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 causally related to cognitive deficits in SZ and other psychiatric diseases. As dysfunction of circuits involving GABAergic neurons in the prefrontal cortex (PFC) likely plays a role in the cognitive impairments seen in these disorders, we examined the effects of KYNA on extracellular GABA in this brain area. Applied to awake rats for 2 h by reverse dialysis, KYNA concentration-dependently and reversibly reduced extracellular GABA levels, with 300 nM KYNA causing a nadir of ∼45% of baseline concentrations. This effect was not duplicated by reverse dialysis of the selective glycineB receptor antagonist 7-Cl-KYNA (100 nM) or the AMPA/kainate receptor antagonist CNQX (100 μM), and was prevented by co-application of galantamine (5 μM), a positive allosteric modulator of the α7nAChR. Conversely, inhibition of endogenous KYNA formation by reverse dialysis of (S)-4-(ethylsulfonyl)benzoylalanine (ESBA; 5 mM) reversibly increased GABA levels in the PFC, reaching a peak of ∼160% of baseline concentrations. Co-infusion of 30 nM KYNA neutralized this effect. Taken together, these results demonstrate a role for endogenous KYNA in the bi-directional control of GABAergic neurotransmission in the PFC. Pharmacological manipulation of KYNA may therefore be useful in the treatment of GABAergic impairments in SZ and other brain disorders involving the PFC.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Beggiato S,Tanganelli S,Fuxe K,Antonelli T,Schwarcz R,Ferraro Ldoi
10.1016/j.neuropharm.2014.02.019subject
Has Abstractpub_date
2014-07-01 00:00:00pages
11-8eissn
0028-3908issn
1873-7064pii
S0028-3908(14)00083-5journal_volume
82pub_type
杂志文章abstract::Dichlorvos is a synthetic insecticide that belongs to the family of chemically related organophosphate (OP) pesticides. It can be released into the environment as a major degradation product of other OPs, such as trichlorfon, naled, and metrifonate. Dichlorvos exerts its toxic effects in humans and animals by inhibiti...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2011.07.008
更新日期:2011-12-01 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::The aim of the present study was to investigate if different levels of circulating corticosterone (CORT) modulate the effect of nicotine on prepulse inhibition (PPI), a measure of sensorimotor gating that is disrupted in schizophrenia and other mental illnesses. Four groups of mice were investigated: sham-operated, ad...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2004.08.015
更新日期:2005-01-01 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::Mice that were rendered heterozygous for the γ2 subunit of GABAA receptors (γ2(+/-) mice) have been characterized extensively as a model for major depressive disorder. The phenotype of these mice includes behavior indicative of heightened anxiety, despair, and anhedonia, as well as defects in hippocampus-dependent pat...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2014.07.019
更新日期:2015-01-01 00:00:00
abstract::Agonists and positive allosteric modulators (PAMs) of α7 nicotinic acetylcholine receptors (nAChRs) are currently being considered as novel therapeutic approaches for managing cognitive deficits in schizophrenia and Alzheimer's disease. Though α7 agonists were recently found to possess antinociceptive and anti-inflamm...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2012.08.022
更新日期:2013-02-01 00:00:00
abstract::Synaptic input activity affects the neurogenesis in adult hippocampal dentate gyrus (DG), while the input activity is potentiated by neurosteroid pregnenolone sulfate (PREGS). This study focused on exploring the effects of PREGS on the survival of newborn neurons in the DG of adult male mice. Proliferating cells were ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2010.11.017
更新日期:2011-02-01 00:00:00
abstract::Venlafaxine, a novel 2-phenyl-2-(1-hydroxycycloalkyl) ethylamine, is a potent inhibitor of 5-hydroxytryptamine and noradrenaline reuptake and exhibits a profile of activity in pre-clinical in vitro biochemical studies predictive of antidepressant activity. The studies described here examined the effects of acute and c...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(93)90065-b
更新日期:1993-10-01 00:00:00
abstract::Parkinson's disease (PD) is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra, leading to motor symptoms. Despite the remarkable improvements in the management of PD in recent decades, many patients remain significantly disabled. Metformin is a primary me...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2020.108173
更新日期:2020-09-15 00:00:00
abstract::SKF 83959 that has a unique antiparkinson profile in animal models of Parkinson's disease is an in vitro dopamine D1 antagonist of receptors coupled to adenylyl cyclase. We hypothesized that SKF 83959, among others, interacts with dopamine D1 receptors coupled to adenylyl cyclase in the nucleus accumbens and the prefr...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(01)00169-1
更新日期:2002-02-01 00:00:00
abstract::Some phytochemical-derived synthetic compounds have been shown to improve neurological disorders, especially in ischemic stroke. In this study, we identified a novel biscoumarin compound, known as COM 3, which had substantial antioxidant effects in neurons. Next, we found that COM 3 occupies a critical binding site be...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2019.107918
更新日期:2020-05-01 00:00:00
abstract::The mechanisms underlying 3,4-methylenedioxymethamphetamine (MDMA)-induced serotonergic (5-HT) toxicity remain unclear. It has been suggested that MDMA depletes 5-HT by increasing brain tyrosine levels, which via non-enzymatic hydroxylation leads to DA-derived free radical formation. Because this hypothesis assumes th...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2008.01.007
更新日期:2008-04-01 00:00:00
abstract::Behavioural studies can help to validate, modify and refine schemes for classifying receptors that are developed from electrophysiological and biochemical experiments. Drug discrimination constitutes one family of behavioural techniques that is being extensively used for studying subtypes of receptors, mainly because ...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/0028-3908(87)90064-5
