Abstract：
:Metabotropic glutamate receptor subtype 5 (mGluR5), encoded by the GRM5 gene, represents a compelling novel drug target for the treatment of schizophrenia. mGluR5 is a postsynaptic G-protein coupled glutamate receptor strongly linked with several critical cellular processes that are reported to be disrupted in schizophrenia. Accordingly, mGluR5 positive allosteric modulators show encouraging therapeutic potential in preclinical schizophrenia models, particularly for the treatment of cognitive dysfunctions against which currently available therapeutics are largely ineffective. More work is required to support the progression of mGluR5-targeting drugs into the clinic for schizophrenia treatment, although some obstacles may be overcome by comprehensively understanding how mGluR5 itself is involved in the neurobiology of the disorder. Several processes that are necessary for the regulation of mGluR5 activity have been identified, but not examined, in the context of schizophrenia. These processes include protein-protein interactions, dimerisation, subcellular trafficking, the impact of genetic variability or mutations on protein function, as well as epigenetic, post-transcriptional and post-translational processes. It is essential to understand these aspects of mGluR5 to determine whether they are affected in schizophrenia pathology, and to assess the consequences of mGluR5 dysfunction for the future use of mGluR5-based drugs. Here, we summarise the known processes that regulate mGluR5 and those that have already been studied in schizophrenia, and discuss the consequences of this dysregulation for current mGluR5 pharmacological strategies. This article is part of the Special Issue entitled 'Metabotropic Glutamate Receptors, 5 years on'.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Matosin N,Fernandez-Enright F,Lum JS,Newell KAdoi
10.1016/j.neuropharm.2015.08.003subject
Has Abstractpub_date
2017-03-15 00:00:00pages
73-91eissn
0028-3908issn
1873-7064pii
S0028-3908(15)30049-6journal_volume
115pub_type
杂志文章,评审abstract：:Brain inosine and hypoxanthine were measured in mice at intervals following the intraperitoneal injection of pentylenetetrazol (PTZ), 100 mg/kg. These purines increased only after myoclonic jerks appeared and were maximal at the time of tonic hindlimb extension. Phenytoin and phenobarbital, which prevent tonic hindlim...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(83)90161-2
更新日期：1983-05-01 00:00:00
abstract：:Ginsenoside Rg1 (Rg1) is a major bioactive ingredient in Panax ginseng that has low toxicity and has been shown to have neuroprotective effects. The objectives of the present study were to explore the potential of the application of Rg1 for the treatment of Parkinson's disease (PD) and to determine whether its neuropr...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2015.10.024
更新日期：2016-02-01 00:00:00
abstract：:Chloralose-anesthetized rats, spinalized at C1, were used to investigate the effects of spinal infusion of dopamine on renal sympathetic nerve activity (RSNA). A subarachnoid spinal superfusion technique was used to localize dopamine in the spinal cord while renal sympathetic nerve activity was recorded from the left ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(83)90242-3
更新日期：1983-03-01 00:00:00
abstract：:The obesity epidemic is one of the biggest health challenges globally and rates have tripled since 1975. Overeating is the largest determinant of obesity, yet little is understood of the neural mechanisms underlying why individuals consume food regardless of satiety. The lateral hypothalamic (LH) input to the ventral ...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2019.05.014
更新日期：2019-08-01 00:00:00
abstract：:The efficacy of antidepressant drugs with serotonergic, noradrenergic, or dual reuptake inhibition was evaluated in reversing carrageenan-induced thermal hyperalgesia and mechanical allodynia in rats. Duloxetine (1-30mg/kg, i.p.), a balanced serotonergic-noradrenergic reuptake inhibitor (SNRI), was equiefficacious and...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2006.08.005
更新日期：2006-12-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(97)00048-8
更新日期：1997-04-01 00:00:00
abstract：:The content of authentic 3H-spiroperidol and of its metabolites was measured in brain regions of rat, guinea pig and mouse receiving tracer doses of 3H-spiroperidol intravenously (0.2 to 0.5 micrograms/kg). The time course of the 3H-spiroperidol content of various brain regions shows that a steady state was maintained...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(83)90105-3
更新日期：1983-06-01 00:00:00
abstract：:Neural sensorimotor gating mechanisms prevent the interruption of ongoing information processing routines by ensuing stimuli to permit mental integration and adaptive behavior. Prepulse inhibition (PPI), an operational measure of sensorimotor gating, is now being investigated using murine models to exploit transgenic ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(00)00030-7
更新日期：2000-08-23 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
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.06.014
更新日期：2018-08-01 00:00:00
abstract：:Disruptions in synaptic plasticity in the dorsal striatum may contribute to the pathophysiology underlying Parkinson's disease. Here we report a novel, chemically-induced form of plasticity induced by application of the potassium channel blocker tetraethylammonium (TEA) in the dorsolateral striatum of the adult rat. T...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2004.09.018
更新日期：2005-02-01 00:00:00
abstract：:Simultaneous recordings of responses of substantia gelatinosa and deep dorsal horn neurones to thermal noxious cutaneous stimulation were made in spinalized cats anaesthetized with urethane/chloralose. Morphine, whether applied iontophoretically in the substantia gelatinosa (50-200 nA) or injected intravenously (1.0-1...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(83)90270-8
更新日期：1983-01-01 00:00:00
abstract：:Biochemical, behavioral and electrophysiological evidence suggests interactions between pathways containing neuronal nicotinic acetylcholine receptors (NAChRs) and excitatory amino acid receptors. Recently, protective effects of nicotine against N-methyl-D-aspartate (NMDA)-induced toxicity in primary cortical cultures...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(96)00162-1
