Abstract：
:A genetic component is associated with the development of many forms of epilepsy. Recently, mutations in the GABAA receptor have been linked to several inherited epilepsies. One of these mutations is a non-conservative change of alanine to aspartate in the third transmembrane domain of the alpha1 subunit. To determine the functional consequences of this alteration, mutated alpha subunits were transiently transfected along with wild-type beta3 and gamma2L subunits into HEK-293T cells. The mutated alpha1(A294D) subunit reduced GABA sensitivity of the receptor, increased the deactivation rate and slowed desensitization. The mutation caused a reduction in channel open time but no change in single channel conductance. Studies with additional mutants, altering the charge and/or size of the side-chain, indicated that both size and hydrophobicity of the residue at this location influence channel gating. The effects on GABA sensitivity, deactivation rate and channel open time are consistent with a reduced efficacy of channel gating, and would be expected to decrease GABAergic neurotransmission. The alpha1 subtype is the most widely expressed of the alpha subunits, with expression increasing throughout development. Therefore, production of the mutated subunit could cause global hyperexcitability throughout the brain, leading to generalized seizures with juvenile onset.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Fisher JLdoi
10.1016/j.neuropharm.2003.11.015subject
Has Abstractpub_date
2004-04-01 00:00:00pages
629-37issue
5eissn
0028-3908issn
1873-7064pii
S0028390803004441journal_volume
46pub_type
杂志文章abstract：:Neonatal administration of monosodium glutamate (MSG) destroyed perikarya in the arcuate nucleus and median eminence, including those that contain met-enkephalin and beta-endorphin and it increased the density of opiate receptors in the midbrain. Treatment with glutamate decreased the analgesic response on the jump te...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(84)90231-4
更新日期：1984-10-01 00:00:00
abstract：:Improgan is a chemical congener of the H2 antagonist cimetidine which shows the profile of a highly effective analgesic when administered directly into the CNS. Although the improgan receptor is unknown, improgan activates analgesic pathways which are independent of opioids, but may utilize cannabinoid mechanisms. To ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2006.04.003
更新日期：2006-09-01 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：:In this study, the role of CB₂r on aversive memory consolidation was further evaluated. Mice lacking CB₂r (CB2KO) and their corresponding littermates (WT) were exposed to the step-down inhibitory avoidance test (SDIA). MAP2, NF200 and synaptophysin (SYN)-immunoreactive fibers were studied in the hippocampus (HIP) of b...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2013.05.034
更新日期：2013-10-01 00:00:00
abstract：:Enhancement of GABAA receptor function with benzodiazepine (BZ) site agonists can disrupt memory formation and hippocampal synaptic plasticity. To investigate this further the effects of the agonist, flunitrazepam, were contrasted with that of the inverse agonist, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxyl...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(97)00040-3
更新日期：1997-06-01 00:00:00
abstract：:Visual cues that become associated with the consumption of psychostimulant drugs energize craving and the intake of the drug by mechanisms of which little is known. In two experiments using in vivo microdialysis in freely moving rats we compared the effects of visual and auditory stimulation with that of cocaine (0, 5...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2006.10.002
更新日期：2007-03-01 00:00:00
abstract：:Nitric oxide modulates pain development. However, there is no evidence on the effect of nitroxyl (HNO/NO⁻) in nociception. Therefore, we addressed whether nitroxyl inhibits inflammatory hyperalgesia and its mechanism using the nitroxyl donor Angeli's salt (AS; Na₂N₂O₃). Mechanical hyperalgesia was evaluated using a mo...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2013.03.009
更新日期：2013-08-01 00:00:00
abstract：:Prenatal exposure to the CB1 receptor agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)-pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone) mesylate (WIN) at a daily dose of 0.5 mg/kg, and Delta9-tetrahydrocannabinol (Delta9-THC) at a daily dose of 5 mg/kg, reduced dialysate glutamate levels in ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2007.05.019
更新日期：2007-09-01 00:00:00
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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：:The kynurenine pathway (KP) of tryptophan metabolism has emerged in recent years as a key regulator of the production of both neuroprotective (e.g. kynurenic and picolinic acid, and the essential cofactor NAD+) and neurotoxic metabolites (e.g. quinolinic acid, 3-hydroxykynurenine). The balance between the production o...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2016.03.024
更新日期：2017-01-01 00:00:00
abstract：:Conantokin-G (Con-G), a gamma-carboxylglutamate (Gla) containing peptide derived from the venom of the marine cone snail Conus geographus, acts as a selective and potent inhibitor of N-methyl-D-aspartate (NMDA) receptors. Here, the effect of Con-G on recombinant NMDA receptors carrying point mutations within the glyci...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(01)00112-5
更新日期：2001-11-01 00:00:00
abstract：:Up to 80% of cancer patients are affected by the cancer anorexia-cachexia syndrome (CACS), which leads to excessive body weight loss, reduced treatment success and increased lethality. The area postrema/nucleus of the solitary tract (AP/NTS) region emerged as a central nervous key structure in this multi-factorial pro...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2020.108289
更新日期：2020-12-01 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：:Maternal aggression is highly expressed during lactation and serves to protect the developing young from intruders that may injure the offspring. One neurochemical modulator of maternal aggression appears to be arginine vasopressin (AVP). Earlier research supports a role for AVP in maternal aggression in rats as treat...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2009.06.032
