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-inflammatory properties in rodent models of chronic neuropathic pain and inflammation, the effects of α7 nAChRs PAMs on chronic pain and inflammation remain largely unknown. The present study investigated whether PAMs, by increasing endogenous cholinergic tone, potentiate α7 nAChRs function to attenuate inflammatory and chronic neuropathic pain in mice. We tested two types of PAMS, type I (NS1738) and type II (PNU-120596) in carrageenan-induced inflammatory pain and chronic constriction injury (CCI) neuropathic pain models. We found that both NS1738 and PNU-120596 significantly reduced thermal hyperalgesia, while only PNU-120596 significantly reduced edema caused by a hind paw infusion of carrageenan. Importantly, PNU-120596 reversed established thermal hyperalgesia and edema induced by carrageenan. In the CCI model, PNU-120596 had long-lasting (up to 6 h), dose-dependent anti-hyperalgesic and anti-allodynic effects after a single injection, while NS1738 was inactive. Systemic administration of the α7 nAChR antagonist MLA reversed PNU-120596's effects, suggesting the involvement of central and peripheral α7 nAChRs. Furthermore, PNU-120596 enhanced an ineffective dose of selective agonist PHA-543613 to produce anti-allodynic effects in the CCI model. Our results indicate that the type II α7 nAChRs PAM PNU-120596, but not the type I α7 nAChRs PAM NS1738, shows significant anti-edematous and anti-allodynic effects in inflammatory and CCI pain models in mice.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Freitas K,Ghosh S,Ivy Carroll F,Lichtman AH,Imad Damaj Mdoi
10.1016/j.neuropharm.2012.08.022subject
Has Abstractpub_date
2013-02-01 00:00:00pages
156-64eissn
0028-3908issn
1873-7064pii
S0028-3908(12)00468-6journal_volume
65pub_type
杂志文章abstract：:Drugs modulating the levels of specific central neurotransmitters may influence both the rate and amount of functional recovery after focal brain injuries such as stroke. Because such drugs may be effective long after brain injury, the "therapeutic window" may be widened beyond the first few hour after stroke and an e...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0028-3908(99)00249-x
更新日期：2000-03-03 00:00:00
abstract：:The present study was designed to clarify whether α2-adrenoceptors of the basolateral amygdala (BLA) are involved in nicotine-induced anxiogenic-like behaviours. Adult male Wistar rats were bilaterally cannulated in the BLA and anxiety-like behaviours were assessed in an elevated plus maze (EPM) task. Systemic intrape...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.02.010
更新日期：2016-06-01 00:00:00
abstract：:Microdialysis studies in animals have shown that addictive drugs preferentially increase extracellular dopamine (DA) in the n. accumbens (NAc). Brain imaging studies, while extending these finding to humans, have shown a correlation between psychostimulant-induced increase of extracellular DA in the striatum and self-...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2004.06.032
更新日期：2004-01-01 00:00:00
abstract：:In rat brain, the number of beta-adrenoceptors and activity of noradrenaline-dependent adenylate cyclase were examined after treatment with desipramine (7.5 mg kg-1 day-1) for three days alone or in combination with the alpha 2-adrenoceptor antagonist, yohimbine (2 mg kg-1 12 hr-1), or with phenoxybenzamine (7.5 mg kg...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(84)90077-7
更新日期：1984-12-01 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：:5-hydroxytryptamine 1 (5-HT1) receptor blockade in combination with serotonin reuptake inhibition may provide a more rapid elevation of synaptic 5-HT compared to serotonin reuptake alone, by blocking the inhibitory effect of 5-HT1 receptor activation on serotonin release. GSK588045 is a novel compound with antagonist ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2014.11.017
更新日期：2015-05-01 00:00:00
abstract：:Carbenoxolone (CBX), the succinyl ester of glycyrrhetinic acid, is an inhibitor of gap junctional intercellular communication. Systemic administration of CBX was able to decrease the seizure severity score and to increase the latency time of seizure onset in genetically epilepsy prone rats (GEPRs). In particular, intr...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2004.08.021
更新日期：2004-12-01 00:00:00
abstract：:Systemic treatment with cholecystokinin octapeptide (CCK-8, 2.5-10 micrograms/kg, s.c.), a non-selective CCK agonist, decreased the exploratory activity of mice in an elevated plus-maze. At higher doses (5-10 micrograms/kg) CCK-8 reduced the frequency of rearing, but only 10 micrograms/kg of CCK-8 significantly inhibi...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(94)90112-0
更新日期：1994-06-01 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：:The effect of drugs which down-regulate the function of GABA at the level of the GABA/benzodiazepine receptor complex was studied on the conflict test in the rat. The GABA receptor antagonist, bicuculline, and the blockers of the GABA-receptor-coupled chloride channel, picrotoxin and pentylenetetrazol, produced a dose...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(86)90181-4
更新日期：1986-05-01 00:00:00
abstract：:Voltage sensitivity has been demonstrated for some GPCRs. At the dopamine D(2S) receptor, this voltage sensitivity is agonist-specific; some agonists, including dopamine, exhibit decreased potency at depolarized potentials, whereas others are not significantly affected. In the present study, we examined some of the re...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2011.06.022
更新日期：2011-10-01 00:00:00
abstract：:Regional differences are known in the serotonin-induced modulation of neuronal activity within the amygdala. This in vitro study in rats focuses on analyzing the ionic mechanism underlying serotonin-induced depolarization in the lateral amygdala. Serotonin depolarized membrane potential by 5 mV, which is underlain by ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2014.03.007
更新日期：2014-07-01 00:00:00
