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Neuropharmacology

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https://www.readbyqxmd.com/read/29162430/spontaneous-activity-singly-bound-states-and-the-impact-of-alpha1phe64-mutation-on-gabaar-gating-in-the-novel-kinetic-model-based-on-the-single-channel-recordings
#1
Magdalena Kisiel, Magdalena Jatczak, Marek Brodzki, Jerzy W Mozrzymas
GABAA receptor is the primary mediator of inhibition in the adult mammalian brain. Our recent studies revealed that a classic gating scheme for GABAAR needed to be updated with an intermediate step (flipping) and that the α1Phe64 mutation at the GABA binding site affects this transition. However, description of flipping at the single-channel level remains incomplete. In particular, its role in singly-bound and spontaneous activity remains unknown. We have performed thus single-channel recordings over wide range of agonist concentration for wild-type α1β2γ2L receptors and α1Phe64 mutants...
November 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29162429/studies-with-psychedelic-drugs-in-human-volunteers
#2
REVIEW
Edward M Sellers, Myroslava K Romach, Deborah B Leiderman
Scientific curiosity and fascination have played a key role in human research with psychedelics along with the hope that perceptual alterations and heightened insight could benefit well-being and play a role in the treatment of various neuropsychiatric disorders. These motivations need to be tempered by a realistic assessment of the hurdles to be cleared for therapeutic use. Development of a psychedelic drug for treatment of a serious psychiatric disorder presents substantial although not insurmountable challenges...
November 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29155273/mu-opioid-peptide-mop-and-nociceptin-orphanin-fq-peptide-nop-receptor-activation-both-contribute-to-the-discriminative-stimulus-properties-of-cebranopadol-in-the-rat
#3
Thomas M Tzschentke, Kris Rutten
The novel potent analgesic cebranopadol is an agonist at nociceptin/orphanin FQ peptide (NOP) and classical opioid receptors, with the highest in-vitro activity at NOP and mu-opioid peptide (MOP) receptors, and somewhat lower activity at kappa-opioid peptide (KOP) and delta-opioid peptide (DOP) receptors. We addressed the question of which of these pharmacological activities contribute to the stimulus properties of cebranopadol using a rat drug discrimination procedure. First, cebranopadol was tested in generalization tests against a morphine cue, including receptor-specific antagonism...
November 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29154951/regulation-of-neural-ion-channels-by-muscarinic-receptors
#4
REVIEW
David A Brown
The excitable behaviour of neurons is determined by the activity of their endogenous membrane ion channels. Since muscarinic receptors are not themselves ion channels, the acute effects of muscarinic receptor stimulation on neuronal function are governed by the effects of the receptors on these endogenous neuronal ion channels. This review considers some principles and factors determining the interaction between subtypes and classes of muscarinic receptors with neuronal ion channels, and summarizes the effects of muscarinic receptor stimulation on a number of different channels, the mechanisms of receptor - channel transduction and their direct consequences for neuronal activity...
November 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29154773/neuropharmacology-of-venom-peptides
#5
EDITORIAL
David J Adams, Richard J Lewis
No abstract text is available yet for this article.
November 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29146504/minocycline-protects-developing-brain-against-ethanol-induced-damage
#6
Xin Wang, Kai Zhang, Fanmuyi Yang, Zhenhua Ren, Mei Xu, Jacqueline A Frank, Zun-Ji Ke, Jia Luo
Fetal alcohol spectrum disorders (FASD) are caused by ethanol exposure during the pregnancy and is the leading cause of mental retardation. Ethanol exposure during the development results in the loss of neurons in the developing brain, which may underlie many neurobehavioral deficits associated with FASD. It is important to understand the mechanisms underlying ethanol-induced neuronal loss and develop appropriate therapeutic strategies. One of the potential mechanisms involves neuroimmune activation. Using a third trimester equivalent mouse model of ethanol exposure, we demonstrated that ethanol induced a wide-spread neuroapoptosis, microglial activation, and neuroinflammation in C57BL/6 mice...
November 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29146505/muscarinic-receptor-oligomerization
#7
REVIEW
Sara Marsango, Richard J Ward, Elisa Alvarez-Curto, Graeme Milligan
G protein coupled receptors (GPCRs) have been classically described as monomeric entities that function by binding in a 1:1 stoichiometric ratio to both ligand and downstream signalling proteins. However, in recent years, a growing numbers of studies have supported the hypothesis that these receptors can interact to form dimers and higher order oligomers although the molecular basis for these interactions, the overall quaternary arrangements and the functional importance of the GPCR oligomerization remain topics of intense speculation...