更新日期：2010-01-01 00:00:00
abstract：:alpha(2)-ARs regulate brain monoaminergic function by inhibiting neuronal firing and release of monoamine neurotransmitters, noradrenaline (NA), serotonin (5-HT) and dopamine (DA). Both alpha(2A)- and alpha(2C)-AR inhibit monoamine release in vitro in brain slices, but the in vivo roles of individual alpha(2)-AR subty...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(03)00080-7
更新日期：2003-06-01 00:00:00
abstract：:Rabbits anesthetized with volatile anesthetics were given bolus doses of the n-methyl-D-aspartate (NMDA) receptor antagonist MK-801. Following observation and recording of the hemodynamic and electroencephalographic effects of MK-801, the animals were tested for requirements of volatile anesthetic to prevent movement ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(89)90150-0
更新日期：1989-07-01 00:00:00
abstract：:Adrenergic-sensitive adenylate cyclase was found to be present in the nucleus accumbens and ventral caudate of the rabbit, but displayed less activity in the dorsal caudate. In general, stimulation of the enzyme by dopamine (DA) was most sensitive to inhibition by fluphenazine while norepinephrine (NE)-stimulated acti...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(84)90109-6
更新日期：1984-07-01 00:00:00
abstract：:Limited information exists on the link between purinergic class P2X7 receptors (P2X7Rs) and calcium ion channels in epilepsy; no data has been reported regarding the interaction between P2X7Rs and T-type calcium ion channels in epilepsy. Thus, this study is an evaluation of the role that T-type calcium ion channels pl...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2019.01.027
更新日期：2019-05-01 00:00:00
abstract：:The impairment of social behaviors induced by social defeat stress exposure as juveniles is resistant to some antidepressants and an antipsychotic, although the underlying mechanisms and/or therapeutic target are not yet clear. In this study, we investigated the involvement of the glutamatergic neuronal system in the ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.12.020
更新日期：2019-04-01 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：:Glutamatergic neurotransmission in the central nucleus of the amygdala (CeA) plays an important role in many behaviors including anxiety, memory consolidation and cardiovascular responses. While these behaviors can be modulated by corticotropin releasing factor (CRF) and catecholamine signaling, the mechanism(s) by wh...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2013.02.014
更新日期：2013-07-01 00:00:00
abstract：:Intrathecal (IT) injection of neostigmine (a cholinesterase inhibitor) has been reported to produce a significant anti-nociceptive effect in a number of inflammatory pain models. However, a potential anti-inflammatory effect of IT neostigmine in these models has not been investigated. In the present study, we have exa...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2004.12.024
更新日期：2005-09-01 00:00:00
abstract：:Data have been collected indicating possible functions for histamine in brain but there are only a very few data, collected exclusively with behavioural tests, about the effects of histamine on the perception of the pain, an important aspect in the homeostasis of the human body. The purpose of the present study was to...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(92)90133-a
更新日期：1992-09-01 00:00:00
abstract：:GABA(B) receptors inhibit and dopamine D1 receptors stimulate the release of GABA from striatal terminals in the pars reticulata of the substantia nigra. Here we have studied the interaction between both classes of receptors by exploring the effect of GABA(B) receptors upon the stimulation of depolarization-induced [(...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2007.07.014
更新日期：2007-10-01 00:00:00
abstract：:Hypotheses are scaffoldings erected in front of a building and then dismantled when the building is finished. They are indispensable for the workman; but you mustn't mistake the scaffolding for the building. Johann Wolfgang von Goethe. The neurogenesis hypothesis of affective disorders - in its simplest form - postula...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2011.09.003
更新日期：2012-01-01 00:00:00
abstract：:Tobacco addiction is a chronic disorder that is characterized by craving for tobacco products, withdrawal upon smoking cessation, and relapse after periods of abstinence. Previous studies demonstrated that systemic administration of α2-adrenergic receptor agonists attenuates stress-induced reinstatement of drug seekin...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2010.09.013
更新日期：2011-02-01 00:00:00
abstract：:The metabotropic glutamate receptor 5 (mGluR5) is a target for drug development and for imaging studies of the glutamate system in neurological and psychiatric disorders. [11C]AZD9272 is a selective mGluR5 PET radioligand that is structurally different from hitherto applied mGluR5 radioligands. In the present investig...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.03.039
更新日期：2018-06-01 00:00:00
abstract：:A history of intermittent exposures to drugs of abuse can cause long-term changes in acute behavioural responses to a subsequent drug exposure. In drug-naive rats, morphine can elicit intermittent cataleptic postures followed by sustained increases in locomotor activity. Chronic intermittent morphine treatment can red...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2009.01.003
更新日期：2009-03-01 00:00:00
abstract：:The effect of neurotrophic factors on apoptosis induced by ionomycin, a potent Ca2+ ionophore, was investigated using cultured cortical neurons from embryonic rats. Brain-derived neurotophic factor (BDNF) and neurotrophin-3 (NT-3) prevented the ionomycin-mediated cell death in a dose-dependent manner. In contrast to t...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(98)00189-0
更新日期：1999-02-01 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