abstract：:The effect of acute exposure to alcohols on ion current mediated by recombinant 5-HT3RA receptors transiently expressed in human embryonic kidney 293 cells was investigated. Cells transfected with 5-HT3RA cDNA expressed receptors with pharmacological and functional properties similar to those of native 5-HT3 receptors...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(94)90131-7
更新日期：1994-12-01 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
abstract：:In the present studies, an attempt was made to elucidate the role of endogenous opioid inputs to the depressor region of the caudal ventrolateral medulla in the tonic regulation of arterial pressure and to examine the subtype(s) of receptor underlying any observed effects by use of receptor-specific antagonists. The d...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(91)90064-i
更新日期：1991-04-01 00:00:00
abstract：:This study examined the role of cannabinoid CB1 receptors (CB1r) in aggressive behavior. Social encounters took place in grouped and isolated mice lacking CB1r (CB1KO) and in wild-type (WT) littermates. Cognitive impulsivity was evaluated in the delayed reinforcement task (DRT). Gene expression analyses of monoaminoox...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2013.07.013
更新日期：2013-12-01 00:00:00
abstract：:This review will provide an overview of the non-drug based approaches that have been demonstrated to enhance cognitive function of the compromised brain, primarily focussed on the two most widely adopted paradigms of environmental enrichment and enhanced physical exercise. Environmental enrichment involves the generat...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2012.06.029
更新日期：2013-01-01 00:00:00
abstract：:The discovery of brain tumor-derived cells (BTSC) with the properties of stem cells has led to the formulation of the hypothesis that neural stem cells could be the cell of origin of primary brain tumors (PBT). In this review we present the most common molecular changes in PBT, define the criteria of identification of...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2009.12.019
更新日期：2010-05-01 00:00:00
abstract：:Gastrin-releasing peptide (GRP) receptor-expressing (GRPR)+ neurons have a central role in the spinal transmission of itch. Because their fundamental regulatory mechanisms are not yet understood, it is important to determine how such neurons are excited and integrate itch sensation. In this study, we investigated the ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2020.108025
更新日期：2020-06-15 00:00:00
abstract：:Inflammation plays a central role in the processes associated with neurodegeneration. The inflammatory response is mediated by activated microglia that release inflammatory mediators to the neuronal environment. Microglia-derived lysosomal cathepsins, including cathepsin X, are increasingly recognized as important med...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.11.019
更新日期：2017-03-01 00:00:00
abstract：:The effect of U-50,488H, a selective kappa opioid receptor agonist on the intake of food in food-deprived and non-deprived spontaneously hypertensive and normotensive Wistar-Kyoto rats was determined. In food deprived Wistar-Kyoto rats, intraperitoneal administration of U-50,488H, produced a bell-shaped curve on the i...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(89)90069-5
更新日期：1989-01-01 00:00:00
abstract：:The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the synthesis and release of dopamine (DA) was investigated in the retina of the rabbit in vitro. The results indicated that MPTP did not affect the synthesis of DA, but increased its release. Blockade of the activity of monoamine oxidase (MAO) with...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(87)90009-8
更新日期：1987-11-01 00:00:00
abstract：:Pyrantel is an anthelmintic which acts as an agonist of nicotinic receptors (AChRs) of nematodes and exerts its therapeutic effects by depolarizing their muscle membranes. Here we explore at the single-channel level the action of pyrantel at mammalian muscle AChR. AChR currents are elicited by pyrantel. However, openi...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(01)00057-0
更新日期：2001-08-01 00:00:00
abstract：:Disruption of reproductive function is a hallmark of abuse of anabolic androgenic steroids (AAS) in female subjects. To understand the central actions of AAS, patch clamp recordings were made in estrous, diestrous and AAS-treated mice from gonadotropin releasing hormone (GnRH) neurons, neurons in the medial preoptic a...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2011.05.008
更新日期：2011-09-01 00:00:00
abstract：:Systemic administration of thiazolidinediones reduces peripheral inflammation in vivo, presumably by acting at peroxisome proliferator-activated receptor gamma (PPARgamma) in peripheral tissues. Based on a rapidly growing body of literature indicating the CNS as a functional target of PPARgamma actions, we postulated ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2009.10.008
更新日期：2010-02-01 00:00:00
abstract：:The effects of nefiracetam on GABA-induced chloride currents were studied with rat dorsal root ganglion neurons in primary culture using the whole-cell patch-clamp technique. The dose-response curve for GABA-induced currents was shifted by 16 microM to lower concentrations by 10 microM nefiracetam while the maximal re...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(96)00074-3
更新日期：1996-01-01 00:00:00
abstract：:Lithium has been reported to exert neuroprotective activity in several neuronal cell cultures and in vivo models against glutamate toxicity. Since this action was reported to be associated with alterations in the antiapoptotic Bcl-2 family proteins, the effect of chronic lithium diet on the ability of the parkinsonism...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2004.02.005
更新日期：2004-06-01 00:00:00
abstract：:Calcium modulates the 5-HT3 receptor response by reducing peak current amplitude and increasing rates of activation, deactivation and desensitisation, but the binding site(s) and mechanism(s) of this modulation are unknown. Here we study residues that may be involved in calcium binding in two partially overlapping reg...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2008.07.009
更新日期：2009-01-01 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：: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
