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Gerhard Rammes, Franziska Seeser, Korinna Mattusch, Kaichuan Zhu, Laura Haas, Markus Kummer, Michael Heneka, Jochen Herms, Chris G Parsons
Aβ1-42 is well accepted to be a primary early pathogenic agent in Alzheimer's disease (AD). However, other amyloid peptides are now gaining considerable attention as potential key participants in AD due to their proposed higher neuronal toxicity. Impairment of the glutamatergic system is also widely accepted to be associated with pathomechanisms underlying AD. There is ample evidence that Aβ1-42 affects GLUN2B subunit containing N-methyl-D-aspartate receptor function and abolishes the induction of long term potentiation (LTP)...
July 14, 2018: Neuropharmacology
Erbo Dong, Alessandro Guidotti, Huaibo Zhang, Subhash C Pandey
Currently, the etiology of anxiety comorbid with alcohol use disorder (AUD) remains to be elucidated. Epidemiologic evidence suggests that individuals during their prenatal development may be especially vulnerable to the effects of environmental factors such as stress that predisposes them to psychiatric disorders including AUD later in life. To explore the cause of the comorbidity, we examined anxiety-like and alcohol drinking behaviors in adult offspring of prenatally stressed dam (referred as PRS-mice) using well-characterized paradigms-elevated plus maze (EPM), light/dark box (LDB) and two-bottle free-choice...
July 14, 2018: Neuropharmacology
Pi-Chuan Fan, Tzu-Hsuan Lai, Chia Chun Hor, Ming Tatt Lee, Pokai Huang, Werner Sieghart, Margot Ernst, Daniel E Knutson, James Cook, Lih-Chu Chiou
Novel treatments against migraine are an urgent medical requirement. α6 subunit-containing GABAA receptors (α6GABAA Rs) are expressed in trigeminal ganglia (TG), the hub of the trigeminal vascular system (TGVS) that is involved in the pathogenesis of migraine. Here we reveal an unprecedented role of α6GABAA Rs in ameliorating TGVS activation using several pharmacological approaches in an animal model mimicking pathological changes in migraine. TGVS activation was induced by intra-cisternal (i.c.) instillation of capsaicin in Wistar rats...
July 14, 2018: Neuropharmacology
Caitlin A Orsini, Sara C Heshmati, Tyler S Garman, Shannon C Wall, Jennifer L Bizon, Barry Setlow
The prefrontal cortex (PFC) plays an important role in several forms of cost-benefit decision making. Its contributions to decision making under risk of explicit punishment, however, are not well understood. A rat model was used to investigate the role of the medial PFC (mPFC) and its monoaminergic innervation in a Risky Decision-making Task (RDT), in which rats chose between a small, "safe" food reward and a large, "risky" food reward accompanied by varying probabilities of mild footshock punishment...
July 13, 2018: Neuropharmacology
Andrew M Lamade, Elizabeth M Kenny, Tamil S Anthonymuthu, Elif Soysal, Robert Clark, Valerian E Kagan, Hülya Bayır
Mitochondria are a keystone of neuronal function, serving a dual role as sustainer of life and harbinger of death. While mitochondria are indispensable for energy production, a dysregulated mitochondrial network can spell doom for both neurons and the functions they provide. Traumatic brain injury (TBI) is a complex and biphasic injury, often affecting children and young adults. The primary pathological mechanism of TBI is mechanical, too rapid to be mitigated by anything but prevention. However, the secondary injury of TBI evolves over hours and days after the initial insult providing a window of opportunity for intervention...
July 12, 2018: Neuropharmacology
Charles L C Smelt, Victoria R Sanders, Joseph Newcombe, Richard P Burt, Tom D Sheppard, Maya Topf, Neil S Millar
Several previous studies have demonstrated that the activity of neurotransmitters acting on ligand-gated ion channels such as the nicotinic acetylcholine receptor (nAChR) can be altered by compounds binding to allosteric modulatory sites. In the case of α7 nAChRs, both positive and negative allosteric modulators (PAMs and NAMs) have been identified and have attracted considerable interest. A recent study, employing revised structural models of the transmembrane domain of the α7 nAChR in closed and open conformations, has provided support for an inter-subunit transmembrane allosteric binding site (Newcombe et al 2017)...
July 12, 2018: Neuropharmacology
Yi Ye, Nicole N Scheff, Daniel Bernabé, Elizabeth Salvo, Kentaro Ono, Cheng Liu, Ratna Veeramachaneni, Chi T Viet, Dan T Viet, John C Dolan, Brian L Schmidt
Oral cancer is often painful and lethal. Oral cancer progression and pain may result from shared pathways that involve unresolved inflammation and elevated levels of pro-inflammatory cytokines. Resolvin D-series (RvDs) are endogenous lipid mediators derived from omega-3 fatty acids that exhibit pro-resolution and anti-inflammatory actions. These mediators have recently emerged as a novel class of therapeutics for diseases that involve inflammation; the specific roles of RvDs in oral cancer and associated pain are not defined...
