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Neuropharmacology

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https://www.readbyqxmd.com/read/28108359/synaptic-targets-chronic-alcohol-actions
#1
REVIEW
Marisa Roberto, Florence Varodayan
Alcohol acts on numerous cellular and molecular targets to regulate neuronal communication within the brain. Chronic alcohol exposure and acute withdrawal generate prominent neuroadaptations at synapses, including compensatory effects on the expression, localization and function of synaptic proteins, channels and receptors. The present article reviews the literature describing the synaptic effects of chronic alcohol exposure and their relevance for synaptic transmission in the central nervous system. This review is not meant to be comprehensive, but rather to highlight the effects that have been observed most consistently and that are thought to contribute to the development of alcohol dependence and the negative aspects of withdrawal...
January 17, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28108358/neurochemical-and-metabolic-effects-of-acute-and-chronic-alcohol-in-the-human-brain-studies-with-positron-emission-tomography
#2
REVIEW
Nora D Volkow, Corinde E Wiers, Ehsan Shokri-Kojori, Dardo Tomasi, Gene-Jack Wang, Ruben Baler
The use of Positron emission tomography (PET) to study the effects of acute and chronic alcohol on the human brain has enhanced our understanding of the mechanisms underlying alcohol's rewarding effects, the neuroadaptations from chronic exposure that contribute to tolerance and withdrawal, and the changes in fronto-striatal circuits that lead to loss of control and enhanced motivation to drink that characterize alcohol use disorders (AUD). These include studies showing that alcohol's reinforcing effects may result not only from its enhancement of dopaminergic, GABAergic and opioid signaling but also from its caloric properties...
January 17, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28108357/sigma-1-receptor-deficiency-reduces-gabaergic-inhibition-in-the-basolateral-amygdala-leading-to-ltd-impairment-and-depressive-like-behaviors
#3
Baofeng Zhang, Ling Wang, Tingting Chen, Juan Hong, Sha Sha, Jun Wang, Hang Xiao, Ling Chen
Sigma-1 receptor knockout (σ1R-/-) in male mice causes depressive-like phenotype. We observed the expression of σ1R in principal neurons of basolateral amygdala (BLA), a main region for affective regulation. The present study investigated the influence of σ1R deficiency in BLA neurons on synaptic properties and plasticity at cortico-BLA pathway. In comparison with wild-type (WT) mice, the slopes of field excitatory postsynaptic potentials (fEPSP) were reduced in σ1R-/- mice with the increases in paired-pulse facilitation (PPF) and paired-pulse inhibition (PPI) values...
January 17, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28093211/pharmacological-properties-of-sak3-a-novel-t-type-voltage-gated-ca-2-channel-enhancer
#4
Yasushi Yabuki, Kazuya Matsuo, Hisanao Izumi, Hidaka Haga, Takashi Yoshida, Minoru Wakamori, Akira Kakehi, Kenji Sakimura, Takaichi Fukuda, Kohji Fukunaga
T-type voltage-gated Ca(2+) channels (T-VGCCs) function in the pathophysiology of epilepsy, pain and sleep. However, their role in cognitive function remains unclear. We previously reported that the cognitive enhancer ST101, which stimulates T-VGCCs in rat cortical slices, was a potential Alzheimer's disease therapeutic. Here, we introduce a more potent T-VGCC enhancer, SAK3 (ethyl 8'-methyl-2',4-dioxo-2-(piperidin-1-yl)-2'H-spiro[cyclopentane-1,3'-imidazo [1,2-a]pyridin]-2-ene-3-carboxylate), and characterize its pharmacological properties in brain...
January 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28093210/neuroprotection-by-paeoniflorin-in-the-mptp-mouse-model-of-parkinson-s-disease
#5
Meizhu Zheng, Chunming Liu, Yajun Fan, Pan Yan, Dongfang Shi, Yuchi Zhang
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/caspase-3 pathway. The objectives of the present study were to explore the potential neuroprotective effect of PF in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated mouse model of Parkinson's disease (PD)...
January 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28089847/the-binding-orientation-of-epibatidine-at-%C3%AE-7-nach-receptors
#6
Andrew J Thompson, Simon Metzger, Martin Lochner, Marc-David Ruepp
Epibatidine is an alkaloid toxin that binds with high affinity to nicotinic and muscarinic acetylcholine receptors, and has been extensively used as a research tool. To examine binding interactions at the nicotinic receptor, it has been co-crystallised with the structural homologue acetylcholine binding protein (AChBP; PDB ID 2BYQ), and with an AChBP chimaera (3SQ6) that shares 64% sequence identity with the α7 nACh receptor. However, the binding orientations revealed by AChBP co-crystal structures may not precisely represent their receptor homologues and experimental evidence is needed to verify the ligand poses...