November 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29146503/methodology-for-controlled-administration-of-smoked-synthetic-cannabinoids-jwh-018-and-jwh-073
#8
REVIEW
Ziva D Cooper, Justin L Poklis, Fei Liu
Synthetic cannabinoids (SCs) are a significant public health concern given their widespread use and severe effects associated with intoxication. However, there is a paucity of controlled human studies investigating the behavioral and physiological effects and pharmacokinetics of these compounds. Designing a reliable method to administer consistent, concentration-dependent synthetic cannabinoids is an integral component of controlled study of these compounds. Further, optimizing methods to assess the parent compounds and metabolites in plasma is critical in order to be able to establish their pharmacokinetics after administration...
November 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29146502/protracted-motivational-dopamine-related-deficits-following-adolescence-sugar-overconsumption
#9
Fabien Naneix, Florence Darlot, Véronique De Smedt-Peyrusse, Jean-Rémi Pape, Etienne Coutureau, Martine Cador
Adolescence represents a critical period characterized by major neurobiological changes. Chronic stimulation of the reward system during adolescence might constitute an important factor of vulnerability to pathological development. Increasing evidences suggest that adolescent overconsumption of sweet palatable foods impact reward-based processes. However, the neurobiological bases of these deficits remain poorly understood. Previous studies have demonstrated motivational deficits for palatable foods after sweet diet exposure during adolescence that might involve the dopamine (DA) system, a central actor in incentive processes...
November 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29102760/partial-inhibition-of-catecholamine-activity-and-enhanced-responsiveness-to-nmda-after-sustained-administration-of-vortioxetine
#10
Mohammad Ebrahimzadeh, Mostafa El Mansari, Pierre Blier
Vortioxetine is a multimodal drug that blocks serotonin (5-HT) reuptake and directly modulates 5-HT receptors. The effects of subacute and long-term administration of vortioxetine on various aspects of catecholamine and glutamate systems were investigated using single-unit extracellular recordings and microiontophoresis in the rat brain. The firing rate of dopamine (DA) neurons was significantly decreased (26%) after 14, but not 4 days of vortioxetine administration (vortioxetine-containing chow, 1.8 g/kg vortioxetine)...
November 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29138081/regulation-and-trafficking-of-muscarinic-acetylcholine-receptors
#11
REVIEW
Dmitry Zenko, James N Hislop
Fidelity of signal transduction relies on cells expressing the appropriate number of functional receptors. Fluctuation in the total number of muscarinic acetylcholine receptors has been implicated in a range of physiological and pathophysiological processes, and the mechanisms responsible for this regulation represent potential molecular targets for therapeutic intervention. This article will review the current literature on the endocytic trafficking of muscarinic receptors and how knowledge of the trafficking of related receptors might influence future studies...
November 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29138080/muscarinic-receptor-subtype-distribution-in-the-central-nervous-system-and-relevance-to-aging-and-alzheimer-s-disease
#12
REVIEW
E P Lebois, C Thorn, J R Edgerton, M Popiolek, S Xi
Muscarinic acetylcholine receptors (mAChRs) are G proteincoupled receptors (GPCRs) that mediate the metabotropic actions of acetylcholine (ACh). There are five subtypes of mAChR, M1 - M5, which are expressed throughout the central nervous system (CNS) on numerous cell types and represent promising treatment targets for a number of different diseases, disorders, and conditions of the CNS. Although the present review will focus on Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI), a number of conditions such as Parkinson's disease (PD), schizophrenia, and others represent significant unmet medical needs for which selective muscarinic agents could offer therapeutic benefits...
November 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29129776/glucagon-like-peptide-1-glp-1-and-neurotransmitters-signaling-in-epilepsy-an-insight-review
#13
REVIEW
Prashant Koshal, Sumit Jamwal, Puneet Kumar
Epilepsy is one of the most prevalent neurological disorder affecting more than 50 million people worldwide. Numerous studies have suggested that an imbalance in glutamatergic (excitatory) and GABAergic (inhibitory) neurotransmitter system is one of the dominating pathophysiological mechanisms underlying the occurrence and progression of seizures. Further, this alteration in GABAergic and glutamatergic system disrupts the delicate balance of other neurotransmitters system in the brain. Emerging strides have documented the protective role of GLP-1 signaling on altered neurotransmitters signaling in Epilepsy and associated co-morbidities...
November 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29129775/connecting-alzheimer-s-disease-to-diabetes-underlying-mechanisms-and-potential-therapeutic-targets
#14
REVIEW
Marcelo N N Vieira, Ricardo A S Lima-Filho, Fernanda G De Felice
Alzheimer's disease (AD) is a risk factor for type 2 diabetes and vice versa, and a growing body of evidence indicates that these diseases are connected both at epidemiological, clinical and molecular levels. Recent studies have begun to reveal common pathogenic mechanisms shared by AD and type 2 diabetes. Impaired neuronal insulin signaling and endoplasmic reticulum (ER) stress are present in animal models of AD, similar to observations in peripheral tissue in T2D. These findings shed light into novel diabetes-related mechanisms leading to brain dysfunction in AD...
