Abstract:
:Group II metabotropic glutamate (mGlu) receptor agonists were efficacious in randomized clinical research trials for schizophrenia and generalized anxiety disorder. The regional quantification of mGlu(2) and mGlu(3) receptors remains unknown. A selective and structurally novel mGlu(2/3) receptor agonist, 2-amino-4-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY459477) was tritiated and the distribution of mGlu(2) and mGlu(3) receptors was studied in transgenic mice lacking either mGlu(2), mGlu(3) or both receptors. LY459477 is an agonist with 1-2 nM potency for rodent and human mGlu(2) and mGlu(3) receptors. The functional selectivity of LY459477 was demonstrated by over 640-fold selectivity and the displacement binding selectivity was greater than 320-fold for all glutamate receptors except mGlu(6) (∼230-fold). More than 1000-fold selectivity was demonstrated for all non-glutamate receptors known to be targeted by antipsychotic drugs. Like atypical antipsychotic drugs, LY459477 reversed in vitro electrophysiological effects of a serotonergic hallucinogen and behavioral effects of phencyclidine or amphetamine. There was virtually no binding of [(3)H]LY459477 to any brain region in mice with a deletion of both mGlu(2) and mGlu(3) receptors. Regions enriched in mGlu(2) receptors included the medial prefrontal cortex, select hippocampal regions, the medial mammillary nucleus, the medial habenula, and the cerebellar granular cell layer. Regions enriched in mGlu(3) receptors were the dorsolateral entorhinal cortex, the hippocampal CA1 field, the piriform cortex, the substantia nigra, the thalamic reticular nucleus, and primary sensory thalamic nuclei. These findings suggest [(3)H]LY459477 should be a useful tool to further define the role of mGlu(2) and mGlu(3) receptors throughout the brain with respect to major neuropsychiatric syndromes. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Wright RA,Johnson BG,Zhang C,Salhoff C,Kingston AE,Calligaro DO,Monn JA,Schoepp DD,Marek GJdoi
10.1016/j.neuropharm.2012.01.019subject
Has Abstractpub_date
2013-03-01 00:00:00pages
89-98eissn
0028-3908issn
1873-7064pii
S0028-3908(12)00039-1journal_volume
66pub_type
杂志文章abstract::Destruction of the ventral noradrenergic pathway elicited by administration of 6-hydroxydopamine (6-OHDA, 5 micrograms into each side of the ventral pons) reduced the content of norepinephrine (NE) in the anterior hypothalamus (-80%) and induced an increase in arterial blood pressure (ABP) and in heart rate. These hyp...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(83)90257-5
更新日期:1983-01-01 00:00:00
abstract::The excitatory amino acid antagonist, D-alpha-aminoadipate, was found to be a potent antagonist of responses to N-methyl-D-aspartate and L-aspartate, but less potent against L-glutamate responses of neurones in the rat caudal trigeminal nucleus. The responses to quisqualate and kainate were relatively unaffected by D-...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(82)90020-x
更新日期:1982-05-01 00:00:00
abstract::The neuronal nicotinic acetylcholine receptor alpha7 (nAChR alpha7) may be involved in cognitive deficits in Schizophrenia and Alzheimer's disease. A fast pharmacological characterization of homomeric alpha7 receptors is mostly hampered by their low functional expression levels in heterologous expression systems. In t...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2004.10.003
更新日期:2005-02-01 00:00:00
abstract::Paeoniflorin (PF) is a major bioactive ingredient in Radix Paeonia alba roots that has low toxicity and has been shown to have neuroprotective effects. Our in vitro experiments suggested that PF affords a significant neuroprotective effect against MPP+-induced damage and apoptosis in PC12 cells through Bcl-2/Bax/caspa...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2017.01.009
更新日期:2017-04-01 00:00:00
abstract::We examined the effects of two protein tyrosine phosphatase inhibitors on the induction of synaptic plasticity in CA1 slices of rat hippocampus. Field potential recordings were made in stratum radiatum in response to stimulation of the Schaffer collateral afferents. Bath application of the tyrosine phosphatase inhibit...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(00)00087-3
更新日期:2000-09-01 00:00:00
abstract::To study the effects of maternal alcohol ingestion on brain adenylate cyclase in offspring, rats were given ethanol in the drinking water before, during and after gestation. Fifteen-day-old pups from alcoholic mothers had reduced body and wet brain weight and protein content with normal concentrations of DNA and RNA i...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(83)90201-0
