Abstract：
:The in vitro and in vivo properties of L-655,708, a compound with higher affinity for GABA(A) receptors containing an alpha5 compared to an alpha1, alpha2 or alpha3 subunit have been examined further. This compound has weak partial inverse agonist efficacy at each of the four subtypes but, and consistent with the binding data, has higher functional affinity for the alpha5 subtype. In a mouse hippocampal slice model, L-655,708 was able to enhance the long-term potentiation produced by a theta burst stimulation, consistent with a potential role for the alpha5 subtype in processes involving synaptic plasticity, such as learning and memory. When administered in a formulation specifically designed to achieve relatively constant plasma drug concentrations, and therefore maintain selective occupancy of alpha5- compared to alpha1-, alpha2- and alpha3-containing receptors (75+/-4% versus 22+/-10%, respectively), L-655,708 did not alter the dose of pentylenetetrazole required to induce seizures, indicating that the inverse agonist effects of L-655,708 at the alpha5 subtype are not associated with a proconvulsant liability. In the Morris water maze, L-655,708 enhanced performance not only during acquisition but also in a probe trial, demonstrating that this compound has cognition enhancing effects. These data further support the potential of alpha5-containing GABA(A) receptors as a target for novel cognition enhancing drugs.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Atack JR,Bayley PJ,Seabrook GR,Wafford KA,McKernan RM,Dawson GRdoi
10.1016/j.neuropharm.2006.04.018subject
Has Abstractpub_date
2006-11-01 00:00:00pages
1023-9issue
6eissn
0028-3908issn
1873-7064pii
S0028-3908(06)00124-9journal_volume
51pub_type
杂志文章abstract：:NMDA receptors (NMDAr) are widely expressed throughout the brain on many cell types, and loss of function of these receptors (ie: NMDAr hypofunction) is a candidate mechanism explaining working memory impairment in schizophrenia. However, the cellular source driving the working memory deficits caused by NMDAr hypofunc...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2020.108103
更新日期：2020-07-01 00:00:00
abstract：:A functional balance between excitatory and inhibitory control over dopamine (DA)-dependent behavioral and neurochemical effects of cocaine is afforded by the serotonin(2C) receptor (5-HT(2C)R) located within the ventral tegmental area and the nucleus accumbens (NAc). The 5-HT(2C)R located in the medial prefrontal cor...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2008.10.005
更新日期：2009-02-01 00:00:00
abstract：:The tryptophan metabolite kynurenic acid (KYNA) is an endogenous antagonist of the α7 nicotinic acetylcholine receptor (α7nAChR) and, at higher concentrations, inhibits ionotropic glutamate receptors. Increases in KYNA levels are seen in brain and cerebrospinal fluid in individuals with schizophrenia (SZ) and may be c...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2014.02.019
更新日期：2014-07-01 00:00:00
abstract：:More studies are required to develop therapeutic agents for treating spinocerebellar ataxia type 3 (SCA3), which is caused by mutant polyglutamine-expanded ataxin-3 and is the most prevalent subtype of spinocerebellar ataxias. T1-11 [N6-(4-Hydroxybenzyl) adenosine], isolated from a Chinese medicinal herb Gastordia ela...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2015.08.009
更新日期：2015-12-01 00:00:00
abstract：:Histamine is an aminergic neurotransmitter, which regulates wakefulness, arousal and attention in the central nervous system. Histamine receptors have been the target of efforts to develop pro-cognitive drugs to treat disorders such as Alzheimer's disease and schizophrenia. Cognitive functions including attention are ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2017.03.003
更新日期：2017-05-15 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：:We have used whole-cell patch clamp electrophysiology to characterise the actions of the P2 antagonist, cibacron blue, on the rat recombinant P2X4 receptor, stably expressed in human embryonic kidney 293 (HEK293) cells. In single cells, adenosine triphosphate (ATP) evoked inward currents, but the response was subject ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(98)00153-1
更新日期：1998-12-01 00:00:00