July 12, 2018: Neuropharmacology
Christian M Wood, Keith A Wafford, Andrew P McCarthy, Nicola Hewes, Elaine Shanks, David Lodge, Emma Sj Robinson
Group II metabotropic glutamate receptors (mGluR2 and mGluR3) are implicated in a number of psychiatric disorders. They also control sleep-wake architecture and may offer novel therapeutic targets. However, the roles of the mGluR2 versus mGluR3 subtypes are not well understood. Here, we have taken advantage of the recently described mutant strain of Han Wistar rats, which do not express mGluR2 receptors, to investigate behavioural, sleep and EEG responses to mGluR2/3 ligands. The mGluR2/3 agonist, LY354740 (10 mg/kg), reversed amphetamine- and phencyclidine-induced locomotion and rearing behaviours in control Wistar but not in mGluR2 lacking Han Wistar rats...
July 10, 2018: Neuropharmacology
Maureen L Petrunich-Rutherford, Francisca Garcia, George Battaglia
Increasing evidence suggests that multiple factors can produce effects on the immature brain that are distinct and more long-lasting than those produced in adults. The hypothalamic paraventricular nucleus (PVN) is a region integral to the hypothalamic-pituitary-adrenal axis and is affected by anxiety, depression, and drugs used to treat these disorders, yet receptor signaling mechanisms operative in hypothalamus prior to maturation remain to be elucidated. In peripubertal male rats, systemic injection of the selective serotonin 1A (5-HT1A ) receptor agonist (+)8-OH-DPAT (0...
July 10, 2018: Neuropharmacology
Maria Berrocal, Isaac Corbacho, Carlos Gutierrez-Merino, Ana M Mata
The phenothiazine methylene blue (MB) is attracting increasing attention because it seems to have beneficial effects in the pathogenesis of Alzheimer's disease (AD). Among other factors, the presence of neuritic plaques of amyloid-β peptide (Aβ) aggregates, neurofibrilar tangles of tau and perturbation of cytosolic Ca2+ are important players of the disease. It has been proposed that MB decreases the formation of neuritic plaques due to Aβ aggregation. However, the molecular mechanism underlying this effect is far from clear...
July 9, 2018: Neuropharmacology
Jing Wen, Rochelle R Maxwell, Alexander J Wolf, Menachem Spira, Maria E Gulinello, Peter D Cole
Methotrexate is a dihydrofolate reductase inhibitor widely employed in curative treatment for children with acute lymphoblastic leukemia (ALL). However, methotrexate administration is also associated with persistent cognitive deficits among long-term childhood cancer survivors. Animal models of methotrexate-induced cognitive deficits have primarily utilized adult animals. The purpose of present study is to investigate the neurotoxicity of methotrexate in juvenile rats and its relevant mechanisms. The doses and schedule of systemic and intrathecal methotrexate, given from post-natal age 3-7 weeks, were chosen to model the effects of repeated methotrexate dosing on the developing brains of young children with ALL...
July 7, 2018: Neuropharmacology
Anil Kumar Rana, Damanpreet Singh
Cerebral stroke is a leading cause of early death and physical disability in adults throughout the world. Oxidative stress and inflammation plays an important role in the pathological process associated with the stroke. The available reperfusion therapy itself enhances the oxidative stress by overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) from the neurons, as well as non-neuronal cells, thus further worsens the condition. Excessive ROS and RNS production contributes to the brain injury during or after the stroke by activating inflammatory processes...
July 6, 2018: Neuropharmacology
Ágota A Biró, Antoine Brémaud, Joanne Falck, Arnaud J Ruiz
A-type K+ channels restrain the spread of incoming signals in tufted and apical dendrites of pyramidal neurons resulting in strong compartmentalization. However, the exact subunit composition and functional significance of K+ channels expressed in small diameter proximal dendrites remain poorly understood. We focus on A-type K+ channels expressed in basal and oblique dendrites of cortical layer 3 pyramidal neurons, in ex vivo brain slices from young adult mice. Blocking putative Kv4 subunits with phrixotoxin-2 enhances depolarizing potentials elicited by uncaging RuBi-glutamate at single dendritic spines...
July 6, 2018: Neuropharmacology
Azadeh Sabetghadam, Agnieszka Grabowiecka-Nowak, Alan Kania, Anna Gugula, Ewa Blasiak, Tomasz Blasiak, Sherie Ma, Andrew L Gundlach, Anna Blasiak
The rat nucleus incertus (NI) contains GABA/peptide-projection neurons responsive to orexin (hypocretin)/orexin receptor-2 (OX2 ) signalling. Melanin-concentrating hormone (MCH) and orexin neurons often innervate and influence common target areas. Therefore, we assessed the relationship between these hypothalamic peptidergic systems and rat NI, by investigating the presence of an MCH innervation and MCH receptor-1 (MCH1 ) expression, and neurophysiological and behavioural effects of MCH c.f. orexin-A (OXA), within the NI...
