Abstract:
:Phosphodiesterase 2 (PDE2) plays an important role in treatment of stress-related depression through regulation of antioxidant defense and neuroprotective mechanisms. However, the causal relationship between PDE2 and the prevalence of depression and anxiety upon exposure to oxidative stress has not been investigated. The present study examined whether the effects of PDE2 inhibition on oxidative stress were directly involved in reduced ROS by regulating NADPH subunits gp91phox oxidase. The results suggested that the PDE2 inhibitor Bay 60-7550 reversed oxidative stress-induced behavioral signature, i.e. depression and anxiety. Pretreatment with the oxidizing agent DTNB completely blocked, while the reducing agent DTT and the NADPH oxidase inhibitor apocynin potentiated the effects of Bay 60-7550 on behavioral abnormalities, demonstrating the relationship between PDE2 and oxidative stress. Consistently, an in vitro test revealed the positive correlation between ROS and PDE2 levels. Moreover, Bay 60-7550 decreased corticosterone-induced gp91phox expression, which is the source of ROS. The subsequent study suggested that Bay 60-7550 induced decrease in ROS and increase in cAMP/cGMP, pVASP, pCREB, and the neurotrophic factor BDNF levels, which were completely blocked by CRISPR/Cas9-mediated gp91phox overexpression and potentiated by gp91phox siRNA-based antioxidant strategies. The in vivo test in stressed mice further suggested that gp91phox overexpression completely blocked the antidepressant- and anxiolytic-like effects of Bay 60-7550, while gp91phox knockdown enhanced such effects. These results provide solid evidence that the antidepressant- and anxiolytic-like effects of Bay 60-7550 against stress are causally related to down-regulation of gp91phox and activation of the cAMP/cGMP-pVASP-CREB-BDNF signaling pathway.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Huang X,Xiaokaiti Y,Yang J,Pan J,Li Z,Luria V,Li Y,Song G,Zhu X,Zhang HT,O'Donnell JM,Xu Ydoi
10.1016/j.neuropharm.2018.09.039subject
Has Abstractpub_date
2018-12-01 00:00:00pages
176-185eissn
0028-3908issn
1873-7064pii
S0028-3908(18)30708-1journal_volume
143pub_type
杂志文章abstract:INTRODUCTION:The aim of the study was to clarify the dose response for inhibition of catechol-O-methyltransferase (COMT) by opicapone, a third generation COMT inhibitor, after acute and repeated administration to the cynomolgus monkey with pharmacokinetic evaluation at the higher dose. METHODS:Three cynomolgus monkeys...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2018.10.001
更新日期:2018-12-01 00:00:00
abstract::Current antipsychotic drugs (APDs) act on D2 receptors, and preclinical studies demonstrate that repeated D2 antagonist administration downregulates spontaneously active DA neurons by producing overexcitation-induced inactivation of firing (depolarization block). Animal models of schizophrenia based on the gestational...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2019.05.009
更新日期:2020-02-01 00:00:00
abstract::Due in part to their rich behavioral repertoire rats have been widely used in behavioral studies of drug abuse-related traits for decades. However, the mouse became the model of choice for researchers exploring the genetic underpinnings of addiction after the first mouse study was published demonstrating the capabilit...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2013.05.047
更新日期:2014-01-01 00:00:00
abstract::In the prostatic portion of rat vas deferens, the non-selective adenosine receptor agonist NECA (0.1-30 microM), but not the A(2A) agonist CGS 21680 (0.001-10 microM), caused a facilitation of electrically evoked noradrenaline release (up to 43 +/- 4%), when inhibitory adenosine A(1) receptors were blocked. NECA-elici...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2004.03.015
更新日期:2004-08-01 00:00:00
abstract::The responses of the guinea-pig ileum myenteric plexus-longitudinal muscle to the food, drug and cosmetic dye erythrosin B (FD & C Red No. 3) were examined in acetylcholine- and electrically-stimulated preparations. Erythrosin B (10(-6)-10(-4)) reduced the amplitude of the mechanical responses produced by both stimuli...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(83)90001-1
更新日期:1983-02-01 00:00:00
abstract::In vivo and in vitro studies suggest a crucial role for Sphingosine 1-phosphate (S1P) and its receptors in the development of the nervous system. Dihydrosphingosine 1-phosphate (dhS1P), a reduced form of S1P, is an agonist at S1P receptors, but the pharmacology and physiology of dhS1P has not been widely studied. The ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2011.10.005
更新日期:2012-02-01 00:00:00
abstract::The stable transcription factor ΔFosB is induced in the nucleus accumbens (NAc) by chronic exposure to several drugs of abuse, and transgenic expression of ΔFosB in the striatum enhances the rewarding properties of morphine and cocaine. However, the mechanistic basis for these observations is incompletely understood. ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2011.08.046
