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https://www.readbyqxmd.com/read/28647359/mild-hypothermia-ameliorates-muscle-wasting-in-septic-rats-associated-with-hypothalamic-ampk-induced-autophagy-and-neuropeptides
#1
Chun Cao, Tao Gao, Minhua Cheng, Fengchan Xi, Chenyan Zhao, Wenkui Yu
Sepsis, always developing muscle wasting, contributes to serious complications and mortality. Mild hypothermia has been reported to have protective effects on the prognosis of septic patients. However, the underlying mechanisms remain unclear. We therefore hypothesized that mild hypothermia could ameliorate muscle wasting during sepsis and whether it was associated with hypothalamus AMPK-induced autophagy and neuropeptides. Adult male Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) (5 mg/kg) or saline...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28634445/antioxidant-treatment-with-n-acetyl-cysteine-prevents-the-development-of-cognitive-and-social-behavioral-deficits-that-result-from-perinatal-ketamine-treatment
#2
Aarron Phensy, Hasmik E Duzdabanian, Samantha Brewer, Anurag Panjabi, Christopher Driskill, Annuska Berz, George Peng, Sven Kroener
Alterations of the normal redox state can be found in all stages of schizophrenia, suggesting a key role for oxidative stress in the etiology and maintenance of the disease. Pharmacological blockade of N-methyl-D-aspartic acid (NMDA) receptors can disrupt natural antioxidant defense systems and induce schizophrenia-like behaviors in animals and healthy human subjects. Perinatal administration of the NMDA receptor (NMDAR) antagonist ketamine produces persistent behavioral deficits in adult mice which mimic a range of positive, negative, and cognitive symptoms that characterize schizophrenia...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28623171/broad-analgesic-activity-of-a-novel-selective-m1-agonist
#3
Michael W Wood, Giovanni Martino, Martin Coupal, Mattias Lindberg, Patricia Schroeder, S Santhakumar, Manon Valiquette, Johan Sandin, Daniel Widzowski, Jennifer Laird
Although the muscarinic receptor family has long been a source of potentially compelling targets for small molecule drug discovery, it was difficult to achieve agonist selectivity within the family. A new class of M1 muscarinic agonists has emerged, and these compounds have been characterized as agonists that activate the receptor at an allosteric site. Members of this class of M1 agonists have been shown to be selective across the muscarinic receptors. However, upon introduction of a novel pharmacologic mechanism, it is prudent to ensure that no new off-target activities have arisen, particularly within the context of in vivo experiments...
June 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28618002/novel-psychoactive-substance-use-among-treatment-seeking-opiate-users-the-role-of-life-events-and-psychiatric-symptoms
#4
Máté Kapitány-Fövény, Judit Farkas, Patrícia Andrea Pataki, Anna Kiss, Janka Horváth, Róbert Urbán, Zsolt Demetrovics
OBJECTIVE: Over the past 5 years, a shift to the use of novel psychoactive substances (NPS) has been observed among opioid users. The aim of this study was to assess the potential reasons for NPS use among treatment-seeking patients receiving opiate substitution therapy. METHOD: A structured questionnaire was filled out by a sample of 198 opiate dependent patients of Hungary's National Institute of Psychiatry and Addiction. This questionnaire assessed demographics, treatment characteristics, lifetime substance use, potential reasons for NPS use, negative life events (Life Events Scale), and psychiatric symptoms (Brief Symptom Inventory)...
June 15, 2017: Human Psychopharmacology
https://www.readbyqxmd.com/read/28593999/a-novel-pkc-inhibitor-shows-promise-for-amphetamine-use-disorders
#5
Amy Hauck Newman
Neuropsychopharmacology accepted article preview online, 08 June 2017. doi:10.1038/npp.2017.116.
June 8, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28589265/effects-of-ketamine-on-the-unconditioned-and-conditioned-locomotor-activity-of-preadolescent-and-adolescent-rats-impact-of-age-sex-and-drug-dose
#6
Sanders A McDougall, Andrea E Moran, Timothy J Baum, Matthew G Apodaca, Vanessa Real
RATIONALE: Ketamine is used by preadolescent and adolescent humans for licit and illicit purposes. OBJECTIVE: The goal of the present study was to determine the effects of acute and repeated ketamine treatment on the unconditioned behaviors and conditioned locomotor activity of preadolescent and adolescent rats. METHODS: To assess unconditioned behaviors, female and male rats were injected with ketamine (5-40 mg/kg), and distance traveled was measured on postnatal day (PD) 21-25 or PD 41-45...