July 5, 2018: Neuropharmacology
Yatendra Mulpuri, Vincent N Marty, Joseph J Munier, Ken Mackie, Brian L Schmidt, Herbert H Seltzman, Igor Spigelman
Chemotherapy-induced peripheral neuropathy (CIPN) is a severe and dose-limiting side effect of cancer treatment that affects millions of cancer survivors throughout the world and current treatment options are extremely limited by their side effects. Cannabinoids are highly effective in suppressing pain symptoms of chemotherapy-induced and other peripheral neuropathies but their widespread use is limited by central nervous system (CNS)-mediated side effects. Here, we tested one compound from a series of recently developed synthetic peripherally restricted cannabinoids (PRCBs) in a rat model of cisplatin-induced peripheral neuropathy...
July 4, 2018: Neuropharmacology
Mengbing Huang, Chen Yan, Xiaoyan Yang, Xiaoshuang Zhou, Wei Lv, Ningning Guo, Ye Li, Jie Bai
Relapse of drug abuse after abstinence is a major challenge to the treatment of addicts. Thioredoxin-1 (Trx-1) is an important regulator of neuroprotection, and inhibits morphine-induced hyperlocomotion, reward and withdrawal signs, as well as blocks methamphetamine (METH)-induced conditioned place preference (CPP). Nucleus accumbens (NAc) is essential for relapse like behavior in reinstatement animal models. In the present study, we aim to investigate the role of Trx-1 in NAc in METH-primed reinstatement by using a reinstatement procedure in mice...
July 4, 2018: Neuropharmacology
Martial Caillaud, Benjamin Chantemargue, Laurence Richard, Laetitia Vignaud, Frédéric Favreau, Pierre-Antoine Faye, Philippe Vignoles, Franck Sturtz, Patrick Trouillas, Jean-Michel Vallat, Alexis Desmoulière, Fabrice Billet
Traumatic injuries to peripheral nerves are frequent, however, specific pharmacological treatments are currently lacking. Curcumin has antioxidant, anti-inflammatory and neuroprotective properties but high oral doses are required for therapeutic use, particularly due to its low bioavailability. The aim of the present study was to investigate the effects of local and continuous treatment using low curcumin doses on functional recovery and nerve regeneration after rat sciatic nerve crush (SNC). Curcumin was administered by osmotic pumps with a catheter delivering the drug at the injury site (0...
July 3, 2018: Neuropharmacology
Adjia Hamadjida, Stephen G Nuara, Dominique Bedard, Fleur Gaudette, Francis Beaudry, Jim C Gourdon, Philippe Huot
Blockade of serotonin 2A (5-HT2A ) receptors is regarded as an anti-dyskinetic and anti-psychotic strategy in Parkinson's disease (PD). However, the 5-HT2A antagonists tested so far exhibited affinity for other receptors, which might have played a role in their action. EMD-281,014 is the most selective 5-HT2A antagonist available, with approximately 2,000-fold selectivity over serotonin 2C (5-HT2C ) receptors. EMD-281,014 was previously tested in the clinic and has high translational potential. In the present study, we assessed the effect of EMD-281,014 on dyskinesia and psychosis in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned common marmoset...
June 30, 2018: Neuropharmacology
Henrik Jungaberle, Sascha Thal, Andrea Zeuch, Ansgar Rougemont-Bücking, Maximilian von Heyden, Helena Aicher, Milan Scheidegger
RATIONALE: We reviewed the concepts and empirical findings in studies with psychedelics and entactogens related to positive psychology - the study of healthy human functioning, well-being and eudaemonia. It is an unresolved question how beneficial effects of psychedelics and entactogens are related to the potential risks of these substances - particularly in non-clinical settings. METHODS: We searched in PubMed, PsychINFO and the Cochrane Library for controlled clinical and epidemiological studies which applied concepts from positive psychology...
June 29, 2018: Neuropharmacology
Gubbi Govindaiah, Young-Jin Kang, Hannah Elisabeth Smashey Lewis, Leeyup Chung, Ethan M Clement, Lazar John Greenfield, Edgar Garcia-Rill, Sang-Hun Lee
GABAergic interneurons in the hippocampus are critically involved in almost all hippocampal circuit functions including coordinated network activity. Somatostatin-expressing oriens-lacunosum moleculare (O-LM) interneurons are a major subtype of dendritically projecting interneurons in hippocampal subregions (e.g., CA1), and express group I metabotropic glutamate receptors (mGluRs), specifically mGluR1 and mGluR5 . Group I mGluRs are thought to regulate hippocampal circuit functions partially through GABAergic interneurons...
June 28, 2018: Neuropharmacology
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