更新日期:1983-11-01 00:00:00
abstract::γ-Aminobutyric acid B (GABAB) receptors and their ligands are postulated as potential therapeutic targets for the treatment of several brain disorders, including drug dependence. Over the past fifteen years positive allosteric modulators (PAMs) have emerged that enhance the effects of GABA at GABAB receptors and which...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2014.06.016
更新日期:2015-01-01 00:00:00
abstract::The benzodiazepine--gamma-aminobutyric acid (GABA) receptor--ionophore system is an oligomeric complex, composed of at least three interacting components. These three components have been well characterized in vitro by radioreceptor binding assays. A variety of centrally acting anxiolytic, depressant, anticonvulsant a...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/0028-3908(83)90114-4
更新日期:1983-12-01 00:00:00
abstract::1-Methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine (2'-NH2-MPTP) causes long-term depletions in cortical and hippocampal serotonin (5-HT) and norepinephrine (NE) that are accompanied by acute elevations in glial fibrillary acidic protein (GFAP) and argyrophilia. To further investigate the hypothesis that these cha...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2005.09.006
更新日期:2006-03-01 00:00:00
abstract::Electrophysiological, biochemical, and behavioural studies have suggested that opiate withdrawal is mediated, at least in part, by a hyperactivity of locus coeruleus (LC) neurones. The aim of this study was to evaluate, using single-unit extracellular recordings, the role of NO in the opiate withdrawal-induced hyperac...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(98)00063-x
更新日期:1998-06-01 00:00:00
abstract::The effects of 5-hydroxytryptamine (5-HT) on neuronal excitability, evaluated as depolarization-induced firing rate, and on amino acid release, measured as electrically-evoked [(3)H]GABA and [(3)H]d-aspartate efflux, were investigated in rat primary cortical neuronal cultures. 5-HT displayed a concentration-dependent,...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2006.10.017
更新日期:2007-03-01 00:00:00
abstract::Clinical neuropathologic studies suggest that the selective vulnerability of hippocampal CA1 pyramidal projection neurons plays a key role in the onset of cognitive impairment during the early phases of Alzheimer's disease (AD). Disruption of this neuronal population likely affects hippocampal pre- and postsynaptic ef...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2013.10.018
更新日期:2014-04-01 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::Sensory gating can be assessed in rodents and humans using an auditory conditioning (C)-test (T) paradigm, with schizophrenic patients exhibiting a loss of gating. Dysregulation of the endocannabinoid system has been proposed to be involved in the pathogenesis of schizophrenia. We studied auditory gating and the effec...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2008.08.039
更新日期:2008-12-01 00:00:00
abstract::Dopamine (DA) efflux from terminals of the mesocorticolimbic system is linked to incentive motivation, drug dependency and schizophrenia. Strategies for modulating dopaminergic activity have focused on transmitter receptors or the DA transporter, not on DA release, largely due to lack of systemically available drugs a...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2009.02.001
更新日期:2009-05-01 00:00:00
abstract::Dopamine (DA) is a major catecholamine neurotransmitter in the mammalian brain that controls neural circuits involved in the cognitive, emotional, and motor aspects of goal-directed behavior. Accordingly, perturbations in DA neurotransmission play a central role in several neuropsychiatric disorders. Somewhat surprisi...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2017.04.033
更新日期:2017-09-15 00:00:00
abstract::The effects of ruthenium red (RR) on transmitter release and pre-synaptic currents were studied in the mouse neuromuscular junction. The action of RR (10 microM) was shown not only in the complete suppression of nerve-evoked muscle contractions associated with the depression of endplate potential amplitude but also in...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(96)84632-6
更新日期:1996-05-01 00:00:00
abstract::Elimination of brain cholesterol occurs in the form of 24S-hydroxycholesterol (24S-HCh) that may modulate physiological processes outside the brain. Here, using microelectrode recording of postsynaptic responses (end-plate potentials, EPPs) and fluorescent marker (FM1-43) for endo-exocytosis we studied the effects of ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2019.03.018
