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https://www.readbyqxmd.com/read/28065792/the-analgesic-effects-of-oxytocin-in-the-peripheral-and-central-nervous-system
#1
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...
January 5, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28062254/the-effects-of-d-govadine-on-conditioned-place-preference-with-d-amphetamine-or-food-reward
#2
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...
January 3, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28042872/infralimbic-glun2a-containing-nmda-receptors-modulate-reconsolidation-of-cocaine-self-administration-memory
#3
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
#4
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
#5
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...
December 29, 2016: Substance Use & Misuse
https://www.readbyqxmd.com/read/28019026/psychedelics-as-medicines-an-emerging-new-paradigm
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/27990326/brain-mechanisms-of-change-in-addictions-treatment-models-methods-and-emerging-findings
#10
Tammy Chung, Antonio Noronha, Kathleen M Carroll, Marc N Potenza, Kent Hutchison, Vince D Calhoun, John D E Gabrieli, Jon Morgenstern, Sara Jo Nixon, Bruce E Wexler, Judson Brewer, Lara Ray, Francesca Filbey, Timothy J Strauman, Hedy Kober, Sarah W Feldstein Ewing
Increased understanding of "how" and "for whom" treatment works at the level of the brain has potential to transform addictions treatment through the development of innovative neuroscience-informed interventions. The 2015 Science of Change meeting bridged the fields of neuroscience and psychotherapy research to identify brain mechanisms of behavior change that are "common" across therapies, and "specific" to distinct behavioral interventions. Conceptual models of brain mechanisms underlying effects of Cognitive Behavioral Therapy, mindfulness interventions, and Motivational Interviewing were discussed...
September 2016: Current Addiction Reports
https://www.readbyqxmd.com/read/27989838/opioid-gene-expression-changes-and-post-translational-histone-modifications-at-promoter-regions-in-the-rat-nucleus-accumbens-after-acute-and-repeated-3-4-methylenedioxy-methamphetamine-mdma-exposure
#11
Francesca Felicia Caputi, Martina Palmisano, Lucia Carboni, Sanzio Candeletti, Patrizia Romualdi
The recreational drug of abuse 3,4-methylenedioxymethamphetamine (MDMA) has been shown to produce neurotoxic damage and long-lasting changes in several brain areas. In addition to the involvement of serotoninergic and dopaminergic systems, little information exists about the contribution of nociceptin/orphaninFQ (N/OFQ)-NOP and dynorphin (DYN)-KOP systems in neuronal adaptations evoked by MDMA. Here we investigated the behavioral and molecular effects induced by acute (8mg/kg) or repeated (8mg/kg twice daily for seven days) MDMA exposure...
October 29, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27980118/role-of-taar1-within-the-subregions-of-the-mesocorticolimbic-dopaminergic-system-in-cocaine-seeking-behavior
#12
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, i...
December 15, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27941799/inhibition-of-notch-pathway-arrests-pten-deficient-advanced-prostate-cancer-by-triggering-p27-driven-cellular-senescence
#13
Ajinkya Revandkar, Maria Luna Perciato, Alberto Toso, Abdullah Alajati, Jingjing Chen, Hermeto Gerber, Mitko Dimitrov, Andrea Rinaldi, Nicolas Delaleu, Emiliano Pasquini, Rocco D'Antuono, Sandra Pinton, Marco Losa, Letizia Gnetti, Alberto Arribas, Patrick Fraering, Francesco Bertoni, Alain Nepveu, Andrea Alimonti
Activation of NOTCH signalling is associated with advanced prostate cancer and treatment resistance in prostate cancer patients. However, the mechanism that drives NOTCH activation in prostate cancer remains still elusive. Moreover, preclinical evidence of the therapeutic efficacy of NOTCH inhibitors in prostate cancer is lacking. Here, we provide evidence that PTEN loss in prostate tumours upregulates the expression of ADAM17, thereby activating NOTCH signalling. Using prostate conditional inactivation of both Pten and Notch1 along with preclinical trials carried out in Pten-null prostate conditional mouse models, we demonstrate that Pten-deficient prostate tumours are addicted to the NOTCH signalling...