更新日期:2011-12-01 00:00:00
abstract::The purpose of this experiment was to study the electrophysiological interactions between phencyclidine and NMDA receptor agonists. Drugs were directly applied to cerebellar Purkinje neurons of urethane-anesthetized rats, through a multibarreled pipette by pressure ejection. Neuronal activity was recorded extracellula...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(91)90112-o
更新日期:1991-09-01 00:00:00
abstract::In rodents, insufficient adenosine produces behavioral and physiological symptoms consistent with several comorbidities of autism. In rodents and humans, stimuli postulated to increase adenosine can ameliorate these comorbidities. Because adenosine is a broad homeostatic regulator of cell function and nervous system a...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2012.08.013
更新日期:2013-05-01 00:00:00
abstract::Electrophysiology, immunostaining and time lapse imaging techniques were employed to study the mechanism of long-term depression (LTD) induced by DHPG, a specific group I metabotropic glutamate receptor (mGluR) agonist. Experiments were performed in primary hippocampal culture or in the CA1 area of acute rat hippocamp...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(01)00134-4
更新日期:2001-11-01 00:00:00
abstract::Receptor-mediated signal transduction is thought to play an important role in neuronal differentiation and the modification of synaptic connections during brain development. The intracellular signalling molecule phospholipase C-beta1 (PLC-beta1), which is activated via specific neurotransmitter receptors, has recently...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(98)00056-2
更新日期:1998-04-01 00:00:00
abstract::The aim of the present study was to evaluate, by means of quantitative and multivariate analyses, the effects of diazepam on the behavioral structure of the rat's response to pain in the hot-plate test as well as whether such changes are associated with drug-induced effects on anxiety and/or nociception. To this purpo...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2012.03.026
更新日期:2012-08-01 00:00:00
abstract::A new in vivo pharmacological method for the quantitative evaluation of alpha 1-adrenoceptor agonists and antagonists has been developed. It consists of recording the myoclonic twitch activity (MTA) of the suprahyoideal muscle of rats anesthetized with urethane. In these animals, the isomers of amphetamine elicited my...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(86)90175-9
更新日期:1986-05-01 00:00:00
abstract::Behavioural studies can help to validate, modify and refine schemes for classifying receptors that are developed from electrophysiological and biochemical experiments. Drug discrimination constitutes one family of behavioural techniques that is being extensively used for studying subtypes of receptors, mainly because ...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/0028-3908(87)90064-5
更新日期:1987-07-01 00:00:00
abstract::Bradykinin interacts with the bradykinin B2 receptor on dorsal root ganglion (DRG) neurons, setting off a series of reactions inside the cells that ultimately make the vanilloid receptor 1 more sensitive to a normal stimulus by activating various enzymes coupled with second messenger signaling cascades. Zaltoprofen, a...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2005.01.011
更新日期:2005-06-01 00:00:00
abstract::Amphetamine-type stimulants (ATS) are the second most consumed illicit drug worldwide and lack good treatments for associated substance use disorders, lagging behind other addictive drugs. For this reason, a deeper understanding of the pharmacodynamics of ATS is required. The present study seeks to determine amphetami...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2018.10.032
更新日期:2019-01-01 00:00:00
abstract::The effect of acute exposure to alcohols on ion current mediated by recombinant 5-HT3RA receptors transiently expressed in human embryonic kidney 293 cells was investigated. Cells transfected with 5-HT3RA cDNA expressed receptors with pharmacological and functional properties similar to those of native 5-HT3 receptors...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(94)90131-7
更新日期:1994-12-01 00:00:00
abstract::The elevation of extracellular 5-HT after systemic administration of 5-HT reuptake inhibiting drugs is strongly potentiated by agents capable of blocking 5-HT1A autoreceptors in the midbrain raphe. The present in vivo microdialysis study was aimed at assessing the relative importance of 5-HT reuptake inhibition versus...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(97)00050-6
更新日期:1997-04-01 00:00:00
