Abstract:
:Absence epilepsy is generated by the cortico-thalamo-cortical network, which undergoes a finely tuned regulation by metabotropic glutamate (mGlu) receptors. We have shown previously that potentiation of mGlu1 receptors reduces spontaneous occurring spike and wave discharges (SWDs) in the WAG/Rij rat model of absence epilepsy, whereas activation of mGlu2/3 and mGlu4 receptors produces the opposite effect. Here, we have extended the study to mGlu5 receptors, which are known to be highly expressed within the cortico-thalamo-cortical network. We used presymptomatic and symptomatic WAG/Rij rats and aged-matched ACI rats. WAG/Rij rats showed a reduction in the mGlu5 receptor protein levels and in the mGlu5-receptor mediated stimulation of polyphosphoinositide hydrolysis in the ventrobasal thalamus, whereas the expression of mGlu5 receptors was increased in the somatosensory cortex. Interestingly, these changes preceded the onset of the epileptic phenotype, being already visible in pre-symptomatic WAG/Rij rats. SWDs in symptomatic WAG/Rij rats were not influenced by pharmacological blockade of mGlu5 receptors with MTEP (10 or 30 mg/kg, i.p.), but were significantly decreased by mGlu5 receptor potentiation with the novel enhancer, VU0360172 (3 or 10 mg/kg, s.c.), without affecting motor behaviour. The effect of VU0360172 was prevented by co-treatment with MTEP. These findings suggest that changes in mGlu5 receptors might lie at the core of the absence-seizure prone phenotype of WAG/Rij rats, and that mGlu5 receptor enhancers are potential candidates to the treatment of absence epilepsy. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
D'Amore V,Santolini I,van Rijn CM,Biagioni F,Molinaro G,Prete A,Conn PJ,Lindsley CW,Zhou Y,Vinson PN,Rodriguez AL,Jones CK,Stauffer SR,Nicoletti F,van Luijtelaar G,Ngomba RTdoi
10.1016/j.neuropharm.2012.05.044subject
Has Abstractpub_date
2013-03-01 00:00:00pages
330-8eissn
0028-3908issn
1873-7064pii
S0028-3908(12)00252-3journal_volume
66pub_type
杂志文章abstract::The effects of several stress procedures on the release of 5-HT in the dorsal and median raphe nuclei (DRN and MRN, respectively) and in forebrain structures of the rat brain innervated by both nuclei have been studied using intracerebral microdialysis. Handling for 30 sec, a saline injection and forced swimming for 5...
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::Behavioral sensitization, or augmented locomotor response to successive drug exposures, results from neuroadaptive changes contributing to addiction. Both the medial prefrontal cortex (mPFC) and ventral tegmental area (VTA) influence behavioral sensitization and display increased immediate-early gene and BDNF expressi...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2011.04.026
更新日期:2011-09-01 00:00:00
abstract::Peristaltic reflex activity in the guinea-pig isolated ileum was elicited by slow intraluminal infusion of Tyrode solution. The reflex was abolished by the ganglionic blocking drug hexamethonium. However, in more than half of the preparations, the peristaltic reflex was restored by the opioid antagonist naloxone. Hexa...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(87)90018-9
更新日期:1987-11-01 00:00:00
abstract::The aim of this study was to examine the role of GABAergic neurotransmission in amygdala nuclei in low- (LR) and high-anxiety (HR) rats after repeated corticosterone administration and acute injection of the benzodiazepine midazolam. The animals were divided into LR and HR groups based on the duration of their conditi...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2015.08.039
更新日期:2015-12-01 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::Dopamine denervation in Parkinson's disease and repeated Levodopa (L-DOPA) administration that induces dyskinesias are associated with an enhancement of basal ganglia neuropeptide transmission. Various adjunct non-dopaminergic treatments to Levodopa were shown to reduce and/or prevent dyskinesias. The aim of this stud...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2009.06.030
更新日期:2010-01-01 00:00:00
abstract::In this study we investigate the presence, modulation and biological function of P2 receptors and extracellular ATP in cultured cerebellar granule neurons. As we demonstrate by RT-PCR and western blotting, both P2X and P2Y receptor subtypes are expressed and furthermore regulated as a function of neuronal maturation. ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(01)00197-6
更新日期:2002-03-01 00:00:00