更新日期:2019-05-15 00:00:00
abstract::The role of neurally born acetylcholine in the central modulation of cardiovascular short-term variability was assessed using a pharmacological probe physostigmine, a cholinesterase inhibitor that can act centrally also. Experiments were performed in instrumented conscious rats. Equidistant sampling at 20 Hz of systol...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2005.12.009
更新日期:2006-06-01 00:00:00
abstract::N-methyl-D-aspartate (NMDA) receptors play several essential roles in the physiology and pathophysiology of the brain. Their activation results in long-term changes in glutamatergic synaptic transmission in several brain areas, but excessive activation of these receptors induces neurotoxicity. Some of NMDA-mediated ac...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2006.03.025
更新日期:2006-08-01 00:00:00
abstract::These experiments examined the effects of lithium and imipramine on the regulation by norepinephrine in vivo of (Na+, K+)-ATPase in brain and heart. The binding of ouabain and the activity of K+-phosphatase were used as indices of (Na+, K+)-ATPase. In the cerebral cortex, imipramine prevented, and lithium reduced, the...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(88)90042-1
更新日期:1988-03-01 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 effects of chronic administration of the nonselective monoamine oxidase (MAO) inhibitor, phenelzine, and two selective inhibitors, clorgyline, and pargyline on adrenergic receptor binding and MAO activity were studied in the rat brain. Chronic but not acute administration of both phenelzine and the MAO-A inhibitor...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(82)90091-0
更新日期:1982-04-01 00:00:00
abstract::We studied the effect of YM-39558, orotic acid ethylester, in a focal cerebral ischemia model in anesthetized cats. YM-39558 has good permeability across the blood brain barrier, and in the brain is hydrolyzed to orotic acid, the main active substance. Cats were subjected to permanent occlusion of the middle cerebral ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(98)00008-2
更新日期:1998-01-01 00:00:00
abstract::Clinical studies have shown that the major psychoactive ingredient of Cannabis sativa Δ9-tetrahydrocannabinol (THC) has some analgesic efficacy in neuropathic pain states. However, THC has a significant side effect profile. We examined whether the profile of THC could be improved by co-administering it with the first-...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2018.10.006
更新日期:2019-01-01 00:00:00
abstract::1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), or 0.9% saline, was administered to a group of common marmosets initially treated with the toxin 12-18 months previously. Initial treatment had consisted of a cumulative dose of 6-22 mg/kg (i.p.) which caused marked parkinsonism. Subsequently, the animals gradually ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(89)90122-6
更新日期:1989-10-01 00:00:00
abstract::Dopamine (DA) neurotransmission, particularly the ventral tegmental area-nucleus accumbens (VTA-NAcc) projection, underlies reward and aversion processing, and deficient DA function could underlie motivational impairments in psychiatric disorders. 6-hydroxydopamine (6-OHDA) injection is an established method for chron...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2016.03.048
更新日期:2016-10-01 00:00:00
abstract::The medullary dorsal horn (MDH or Sp5c/C1 region) plays a key role modulating the nociceptive input arriving from craniofacial structures. Some reports suggest that oxytocin could play a role modulating the nociceptive input at the MDH level, but no study has properly tested this hypothesis. Using an electrophysiologi...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2017.11.031
更新日期:2018-02-01 00:00:00
abstract::Recent observations from synaptosome preparations have questioned the tetrodotoxin (TTX) insensitivity of nicotine-evoked release in the striatum, a characteristic previously considered diagnostic of presynaptically located nicotinic acetylcholine receptors (nAChRs). Therefore, we have undertaken a comparison of nicot...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(96)00117-7
更新日期:1996-01-01 00:00:00
abstract::Dural plasma extravasation produced by electrical stimulation of the trigeminal ganglion was measured in rats and the concomitant expression of c-fos mRNA produced in the trigeminal nucleus caudalis (NtV) was measured using in situ hybridization techniques. The non-peptide NK1 receptor selective antagonist CP-99,994 (...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(94)00153-j
更新日期:1995-03-01 00:00:00