abstract::Slow excitatory postsynaptic currents (EPSCs) mediated by metabotropic glutamate receptors (mGlu receptors) have been reported in several neuronal subtypes, but their presence in hippocampal pyramidal neurons remains elusive. Here we find that in CA1 pyramidal neurons a slow EPSC is induced by repetitive stimulation w...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2016.08.028
更新日期:2017-03-15 00:00:00
abstract::Cocaine produces a motor-stimulant response in part by its actions within the mesolimbic dopamine system. Repeated exposure to cocaine induces an augmented motor activity response which is termed behavioral sensitization, or reverse tolerance. Previous studies have suggested that sensitization may result from increase...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(93)90023-v
更新日期:1993-12-01 00:00:00
abstract::(+)-2-Methyl-4-carboxyphenylglycine (LY367385), a potent and selective antagonist of mGlu1a metabotropic glutamate receptors, was neuroprotective in the following in vitro and in vivo models of excitotoxic death: (i) mixed cultures of murine cortical cells transiently exposed to N-methyl-D-aspartate (NMDA); (ii) rats ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(98)00159-2
更新日期:1999-02-01 00:00:00
abstract::The so-called generalized polarization (GP) of the fluorescent probe Laurdan and the steady-state fluorescence anisotropy of the probe diphenylhexatriene (DPH) and its phenylpropionic derivative (PA-DPH) were used to study the effects of several organochlorine insecticides of the chlorophenylethane, chlorinated cycloh...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(99)00194-x
更新日期:2000-04-03 00:00:00
abstract::In the human genome, 22 genes are coding for the class C G protein-coupled receptors that are receptors for the two main neurotransmitters glutamate and γ-aminobutyric acid, for Ca(2+) and for sweet and amino acid taste compounds. In addition to the GPCR heptahelical transmembrane domain responsible for G-protein acti...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2010.08.009
更新日期:2011-01-01 00:00:00
abstract::The effect of acute or repeated treatment with the antidepressant clomipramine (CIM) on N-methyl-D-aspartate (NMDA) evoked changes in extracellular 5-hydroxytryptamine (5-HT) in the raphe nuclei and frontal cortex of the same rat has been studied using microdialysis. Acute injection of CIM (10 or 20 mg/kg) caused an i...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(01)00078-8
更新日期:2001-09-01 00:00:00
abstract::Vesicular glutamate transporter 2 (VGLUT2)-which uptakes glutamate into presynaptic vesicles-is a fundamental component of the glutamate neurotransmitter system. Although several lines of evidence from genetically modified mice suggest a possible association of VGLUT2 with neuropathic pain, the specific role of VGLUT2...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2019.107869
更新日期:2020-03-01 00:00:00
abstract::Long-term memory formation requires the coordinated regulation of gene expression. Until recently nucleosome remodeling, one of the major epigenetic mechanisms for controlling gene expression, had been largely unexplored in the field of neuroscience. Nucleosome remodeling is carried out by chromatin remodeling complex...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2013.10.002
更新日期:2014-05-01 00:00:00
abstract::The bed nucleus of the stria terminalis (BNST) is a forebrain structure implicated in physiological and behavioral responses to emotional stress. However, the local neurochemical mechanisms mediating the BNST control of stress responses are not fully known. Here, we investigated the involvement of BNST cholinergic neu...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2015.10.018
更新日期:2016-02-01 00:00:00
abstract::We have previously demonstrated that an acute dose of Δ9-tetrahydrocanninbinol (THC), administered prior to extinction learning, facilitates later recall of extinction learning and modulates the underlying neural circuitry, including the ventromedial prefrontal cortex (vmPFC), hippocampus (HPC), and amygdala (AMYG). I...
journal_title:Neuropharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.neuropharm.2018.10.002
更新日期:2018-12-01 00:00:00
abstract::The influence of naloxone (a narcotic antagonist), bicuculline (a GABA antagonist), phentolamine (an alpha-blocking agent), propranolol (a beta-adrenergic blocking agent), haloperidol (a dopaminergic blocking agent), methysergide (a serotonergic blocking agent) and atropine (a muscarinic blocking agent), on the antino...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(84)90143-6
更新日期:1984-06-01 00:00:00
abstract::The alpha7 and alpha4beta2 nicotinic acetylcholine receptor (nAchR) subtypes have been shown to be involved in memory. It is also known that losses of frontal cortical nAchRs are correlated to declining memory function in Alzheimer's disease, but the subtype-specific role of frontal cortical nAchRs in memory has not b...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2007.03.008
更新日期:2007-06-01 00:00:00