June 7, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28588509/behavioral-effects-of-a-novel-benzofuranyl-piperazine-serotonin-2c-receptor-agonist-suggest-a-potential-therapeutic-application-in-the-treatment-of-obsessive-compulsive-disorder
#7
Michelle M Rodriguez, Carl Overshiner, J David Leander, Xia Li, Denise Morrow, Richard G Conway, David L Nelson, Karin Briner, Jeffrey M Witkin
Selective serotonin reuptake inhibitors (SSRIs) are the only effective pharmacological treatments for obsessive-compulsive disorder (OCD). Nonetheless, their generally limited efficacy, side-effects, and delayed onset of action require improved medications for this highly prevalent disorder. Preclinical and clinical findings have suggested serotonin2C (5-HT2C) receptors as a potential drug target. Data in rats and mice are presented here on the effects of a novel 5-HT2C receptor agonist ((3S)-3-Methyl-1-[4-(trifluoromethyl)-7-benzofuranyl]-piperazine) (CPD 1) with high potency and full efficacy at 5-HT2C receptors and less potency and partial agonism at 5-HT2A and 5-HT2B receptors...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28571709/phospho-specific-antibodies-targeting-the-amino-terminus-of-the-human-dopamine-transporter
#8
Caline S Karam, Namita Sen, Jonathan A Javitch
The dopamine transporter (DAT), which mediates the inactivation of released dopamine through its reuptake, is the primary molecular target for the actions of psychostimulants. An increasing number of studies support an essential role for phosphorylation of serines (Ser) in the distal amino (N) terminus of DAT in regulating its function. Still, the molecular details of the regulation of phosphorylation and its impact on function are not fully understood. To address this, we have developed and characterized two distinct phospho-antibodies that recognize human DAT when it is phosphorylated at Ser7 or Ser12...
May 30, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28544816/analytical-characterization-of-three-cathinone-derivatives-4-mpd-4%C3%A2-f-php-and-bk-epdp-purchased-as-bulk-powder-from-online-vendors
#9
Orapan Apirakkan, Anca Frinculescu, Trevor Shine, Mark C Parkin, Agostino Cilibrizzi, Nunzianda Frascione, Vincenzo Abbate
Novel emerging drugs of abuse, also referred as new psychoactive substances (NPS), constitute an ever-changing mixture of chemical compounds designed to circumvent legislative controls by means of chemical modifications of previously banned recreational drugs. One of such class, synthetic cathinones, namely β-keto derivatives of amphetamines, has been largely abused over the past decade. A number of new synthetic cathinones are detected each year, either in bulk powders/crystals or in biological matrices. It is therefore important to continuously monitor the supply of new synthetic derivatives and promptly report them...
May 23, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28535130/home-manufacture-of-drugs-an-online-investigation-and-a-toxicological-reality-check-of-online-discussions-on-drug-chemistry
#10
Evelyn Hearne, Emanuele Amorim Alves, Marie Claire Van Hout, Jean-Paul C Grund
Emerging trends in market dynamics and the use of new psychoactive substances are both a public health concern and a complex regulatory issue. One novel area of investigation is the availability of homemade opioids, amphetamines and dissociatives, and the potential fueling of interest in clandestine home manufacture of drugs via the Internet. We illustrate here how online communal folk pharmacology of homemade drugs on drug website forums may actually inform home manufacture practices or contribute to the reduction of harms associated with this practice...