abstract::Compound IG20 is a newly synthesised sulphated glycolipid that promotes neuritic outgrowth and myelinisation, at the time it causes the inhibition of glial proliferation and facilitates exocytosis in chromaffin cells. Here we have shown that IG20 at 0.3-10 μM afforded neuroprotection in rat hippocampal slices stressed...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2016.12.016
更新日期:2017-04-01 00:00:00
abstract::Dopamine (DA) is a classical neurotransmitter modulating various brain functions by acting on its specific receptors. In addition, DA is a reactive molecule that has been implicated in neurodegeneration, especially in Parkinson's disease. Here we show that DA inhibited cell growth of dopamine transporter transfected c...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2004.11.013
更新日期:2005-03-01 00:00:00
abstract::Serotonin (5-HT) modulates the hypothalamic-pituitary-adrenal (HPA) axis response to stress. We examined the effect of chronic restraint stress (CRS; 20 min/day) as compared to control (CTRL) conditions for 14 days, on: 1) restraint-induced ACTH and corticosterone (CORT) secretion in rats pretreated with vehicle or SB...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2013.03.013
更新日期:2013-08-01 00:00:00
abstract::Parkinson's disease (PD) shows a complex etiology, where both genetic and environmental factors contribute to initiation and advance of pathology. Mitochondrial dysfunction and mutation of genes implicated in mitochondria quality control are recognized contributors to etiopathology and progression of PD. Here we repor...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2013.10.009
更新日期:2014-02-01 00:00:00
abstract::The influence of the subunit composition of human GABA(A) receptors upon the GABA-modulatory properties of 5alpha-pregnan-3alpha-ol-20-one (5alpha,3alpha) has been examined using the Xenopus laevis oocyte expression system and the two electrode voltage-clamp technique. Steroid potency (EC(50)) is modestly influenced b...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(02)00172-7
更新日期:2002-09-01 00:00:00
abstract::Diazepam binding inhibitor (DBI) acts in brain by binding to GABAA/benzodiazepine receptors (GBR) and to mitochondrial benzodiazepine receptors (MBR). Because DBI acting at MBR, has been shown to be an effector of ACTH-induced steroidogenesis and stress is known to change the level of GBR and MBR, the model of acute n...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(11)80015-8
更新日期:1991-12-01 00:00:00
abstract::Clinically effective antidepressants are thought to exert their therapeutic effects by facilitating central monoamine neurotransmission. However, recent data showing that neurokinin-1 receptor (NK1R) antagonists have antidepressant properties in both animal and clinical studies raise the possibility that classical ant...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2004.02.013
更新日期:2004-06-01 00:00:00
abstract::Many studies have described potent effects of BDNF, 17β-estradiol or androgen on hippocampal synapses and their plasticity. Far less information is available about the interactions between 17β-estradiol and BDNF in hippocampus, or interactions between androgen and BDNF in hippocampus. Here we review the regulation of ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2013.04.029
更新日期:2014-01-01 00:00:00
abstract::Pretreatment of primary cultures of cerebellar granule cells with sodium nitroprusside (SNP) protected these neurons from delayed death induced by glutamate and N-methyl-D-aspartate (NMDA). This neuroprotective effect was not mimicked by S-nitroso-N-acetylpenicillamine (SNAP) which like SNP stimulates guanylate cyclas...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(91)90171-7
更新日期:1991-11-01 00:00:00
abstract::Endocannabinoids are suggested to control pain, even though their clinical use is not fully validated and the underlying mechanisms are incompletely understood. To clarify the targets of endocannabinoid actions, we studied how activation of the endocannabinoid CB1 receptor (CB1R) affects neuronal responses in two in v...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2017.12.013
更新日期:2018-03-15 00:00:00
abstract::The cannabinoid receptor CB2 plays a significant role in the regulation of immune function whereas neuronal expression remains a subject of contention. Multiple studies have described CB2 in retina and a recent study showed that CB2 deletion altered retinal visual processing. We revisited CB2 expression using immunohi...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2018.08.007