abstract：:Tau hyperphosphorylation and memory deficit are characteristic alterations of Alzheimer's disease (AD), and glycogen synthase kinase-3 (GSK-3) plays a crucial role in these AD-like changes. We have reported that activation of GSK-3 through ventricular injection of wortmannin and GF-109203X (WT/GFX, 100 microM each) in...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2007.02.008
更新日期：2007-06-01 00:00:00
abstract：:Family, twin and adoption studies demonstrate clearly that alcohol dependence and alcohol use disorders are phenotypically complex and heritable. The heritability of alcohol use disorders is estimated at approximately 50-60% of the total phenotypic variability. Vulnerability to alcohol use disorders can be due to mult...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2017.01.017
更新日期：2017-08-01 00:00:00
abstract：:SB-204269 (trans-(+)-6-acetyl-4S-(4-fluorobenzoylamino)-3, 4-dihydro-2,2-dimethyl-2H-benzo[b]pyran-3R-ol) shows anticonvulsant activity in a range of animal seizure models, with a high therapeutic index and a lack of side-effects. We have previously reported the characterisation of a novel binding site for [(3)H]-SB-2...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(00)00071-x
更新日期：2000-09-01 00:00:00
abstract：:Neural uptake of glutamate is executed by the structurally related members of the SLC1A family of solute transporters: GLAST/EAAT1, GLT-1/EAAT2, EAAC1/EAAT3, EAAT4, ASCT2. These plasma membrane proteins ensure supply of glutamate, aspartate and some neutral amino acids, including glutamine and cysteine, for synthetic,...
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
abstract：:The effect of in vivo administration of the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on striatal and extrastriatal D-1 and D-2 dopamine (DA) receptors was investigated in the rat. N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline treatment reduced specific [3H]SCH 23390 (7-chloro-8-hydroxy-2...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(94)90170-8
更新日期：1994-05-01 00:00:00
abstract：BACKGROUND:After neonatal ventral hippocampal lesions (NVHLs), adult rats exhibit evidence of neural processing deficits relevant to schizophrenia, including reduced prepulse inhibition (PPI) of acoustic startle and impaired sensory processing. In intact rats, the regulation of PPI by the ventral hippocampus (VH) is me...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2013.06.003
更新日期：2013-12-01 00:00:00
abstract：:The effects of intracerebroventricular (i.c.v.) administration of NT on the activity of midbrain DA neurons were studied in rats using single unit recording techniques. NT (i.c.v., 50 micrograms) was found to have no significant effect on the spontaneous activity of DA cells. On the other hand, NT treatment significan...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(90)90119-c
更新日期：1990-11-01 00:00:00
abstract：:Guinea-pigs, chronically exposed to simulated high altitude of 6000 m, showed alterations in some, but not all, neurotransmitter-receptor systems. Thus, peripheral (cardiac) beta-adrenergic receptors were decreased in numbers (Bmax) with an increased affinity although no alterations in endogenous cardiac norepinephrin...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(84)80013-1
更新日期：1984-02-01 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：:The effects of the novel antidepressant tianeptine on behaviours induced by the serotonin (5-HT) precursor 5-hydroxytryptophan (5-HTP) and the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) were investigated. Tianeptine (10 mg/kg, i.p.) significantly attenuated wet dog shakes (WDS) induced by 5-HTP...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(93)90138-s
更新日期：1993-09-01 00:00:00
abstract：:N-methyl-d-aspartate receptors (NMDARs) are profound regulators of glutamate neurotransmission and behavior. To coordinate components of the limbic system, the dorsal and ventral striatum integrate cognitive and emotional information towards the execution of complex behaviors. Striatal outflow is conveyed by medium sp...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.03.026
更新日期：2017-01-01 00:00:00
abstract：:This study confirms and extends an earlier report that acute administration of the serotonin (5-HT) antagonist, mianserin, caused a marked decrease in the density of 5-HT2 binding sites in brain of the rat (Blackshear and Sanders-Bush, 1982). Using [3H]ketanserin, a selective ligand for the 5-HT2 site, the present stu...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(86)90146-2