May 23, 2017: Journal of Psychoactive Drugs
https://www.readbyqxmd.com/read/28522253/challenges-in-the-development-of-an-m4-pam-preclinical-candidate-the-discovery-sar-and-in-vivo-characterization-of-a-series-of-3-aminoazetidine-derived-amides
#11
James C Tarr, Michael R Wood, Meredith J Noetzel, Jeanette L Bertron, Rebecca L Weiner, Alice L Rodriguez, Atin Lamsal, Frank W Byers, Sichen Chang, Hyekyung P Cho, Carrie K Jones, Colleen M Niswender, Michael W Wood, Nicholas J Brandon, Mark E Duggan, P Jeffrey Conn, Thomas M Bridges, Craig W Lindsley
This letter details the continued chemical optimization of a novel series of M4 positive allosteric modulators (PAMs) based on a 5-amino-thieno[2,3-c]pyridazine core by incorporating a 3-amino azetidine amide moiety. The analogs described within this work represent the most potent M4 PAMs reported for this series to date. The SAR to address potency, clearance, subtype selectivity, CNS exposure, and P-gp efflux are described. This work culminated in the discovery of VU6000918, which demonstrated robust efficacy in a rat amphetamine-induced hyperlocomotion reversal model at a minimum efficacious dose of 0...
July 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28516232/-cns-metabolism-in-high-risk-drug-abuse-german-version-insights-gained-from-1-h-and-31-p-mrs-and-pet
#12
REVIEW
S V Bodea
BACKGROUND: High-risk drug consumption is a considerable problem for public health actors in industrialised countries. The latest trends show a market tendency towards diversification and increasing demand for high-purity synthetic drugs. Whilst most consumers seek medical help after cannabis use, it is high-risk drugs like cocaine, heroin and amphetamines that account for most of the 1000 drug-related deaths that occur in Germany every year. PURPOSE: This article presents the most prominent in vivo cerebral metabolic information in cocaine, heroin and methamphetamine users provided by MRI spectroscopy and PET imaging...
June 2017: Der Radiologe
https://www.readbyqxmd.com/read/28506818/measuring-inhibition-of-monoamine-reuptake-transporters-by-new-psychoactive-substances-nps-in-real-time-using-a-high-throughput-fluorescence-based-assay
#13
Anne Zwartsen, Anouk H A Verboven, Regina G D M van Kleef, Fiona M J Wijnolts, Remco H S Westerink, Laura Hondebrink
The prevalence and use of new psychoactive substances (NPS) is increasing and currently over 600 NPS exist. Many illicit drugs and NPS increase brain monoamine levels by inhibition and/or reversal of monoamine reuptake transporters (DAT, NET and SERT). This is often investigated using labor-intensive, radiometric endpoint measurements. We investigated the applicability of a novel and innovative assay that is based on a fluorescent monoamine mimicking substrate. DAT, NET or SERT-expressing human embryonic kidney (HEK293) cells were exposed to common drugs (cocaine, dl-amphetamine or MDMA), NPS (4-fluoroamphetamine, PMMA, α-PVP, 5-APB, 2C-B, 25B-NBOMe, 25I-NBOMe or methoxetamine) or the antidepressant fluoxetine...
May 12, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28424564/new-developments-in-the-management-of-narcolepsy
#14
REVIEW
Vivien C Abad, Christian Guilleminault
Narcolepsy is a life-long, underrecognized sleep disorder that affects 0.02%-0.18% of the US and Western European populations. Genetic predisposition is suspected because of narcolepsy's strong association with HLA DQB1*06-02, and genome-wide association studies have identified polymorphisms in T-cell receptor loci. Narcolepsy pathophysiology is linked to loss of signaling by hypocretin-producing neurons; an autoimmune etiology possibly triggered by some environmental agent may precipitate hypocretin neuronal loss...
2017: Nature and Science of Sleep
https://www.readbyqxmd.com/read/28390877/effects-of-chronic-prenatal-mk-801-treatment-on-object-recognition-cognitive-flexibility-and-drug-induced-locomotor-activity-in-juvenile-and-adult-rat-offspring
#15
S Gallant, L Welch, P Martone, U Shalev
BACKGROUND: Patients with schizophrenia display impaired cognitive functioning and increased sensitivity to psychomimetic drugs. The neurodevelopmental hypothesis of schizophrenia posits that disruption of the developing brain predisposes neural networks to lasting structural and functional abnormalities resulting in the emergence of such symptoms in adulthood. Given the critical role of the glutamatergic system in early brain development, we investigated whether chronic prenatal exposure to the glutamate NMDA receptor antagonist, MK-801, induces schizophrenia-like behavioural and neurochemical changes in juvenile and adult rats...