更新日期:2018-10-01 00:00:00
abstract::Acetylcholine-induced currents were measured in partially depolarized mouse soleus muscles, denervated for 3-6 days by using a point voltage clamp. When 0.25 microM d-tubocurarine (d-Tc) was used, the weak currents provoked by 0.1 microM ACh, at a holding potential of -20 mV, were barely affected, while the large curr...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(90)90070-8
更新日期:1990-06-01 00:00:00
abstract::In the present study we examined the effect of MPEP [2-methyl-6-(phenylethynyl)-pyridine] a potent, selective and systemically active metabotropic glutamate receptor (mGluR) type I (subtype mGluR5) antagonist on conditioned morphine reward in mice. In an unbiased version of conditioned place preference (CPP) paradigm,...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(02)00309-x
更新日期:2002-12-01 00:00:00
abstract::3,4-Methlylenedioxymethamphetamine (MDMA) administration (4 x 15 mg/kg) on a single day has been shown to cause path integration deficits in rats. While most animal experiments focus on single binge-type models of MDMA use, many MDMA users take the drug on a recurring basis. The purpose of this study was to compare th...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2008.07.006
更新日期:2008-12-01 00:00:00
abstract::The 15q25 gene cluster contains genes that code for the α5, α3, and β4 nicotinic acetylcholine receptor (nAChRs) subunits, and in human genetic studies, has shown the most robust association with smoking behavior and nicotine dependence to date. The limited available animal studies implicate a role for the α5 and β4 n...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2013.01.017
更新日期:2013-07-01 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 incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) are growth factors that have shown neuroprotective effects in animal models of Parkinson's and Alzheimer's disease. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2017.02.013
更新日期:2017-05-01 00:00:00
abstract::Efflux of exogenous [3H]taurine from superfused slices of cerebral cortex of rat was enhanced by the calcium chelators EDTA and EGTA and by large concentrations of unlabelled taurine and histidine. The enhancement by EDTA and EGTA could be totally blocked by excess calcium, but that by the amino acids only partially. ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(84)90202-8
更新日期:1984-03-01 00:00:00
abstract::The effect of clonidine (0.1 mg/kg, i.p.), as a three-injection course, on behaviour in the forced swimming test was studied in rats injected intracerebroventricularly (i.c.v.) with 150 micrograms 5,7-dihydroxy-tryptamine (5,7-DHT) to destroy serotonin (5-HT) neurones or treated with 100 mg/kg (i.p.) (+/-)-sulpiride o...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(92)90064-v
更新日期:1992-04-01 00:00:00
abstract::Antidepressants up-regulate the cAMP response element binding protein (CREB) and the brain-derived neurotrophic factor (BDNF) in hippocampus and these effects contribute to the protection of hippocampal neurons from stressful stimuli such as high glucocorticoid levels. CREB can be activated by both protein kinase A an...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2004.07.035
更新日期:2004-12-01 00:00:00
abstract::The presence of ethanol, 100 microM, in the superfusate enhanced the spontaneous release of previously uptaken [3H]-dopamine from slices of rat corpus striatum, but produced a small inhibition of K+-stimulated release. The concomitant presence of picrotoxin, 10 microM, in the superfusate prevented the enhancement of s...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(83)90234-4
更新日期:1983-12-01 00:00:00
abstract::The metabotropic glutamate receptor 2 (mGlu2) plays an important role in the presynaptic control of glutamate release and several mGlu2 positive allosteric modulators (PAMs) have been under assessment for their potential as antipsychotics. The binding mode of mGlu2 PAMs is better characterized in functional terms whil...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2016.08.040
更新日期:2017-03-15 00:00:00
abstract::Anti-emetic drugs such as the tachykinin NK(1) receptor antagonists are useful to control emesis induced by diverse challenges. Evidence suggests pungent capsaicin-like TRPV1 activators also have broad inhibitory anti-emetic activity. However, pungent compounds are associated with undesirable effects including adverse...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2009.10.002
更新日期:2010-02-01 00:00:00