an economic burden for the patients because it requires immediate medical treatments and seriously hinders pepople in their work...
February 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28062254/the-effects-of-d-govadine-on-conditioned-place-preference-with-d-amphetamine-or-food-reward
#13
Maya O Nesbit, Carine Dias, Anthony G Phillips
Tetrahydroprotoberberines (THPB) have a high affinity for dopamine (DA) D1 and D2 receptors and may provide a novel treatment for drug addiction. We assessed the effects of the THPB d-govadine on the acquisition, expression, extinction and reinstatement of d-amphetamine-(1.5mg/kg, i.p.) induced conditioned place preference (CPP). Furthermore, the effects of d-govadine on conditioned association between contextual stimuli and a natural reward were examined using food-induced CPP. In separate experiments, rats received d-govadine (0, 0...
March 15, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28042872/infralimbic-glun2a-containing-nmda-receptors-modulate-reconsolidation-of-cocaine-self-administration-memory
#14
Madalyn Hafenbreidel, Carolynn Rafa Todd, Devin Mueller
Addiction is characterized by high relapse susceptibility, and relapse can be triggered by drug-associated cues. Cue presentation induces retrieval of the drug-cue memory, which becomes labile and must be reconsolidated into long-term storage. Repeated unpaired cue presentation, however, induces extinction. Cue-reactivity can be reduced by blocking reconsolidation or facilitating extinction, which are mediated by NMDA receptors (NMDArs). However, the role of NMDArs in either process following self-administration is unclear...
January 2, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28039543/sigma-receptors-and-alcohol-use-disorders
#15
Valentina Sabino, Pietro Cottone
Although extensive research has focused on understanding the neurobiological mechanisms underlying alcohol addiction, pharmacological treatments for alcohol use disorders are very limited and not always effective. This constraint has encouraged the search for novel pharmacological targets for alcoholism therapy. Sigma receptors were shown to mediate some of the properties of cocaine and amphetamine, which was attributed to the direct binding of psychostimulants to these receptors. More recently, the role of sigma receptors in the rewarding and reinforcing effects of alcohol was also proposed, and it was suggested that their hyperactivity may result in excessive alcohol drinking...
December 31, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28033474/hypothesizing-that-neuropharmacological-and-neuroimaging-studies-of-glutaminergic-dopaminergic-optimization-complex-kb220z-are-associated-with-dopamine-homeostasis-in-reward-deficiency-syndrome-rds
#16
Kenneth Blum, Marcelo Febo, Lyle Fried, Mona Li, Kristina Dushaj, Eric R Braverman, Thomas McLaughlin, Bruce Steinberg, Rajendra D Badgaiyan
BACKGROUND: There is need for better treatments of addictive behaviors, both substance and non-substance related, termed Reward Deficiency Syndrome (RDS). While the FDA has approved pharmaceuticals under the umbrella term Medication Assisted Treatment (MAT), these drugs are not optimal. OBJECTIVES: It is our contention that these drugs work well in the short-term by blocking dopamine function leading to psychological extinction. However, use of buprenorphine/Naloxone over a long period of time results in unwanted addiction liability, reduced emotional affect, and mood changes including suicidal ideation...
March 21, 2017: Substance Use & Misuse
https://www.readbyqxmd.com/read/28019026/psychedelics-as-medicines-an-emerging-new-paradigm
#17
D E Nichols, M W Johnson, C D Nichols
Scientific interest in serotonergic psychedelics (e.g., psilocybin and LSD; 5-HT2A receptor agonists) has dramatically increased within the last decade. Clinical studies administering psychedelics with psychotherapy have shown preliminary evidence of robust efficacy in treating anxiety and depression, as well as addiction to tobacco and alcohol. Moreover, recent research has suggested that these compounds have potential efficacy against inflammatory diseases through novel mechanisms, with potential advantages over existing antiinflammatory agents...
November 4, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28018836/novel-therapeutics-for-addiction-behavioral-and-neuroeconomic-approaches
#18
Warren K Bickel, Alexandra M Mellis, Sarah E Snider, Lara Moody, Jeffrey S Stein, Amanda J Quisenberry
The maturing fields of behavioral- and neuro-economics provides conceptual understanding of the Competing Neurobehavioral Decision Systems theory (CNDS) and reinforcer pathology (i.e. high valuation of and excessive preference for drug reinforcers) allowing us to coherently categorize treatments into a theoretically comprehensive framework of addiction. In this chapter, we identify and clarify how existing and novel interventions can ameliorate reinforcer pathology in light of the CNDS and be leveraged to treat addiction...
September 2016: Current Treatment Options in Psychiatry
https://www.readbyqxmd.com/read/27993694/effects-of-chronic-methamphetamine-on-psychomotor-and-cognitive-functions-and-dopamine-signaling-in-the-brain
#19
Panayotis K Thanos, Ronald Kim, Foteini Delis, Mark J Rocco, Jacob Cho, Nora D Volkow
Methamphetamine (MA) studies in animals usually involve acute, binge, or short-term exposure to the drug. However, addicts take substantial amounts of MA for extended periods of time. Here we wished to study the effects of MA exposure on brain and behavior, using an animal model analogous to this pattern of MA intake. MA doses, 4 and 8mg/kg/day, were based on previously reported average daily freely available MA self-administration levels. We examined the effects of 16 week MA treatment on psychomotor and cognitive function in the rat using open field and novel object recognition tests and we studied the adaptations of the dopaminergic system, using in vitro and in vivo receptor imaging...
March 1, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/27991902/crystal-structures-of-human-glycine-receptor-%C3%AE-3-bound-to-a-novel-class-of-analgesic-potentiators
#20
Xin Huang, Paul L Shaffer, Shawn Ayube, Howard Bregman, Hao Chen, Sonya G Lehto, Jason A Luther, David J Matson, Stefan I McDonough, Klaus Michelsen, Matthew H Plant, Stephen Schneider, Jeffrey R Simard, Yohannes Teffera, Shuyan Yi, Maosheng Zhang, Erin F DiMauro, Jacinthe Gingras
Current therapies to treat persistent pain and neuropathic pain are limited by poor efficacy, side effects and risk of addiction. Here, we present a novel class of potent selective, central nervous system (CNS)-penetrant potentiators of glycine receptors (GlyRs), ligand-gated ion channels expressed in the CNS. AM-1488 increased the response to exogenous glycine in mouse spinal cord and significantly reversed mechanical allodynia induced by nerve injury in a mouse model of neuropathic pain. We obtained an X-ray crystal structure of human homopentameric GlyRα3 in complex with AM-3607, a potentiator of the same class with increased potency, and the agonist glycine, at 2...
December 19, 2016: Nature Structural & Molecular Biology
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