更新日期:1987-07-01 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::In view of the involvement of noradrenaline (NA) in the regulation of adrenocortical secretion, its role in the rise of plasma corticosterone following neural stimuli was evaluated in rats. The injection of the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) into the ventral noradrenergic bundle in the brain stem,...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(88)90161-x
更新日期:1988-02-01 00:00:00
abstract::Phenytoin (DPH) is a clinically useful sodium (Na) channel blocker with efficacy against partial and generalized seizures. We have developed a novel hydantoin compound (HA) using comparative molecular field analysis (CoMFA) and evaluated its effects on hNa(v)1.2 channels. Both DPH and HA demonstrated affinity for rest...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2006.11.001
更新日期:2007-03-01 00:00:00
abstract::The role of the adenosine A(2A) receptor in the hypnotic effects of ethanol was assessed in mice. The duration of the loss of righting reflex following acute ethanol administration was shorter for A(2A) receptor-deficient mice (A(2A)R KO) than for wild-type mice (A(2A)R WT), whereas the fall in body temperature was no...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(03)00254-5
更新日期:2003-12-01 00:00:00
abstract::A number of pre-clinical studies have shown that brain-generated acetaldehyde, the first metabolite of ethanol, exerts reinforcing effects that promote the acquisition of ethanol intake, while chronic intake maintenance appears to be mediated by alcohol-induced brain neuroinflammation/oxidative stress. Recently, it wa...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2018.12.001
更新日期:2019-03-01 00:00:00
abstract::A striking observation among veterans returning from the recent conflicts in Iraq and Afghanistan has been the co-occurrence of blast-related mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). PTSD and mTBI might coexist due to additive effects of independent psychological and physical traum...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2018.09.023
更新日期:2019-02-01 00:00:00
abstract::Momordica charantia (MC) is a medicinal plant for stroke treatment in Traditional Chinese Medicine, but its active compounds and molecular targets are unknown yet. M. charantia polysaccharide (MCP) is one of the important bioactive components in MC. In the present study, we tested the hypothesis that MCP has neuroprot...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2014.11.020
更新日期:2015-04-01 00:00:00
abstract::Increasingly in the realm of neurological disorders, particularly those involving neurodegeneration, mitochondrial dysfunction is emerging at the core of their pathogenic processes. Most of these diseases still lack effective treatment and are hampered by a shortfall in the development of novel medicines. Clearly new ...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2015.10.033
更新日期:2016-03-01 00:00:00
abstract::The nucleus tractus solitarius (NTS) region in the rat has been shown to receive arginine vasopressin (AVP) and oxytocin (OT) neurophysin-containing neuronal projections from the suprachiasmatic (SNC) and paraventricular nucleus (PVN). Thus, vasopressin and oxytocin might have central influences on the circulation. Th...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(82)90012-0
更新日期:1982-07-01 00:00:00
abstract::For a number of years it has been known that the CNS convulsant picrotoxin inhibits the GABA(A) receptor, an anion-selective member of the ligand-gated ion channel (LGIC) superfamily. PTX also inhibits other anion-selective LGIC members, such as GABA(C), glycine and glutamate-gated Cl(-) channels. In the present repor...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(03)00032-7
更新日期:2003-03-01 00:00:00
abstract::Extensive evidence indicates that noradrenergic activation of the basolateral amygdala (BLA) is essential for mediating emotional arousal effects on memory consolidation in different target regions. However, the mechanism by which BLA activation regulates such information storage processes remains largely elusive. Her...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2018.08.018
更新日期:2018-10-01 00:00:00
abstract::Cyclic nucleotides cAMP and cGMP cooperate to ensure memory acquisition and consolidation. Increasing their levels by phosphodiesterase inhibitors (PDE-Is) enhanced cognitive functions and rescued memory loss in different models of aging and Alzheimer's disease (AD). However, side effects due to the high doses used li...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2018.06.002
更新日期:2018-08-01 00:00:00
abstract::We report in this study a 2-aminoethoxydiphenyl borate (2-APB) activated Ca2+ pathway in NG115-401L (401L) neuronal cells bearing resemblance to hormonal and ryanodine receptor activated pathways. We observed that 2-APB, in contrast to much earlier work, did not inhibit store operated Ca2+ channel (SOC) function, but ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2005.10.011
更新日期:2006-04-01 00:00:00
abstract::Group III metabotropic glutamate receptors (mGluR4,7,8) are widely distributed in the basal ganglia. Injection of group III mGluR agonists into the striatopallidal complex alleviates parkinsonian symptoms in 6-hydroxydopamine-treated rats. In vitro rodent studies have suggested that this may be partly due to modulatio...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2012.05.017
更新日期:2013-03-01 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::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 schizop...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2015.08.003
更新日期:2017-03-15 00:00:00
abstract::The effects of d-amphetamine (0.03-10.0 mg/kg), caffeine (0.3-100.0 mg/kg), nicotine (0.003-10.0 mg/kg) and cocaine (0.03-56.0 mg/kg) were compared on responding maintained under three different schedules of food presentation in mice. Cumulative doses of d-amphetamine, nicotine and cocaine only decreased responding ma...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(86)90160-7
更新日期:1986-10-01 00:00:00