April 6, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28373127/rp5063-an-atypical-antipsychotic-drug-with-a-unique-pharmacologic-profile-improves-declarative-memory-and-psychosis-in-mouse-models-of-schizophrenia
#16
Lakshmi Rajagopal, Sunoh Kwon, Mei Huang, Eric Michael, Laxminarayan Bhat, Marc Cantillon, Herbert Y Meltzer
Various types of atypical antipsychotic drugs (AAPDs) modestly improve the cognitive impairment associated with schizophrenia (CIAS). RP5063 is an AAPD with a diverse and unique pharmacology, including partial agonism at dopamine (DA) D2, D3, D4, serotonin (5-HT)1A, and 5-HT2A receptors (Rs), full agonism at α4β2 nicotinic acetylcholine (ACh)R (nAChR), and antagonism at 5-HT2B, 5-HT6, and 5-HT7Rs. Most atypical APDs are 5-HT2A inverse agonists. The efficacy of RP5063 in mouse models of psychosis and episodic memory were studied...
March 31, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28332334/-apaan-in-the-neck-a-reflection-on-some-novel-impurities-found-in-seized-materials-containing-amphetamine-in-ireland-during-routine-forensic-analysis
#17
John D Power, Pierce Kavanagh, Gavin McLaughlin, Michael Barry, Geraldine Dowling, Simon D Brandt
No abstract text is available yet for this article.
March 23, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28322273/neuregulin-2-ablation-results-in-dopamine-dysregulation-and-severe-behavioral-phenotypes-relevant-to-psychiatric-disorders
#18
L Yan, A Shamir, M Skirzewski, E Leiva-Salcedo, O B Kwon, I Karavanova, D Paredes, O Malkesman, K R Bailey, D Vullhorst, J N Crawley, A Buonanno
Numerous genetic and functional studies implicate variants of Neuregulin-1 (NRG1) and its neuronal receptor ErbB4 in schizophrenia and many of its endophenotypes. Although the neurophysiological and behavioral phenotypes of NRG1 mutant mice have been investigated extensively, practically nothing is known about the function of NRG2, the closest NRG1 homolog. We found that NRG2 expression in the adult rodent brain does not overlap with NRG1 and is more extensive than originally reported, including expression in the striatum and medial prefrontal cortex (mPFC), and therefore generated NRG2 knockout mice (KO) to study its function...
March 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28303900/associations-between-behavioral-and-neural-correlates-of-inhibitory-control-and-amphetamine-reward-sensitivity
#19
Jessica Weafer, Stephanie M Gorka, Donald Hedeker, Mario Dzemidzic, David A Kareken, K Luan Phan, Harriet de Wit
Poor inhibitory control and sensitivity to drug reward are two significant risk factors for drug abuse. Although the two have been largely viewed as separate and independent risk factors, there is new evidence to suggest that they may be related at both the behavioral and neural level. This study examined associations between behavioral and neural correlates of inhibitory control and sensitivity to the subjective rewarding effects of amphetamine in humans. Healthy volunteers (n=63) first completed the stop signal task, a behavioral measure of inhibitory control...
March 17, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28294132/5-ht2c-agonists-modulate-schizophrenia-like-behaviors-in-mice
#20
Vladimir M Pogorelov, Ramona M Rodriguiz, Jianjun Cheng, Mei Huang, Claire M Schmerberg, Herbert Y Meltzer, Bryan L Roth, Alan P Kozikowski, William C Wetsel
All FDA-approved antipsychotic drugs (APDs) target primarily dopamine D2 or serotonin (5-HT2A) receptors, or both; however, these medications are not universally effective, they may produce undesirable side effects, and provide only partial amelioration of negative and cognitive symptoms. The heterogeneity of pharmacological responses in schizophrenic patients suggests that additional drug targets may be effective in improving aspects of this syndrome. Recent evidence suggests that 5-HT2C receptors may be a promising target for schizophrenia since their activation reduces mesolimbic nigrostriatal dopamine release (which conveys antipsychotic action), they are expressed almost exclusively in CNS, and have weight-loss-promoting capabilities...
April 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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