更新日期：1986-11-01 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 present studies examined the relationship between protein kinase C (PKC) and L-type voltage-dependent calcium channels in modulating the release of neurotransmitter from K(+)-depolarized rat spinal cord synaptosomes. Activators of PKC, such as phorbol 12-myristate 13-acetate (PMA), mezerein and oleoyl acetylglycer...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(92)90005-a
更新日期：1992-11-01 00:00:00
abstract：:Studies described here tested the hypothesis that phosphodiesterase 10A inhibition by a selective antagonist, MP-10, activates the dopamine D2 receptor expressing medium spiny neurons to a greater extent than the D1 receptor expressing neurons. We used regional pattern of c-Fos induction in the neostriatal subregions ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2015.08.008
更新日期：2015-12-01 00:00:00
abstract：:Quinine and quinidine are reported to potentiate the behavioural effects of serotonergic agents and monoamine uptake inhibitors. We have therefore investigated the presynaptic actions of quinine and quinidine on monoamine uptake and release in rat brain tissue in vitro. Quinidine evoked the release of [3H]5-HT, [3H]no...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(98)00075-6
更新日期：1998-07-01 00:00:00
abstract：:Downregulation of the astroglial glutamate transporter GLT-1 is observed in the nucleus accumbens (NAc) following administration of multiple drugs of abuse. The decrease in GLT-1 protein expression following cocaine self-administration is dependent on both the amount of cocaine self-administered and the length of with...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2017.09.019
更新日期：2018-01-01 00:00:00
abstract：:The voltage-dependent calcium channels (VDCCs) involved in K(+)-induced transmitter release have been studied. A maximally effective concentration of the N-type VDCC inhibitor, omega-conotoxin GVIA (GVIA) blocked the release of 5-HT (30%), DA (30%) and ACh (60%) but not that of GABA or glutamate. The O, P and Q-type V...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(96)00010-x
更新日期：1996-04-01 00:00:00
abstract：:One proposed factor contributing to the increased frequency of opioid overdose deaths is the emergence of novel synthetic opioids, including illicit fentanyl and fentanyl analogues. A treatment strategy currently under development to address the ongoing opioid crisis is immunopharmacotherapies or opioid-targeted vacci...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2019.107730
更新日期：2019-11-01 00:00:00
abstract：:Valid animal models of psychopathology need to include behavioural readouts informed by human findings. In the probabilistic reversal learning (PRL) task, human subjects are confronted with serial reversal of the contingency between two operant stimuli and reward/punishment and, superimposed on this, a low probability...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2012.07.025
更新日期：2012-11-01 00:00:00
abstract：:Depolarizations provoked by acetylcholine (ACh) and three dicholines, succinylcholine (SCh), glutarylcholine (GCh) and azelainylcholine (AzCh) were measured in normal and 3-7 days denervated muscles of adult, and in normal muscles of 0-27 days old mice and rats. Soleus and flexor digitorum superficialis muscles were m...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(89)90032-4
更新日期：1989-04-01 00:00:00
abstract：:Animal models of alcohol drinking and dependence are a critical resource for understanding the neurobiological mechanisms and development of more effective treatments for alcohol use disorder (AUD). Because most rat strains do not voluntarily consume large enough quantities of alcohol to adequately model heavy drinkin...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2020.108393
更新日期：2021-02-15 00:00:00
abstract：:Depotentiation, the reversal of long-term potentiation (LTP), can be induced by activation of metabotropic glutamate receptors (mGluRs) or NMDA receptors (NMDARs). Although NMDAR-dependent depotentiation is due to a protein phosphatase-dependent erasure of LTP, the notion that mGluR-dependent depotentiation also invol...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2005.01.008
更新日期：2005-06-01 00:00:00