December 12, 2016: Nature Communications
https://www.readbyqxmd.com/read/27941351/anti-cancer-effect-of-cap-translation-inhibitor-4egi-1-in-human-glioma-u87-cells-involvement-of-mitochondrial-dysfunction-and-er-stress
#14
Ming Wu, Chi Zhang, Xue-Jun Li, Qing Liu, Siyi Wanggou
BACKGROUND: Cancer cells are frequently addicted to deregulated oncogenic protein translation that usually arises as a consequence of increased signaling flux from eIF4F activation. The small molecule 4EG-I, a potent inhibitor of translation initiation through disrupting eIF4E/eIF4G interaction, has been shown to exert anticancer effects in animal models of human cancers. METHODS: Here, we extensively investigated the anticancer activity of 4EGI-1 in human glioma U87 cells...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27923780/attentional-bias-modification-with-serious-game-elements-evaluating-the-shots-game
#15
Wouter J Boendermaker, Soraya Sanchez Maceiras, Marilisa Boffo, Reinout W Wiers
BACKGROUND: Young adults often experiment with heavy use of alcohol, which poses severe health risks and increases the chance of developing addiction problems. In clinical patients, cognitive retraining of automatic appetitive processes, such as selective attention toward alcohol (known as "cognitive bias modification of attention," or CBM-A), has been shown to be a promising add-on to treatment, helping to prevent relapse. OBJECTIVE: To prevent escalation of regular use into problematic use in youth, motivation appears to play a pivotal role...
December 6, 2016: JMIR Serious Games
https://www.readbyqxmd.com/read/27917870/high-frequency-stimulation-of-the-subthalamic-nucleus-blocks-compulsive-like-re-escalation-of-heroin-taking-in-rats
#16
Carrie L Wade, Marsida Kallupi, Daniel O Hernandez, Emmanuel Breysse, Giordano de Guglielmo, Elena Crawford, George F Koob, Paul Schweitzer, Christelle Baunez, Olivier George
Opioid addiction, including addiction to heroin, has dramatically increased in the last decade. The cost and pervasiveness of heroin addiction, including resistance to recovery from addiction, provide a compelling basis for developing novel therapeutic strategies. Deep brain stimulation may represent a viable alternative strategy for the treatment of intractable heroin addiction particularly in individuals who are resistant to traditional therapies. Here, we provide preclinical evidence of the therapeutic potential of high-frequency stimulation of the subthalamic nucleus (STN HFS) for heroin addiction...
December 5, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27909991/the-role-of-orexins-hypocretins-in-alcohol-use-and-abuse
#17
Leigh C Walker, Andrew J Lawrence
Addiction is a chronic relapsing disorder characterized by compulsive drug seeking and drug taking despite negative consequences. Alcohol abuse and addiction have major social and economic consequences and cause significant morbidity and mortality worldwide. Currently available therapeutics are inadequate, outlining the need for alternative treatments. Detailed knowledge of the neurocircuitry and brain chemistry responsible for aberrant behavior patterns should enable the development of novel pharmacotherapies to treat addiction...
December 2, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27889489/the-drug-candidate-adx71441-is-a-novel-potent-and-selective-positive-allosteric-modulator-of-the-gabab-receptor-with-a-potential-for-treatment-of-anxiety-pain-and-spasticity
#18
Mikhail Kalinichev, Françoise Girard, Hasnaà Haddouk, Mélanie Rouillier, Eric Riguet, Isabelle Royer-Urios, Vincent Mutel, Robert Lütjens, Sonia Poli
Positive allosteric modulation of the GABAB receptor is a promising alternative to direct activation of the receptor as a therapeutic approach for treatment of addiction, chronic pain, anxiety, epilepsy, autism, Fragile X syndrome, and psychosis. Here we describe in vitro and in vivo characterization of a novel, potent and selective GABAB positive allosteric modulator (PAM) N-(5-(4-(4-chloro-3-fluorobenzyl)-6-methoxy-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)-2-fluorophenyl)acetamide (ADX71441). In vitro, Schild plot and reversibility tests at the target confirmed PAM properties of the compound...
March 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27876887/high-energy-particle-radiation-associated-oncogenic-transformation-in-normal-mice-insight-into-the-connection-between-activation-of-oncotargets-and-oncogene-addiction
#19
Natarajan Aravindan, Sheeja Aravindan, Krishnan Manickam, Mohan Natarajan
Concerns on high-energy particle radiation-induced tumorigenic transformation of normal tissue in astronauts, and in cancer patients undergoing radiotherapy, emphasizes the significance of elucidating the mechanisms involved in radiogenic transformation processes. Mostly used genetically modified or tumor-prone models are less reliable in determining human health risk in space or protracted post-treatment normal tissue toxicity. Here, in wild type C57BL/6 mice, we related the deregulation of distinctive set of tissue-specific oncotargets in major organs upon (56)Fe (600 MeV/amu; 0...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27872099/conflicting-signals-for-cancer-treatment
#20
Pierre Sujobert, Alain Trautmann
Next-generation sequencing technologies have provided us with a precise description of the mutational burden of cancers, making it possible to identify targetable oncogene addictions. However, the emergence of resistant clones is an inevitable limitation of therapies targeting these addictions. Alternative approaches to cancer treatment are therefore required. We propose here a novel approach, based on the notion of conflicting signals and on a phenotypic description of cancer cells. "Phenotype" is an inherently complex notion that we describe in the conceptual framework of the epigenetic landscape, with a view to bridging the gap between theory and practice at the patient's bedside...
December 1, 2016: Cancer Research
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