November 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29129774/crosstalk-between-endoplasmic-reticulum-stress-and-brain-inflammation-in-alzheimer-s-disease
#15
REVIEW
Luis E Santos, Sergio T Ferreira
While most often noted for its cognitive symptoms, Alzheimer's disease (AD) is, at its core, a disease of protein misfolding/aggregation, with an intriguing inflammatory component. Defective clearance and/or abnormal production of the amyloid-β peptide (Aβ), and its ensuing accumulation and aggregation, underlie two hallmark features of AD: brain accumulation of insoluble protein deposits known as amyloid or senile plaques, and buildup of soluble Aβ oligomers (AβOs), diffusible toxins linked to synapse dysfunction and memory impairment...
November 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29128308/oxidative-stress-and-dna-damage-after-cerebral-ischemia-potential-therapeutic-targets-to-preserve-the-genome-and-improve-stroke-recovery
#16
REVIEW
Peiying Li, R Anne Stetler, Rehana K Leak, Yejie Shi, Yan Li, Weifeng Yu, Michael V L Bennett, Jun Chen
The past two decades have witnessed remarkable advances in oxidative stress research, particularly in the context of ischemic brain injury. Oxidative stress in ischemic tissues compromises the integrity of the genome, resulting in DNA lesions, cell death in neurons, glial cells, and vascular cells, and impairments in neurological recovery after stroke. As DNA is particularly vulnerable to oxidative attack, cells have evolved the ability to induce multiple DNA repair mechanisms, including base excision repair (BER), nucleotide excision repair (NER) and non-homogenous endpoint jointing (NHEJ)...
November 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29128307/rescue-of-glutamate-transport-in-the-lateral-habenula-alleviates-depression-and-anxiety-like-behaviors-in-ethanol-withdrawn-rats
#17
Seungwoo Kang, Jing Li, Alex Bekker, Jiang-Hong Ye
Alcoholism and psychiatric disorders like depression and anxiety are often comorbid. Although the mechanisms underlying this comorbidity are unclear, emerging evidence suggests that maladaptation of the glial glutamate transporter GLT-1 may play a role. Findings from animal and human studies have linked aversive states, including those related to drugs of abuse and depression, to aberrant activity in the lateral habenula (LHb). The relationship between GLT-1 maladaptation, LHb activity, and abnormal behaviors related to alcohol withdrawal, however, remains unknown...
November 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29128306/norman-bowery-s-discoveries-about-extrasynaptic-and-asynaptic-gaba-systems-and-their-significance
#18
REVIEW
David A Brown
Before discovering the GABA-B receptor, Norman Bowery completed a series of studies on an extrasynaptic or asynaptic "GABA system" in the rat superior cervical sympathetic ganglion. First, he discovered an uptake system for GABA in neuroglial cells in the ganglia and in peripheral nerves, with a different substrate specificity than that in neurons. Second, he showed that accumulated GABA in sympathetic glial cells was metabolized to succinate by a transaminase enzyme. Third, he provided detailed structure-activity information about compounds activating an extrasynaptic GABA-A receptor on neurons in the rat sympathetic ganglion...
November 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29128305/methamphetamine-induced-impulsivity-during-chronic-methamphetamine-treatment-in-rats-effects-of-the-taar-1-agonist-ro5263397
#19
Zhaoxia Xue, Justin N Siemian, Bernard N Johnson, Yanan Zhang, Jun-Xu Li
Impulsivity is an important personality trait associated with several clinical syndromes including drug abuse. While repeated drug exposure is known to increase certain behavioral responses, such as locomotion, to subsequent drug exposure, few studies have examined whether such sensitization develops for impulsive behavior. In the current study we tested the effects of methamphetamine acutely, during the course of, and upon discontinuation of chronic methamphetamine treatment on impulsive behavior in two models, the 5-choice serial reaction time task (5-CSRTT) and the delay-discounting task which measure impulsive action and impulsive choice, respectively...
November 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29126910/impaired-oligodendrogenesis-and-myelination-by-elevated-s100b-levels-during-neurodevelopment
#20
Gisela Santos, Andreia Barateiro, Cláudio M Gomes, Dora Brites, Adelaide Fernandes
High levels of the inflammatory molecule S100B protein have been identified in sera from several perinatal inflammatory conditions involving myelin damage and associated with an adverse prognosis or the emergence of sequelea. S100B is essential for oligodendrocyte (OL) differentiation and maturation, but it remains to be established if excessive levels of released S100B upon early brain injury are deleterious in the neurodevelopmental period. Here, we investigated this possibility by evaluating how elevated S100B affects oligodendrogenesis during this period...
November 8, 2017: Neuropharmacology
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