更新日期：1997-01-01 00:00:00
abstract：BACKGROUND:Nucleus accumbens (NAc) and prefrontal cortex (PFC) dopaminergic and glutamatergic systems are involved in fear/anxiety-related behaviors; meanwhile NAc dopaminergic system activity is mediated by PFC via NAc glutamatergic projections. This study has investigated the involvement of NAc shell dopaminergic sys...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2013.03.017
更新日期：2013-08-01 00:00:00
abstract：:The kinetics of synaptic currents is largely determined by the postsynaptic receptor gating and the concentration time course of synaptic neurotransmitter. While the analysis of current responses to rapid agonist application provides the means to study the ligand-gated receptor gating, no direct tools are available to...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2004.07.003
更新日期：2004-12-01 00:00:00
abstract：:In this study, we analysed the implication of superoxide (O2-.) and nitric oxide (NO.) free radicals and their resulting product peroxynitrite (ONOO-) in the neuronal death induced by the activation of the glutamatergic receptor of the N-methyl-D-aspartate (NMDA) subtype using cultured cerebellar granule cells. The NO...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(93)90020-4
更新日期：1993-11-01 00:00:00
abstract：:The possible synergism between caffeine and muscarinic antagonists to inhibit haloperidol-induced catalepsy was investigated with the bar test in rats. Pretreatment with low doses of caffeine (1-3 mg/kg), a non-selective adenosine antagonist, dose dependently reduced the intensity and increased the onset latency of ca...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(03)00202-8
更新日期：2003-09-01 00:00:00
abstract：:A study has been undertaken to identify the category of receptors mediating the inhibitory effects of adenosine on evoked activity in slices of olfactory cortex in the rat. The approach has been to measure the relative potencies of adenosine and a range of structural analogues [2-chloroadenosine, 2' deoxyadenosine, cy...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(85)90195-9
更新日期：1985-11-01 00:00:00
abstract：:Tobacco addiction is highly co-morbid with a variety of mental health conditions, including schizophrenia, mood and anxiety disorders. Nicotine, the primary psychoactive compound in tobacco-related products is known to functionally modulate brain circuits that are disturbed in these disorders. Nicotine can potently re...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2020.108411
更新日期：2021-02-15 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2019.04.029
更新日期：2019-12-15 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2016.04.009
更新日期：2017-02-01 00:00:00
abstract：:Extrapyramidal syndromes (EPS) caused by antipsychotic therapy are currently treated with anticholinergics that lack selectivity for the five muscarinic receptor subtypes. Since these receptors are heterogeneously expressed among the different classes of striatal neurons and their afferents, it can be expected that th...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2014.02.005
更新日期：2014-06-01 00:00:00
abstract：OBJECTIVES:To explore the role of 5' adenosine monophosphate-activated protein kinase/sirtuin1-sirtuin3 (AMPK/SIRT1-SIRT3) signaling pathway in behavioral and neuroinflammation/oxidative stress alterations in unpredictable chronic mild stress (UCMS) model mice. METHODS:Male ICR mice weighing 20-22 g were used in this ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2019.107925
更新日期：2020-03-15 00:00:00
abstract：:The effects of pretreatment of rats with an intrahypothalamic injection of 6-hydroxydopamine on the thermal responses induced by intrahypothalamic injection of noradrenaline, prostaglandin E2, thyrotropin-releasing hormone or beta-endorphin were assessed. Administration of either noradrenaline (2-10 micrograms), prost...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(85)90188-1
更新日期：1985-11-01 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
abstract：:The N-methyl-D-aspartate (NMDA) antagonist ifenprodil and several structurally related compounds are highly selective for the NR2B-containing receptor subtype. This selectivity could provide an explanation for the reported difference of the analgesic and side-effect profile of ifenprodil-like compounds from other NMDA...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(00)00148-9
更新日期：2001-01-01 00:00:00
abstract：:The intravenous administration of L-5-hydroxytryptophan (5-HTP), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), p-chloroamphetamine (PCA), LSD and methysergide to acute spinal rats, transected at C1, stimulated the flexor reflexes induced by electrical stimulation applied to the skin of the toe. The enhancement produced...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(87)90101-8
更新日期：1987-09-01 00:00:00
abstract：:To compare the actions of prototypic drugs which are selective for phencyclidine and sigma receptors, the electrophysiological effects of phencyclidine (PCP),3-[3-hydroxyphenyl]-N-(1-propyl)piperidine [+)3-PPP), and 1,3-di(2-tolyl)guanidine (DTG) on CA1 hippocampal pyramidal neurons were examined. A wide range of conc...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(88)90012-3
更新日期：1988-11-01 00:00:00
abstract：:Binge alcohol (ethanol) drinking is associated with profound adverse effects on our health and society. Rimonabant (SR141716A), a CB1 receptor inverse agonist, was previously shown to be effective for nicotine cessation and obesity. However, studies using rimonabant were discontinued as it was associated with an incre...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2017.10.040
更新日期：2018-03-15 00:00:00
abstract：:GABAA and glycine receptors are close relatives in the "gene superfamily" of ligand-gated ion channels, but have distinctly different pharmacology. For example, barbiturates have two effects on GABAA receptors (GABAA-R): at low micromolar concentrations (2-5 microM), the anesthetic barbiturate methohexital potentiates...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(96)00088-3
更新日期：1996-01-01 00:00:00