January 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28089846/modulation-of-neuroinflammation-and-pathology-in-the-5xfad-mouse-model-of-alzheimer-s-disease-using-a-biased-and-selective-beta-1-adrenergic-receptor-partial-agonist
#7
Pooneh Memar Ardestani, Andrew K Evans, Bitna Yi, Tiffany Nguyen, Laurence Coutellier, Mehrdad Shamloo
Degeneration of noradrenergic neurons occurs at an early stage of Alzheimer's Disease (AD). The noradrenergic system regulates arousal and learning and memory, and has been implicated in regulating neuroinflammation. Loss of noradrenergic tone may underlie AD progression at many levels. We have previously shown that acute administration of a partial agonist of the beta-1 adrenergic receptor (ADRB1), xamoterol, restores behavioral deficits in a mouse model of AD. The current studies examined the effects of chronic low dose xamoterol on neuroinflammation, pathology, and behavior in the pathologically aggressive 5XFAD transgenic mouse model of AD...
January 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28089845/therapeutic-hypothermia-turning-humans-into-cold-blooded-ectotherms-via-adenosine-receptors
#8
Mirko Muzzi, Daniela Buonvicino, Alberto Chiarugi
No abstract text is available yet for this article.
January 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28088358/the-peroxisome-proliferator-activated-receptor-alpha-agonist-fenofibrate-attenuates-alcohol-self-administration-in-rats
#9
Colin N Haile, Therese A Kosten
Fibrates are a class of medications used to treat hypercholesterolemia and dyslipidemia that target nuclear peroxisome proliferator-activated receptors (PPARs). Studies have shown the PPARα agonist fenofibrate decreases voluntary EtOH consumption however its impact on the reinforcing and motivational effects of EtOH is unknown. We evaluated the ability of fenofibrate (25, 50 and 100 mg/kg), to alter EtOH (10%, w/v) and sucrose (2%, w/v) operant self-administration in rats under a FR2 schedule of reinforcement over four days and under a progressive ratio (PR) schedule on day five of treatment...
January 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28087359/the-effect-of-nmda-r-antagonism-on-simultaneously-acquired-local-field-potentials-and-tissue-oxygen-levels-in-the-brains-of-freely-moving-rats
#10
John Kealy, Sean Commins, John P Lowry
Non-competitive NMDA receptor antagonists are known to induce psychosis-like symptoms in rodents. Administration of such compounds cause behavioural effects such as memory impairment and hyperlocomotion. Additionally, drugs such as phencyclidine (PCP), ketamine and MK-801 all cause distinctive increases in striatal local field potential (LFP) in the high frequency oscillation (HFO) band in the power spectrum (140-180 Hz). Amperometric sensors provide a means to measure tissue oxygen (tO2; a BOLD-like signal) in the brains of freely-moving rats while simultaneously acquiring LFP using the same electrode...
January 10, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28082183/effects-of-p2x7-receptor-antagonists-on-hypoxia-induced-neonatal-seizures-in-mice
#11
Natalia Rodriguez-Alvarez, Eva M Jimenez-Mateos, Tobias Engel, Sean Quinlan, Cristina R Reschke, Ronán M Conroy, Anindya Bhattacharya, Geraldine B Boylan, David C Henshall
Neonatal seizures are a common consequence of hypoxic/ischemic encephalopathy (HIE). Phenobarbital remains the frontline treatment for neonatal seizures but is often ineffective. The P2X7 receptor (P2X7R) is a cell surface-expressed ionotropic receptor activated by high amounts of ATP which may be released during seizures or as a consequence of tissue injury. Here, we explored the role of the P2X7R in a mouse model of neonatal seizures induced by hypoxia. Exposure of postnatal day 7 (P7) mouse pups to global hypoxia (5% O2 for 15 min) produced electrographically-defined seizures with behavioural correlates that persisted after restitution of normoxia...
January 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28077289/vitamin-d3-protects-against-a%C3%AE-peptide-cytotoxicity-in-differentiated-human-neuroblastoma-sh-sy5y-cells-a-role-for-s1p1-p38mapk-atf4-axis
#12
Federica Pierucci, Mercedes Garcia-Gil, Alessia Frati, Francesca Bini, Maria Martinesi, Eleonora Vannini, Marco Mainardi, Federico Luzzati, Paolo Peretto, Matteo Caleo, Elisabetta Meacci
Besides its classical function of bone metabolism regulation, 1alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3), acts on a variety of tissues including the nervous system, where the hormone plays an important role as neuroprotective, antiproliferating and differentiating agent. Sphingolipids are bioactive lipids that play critical and complex roles in regulating cell fate. In the present paper we have investigated whether sphingolipids are involved in the protective action of 1,25(OH)2D3. We have found that 1,25(OH)2D3 prevents amyloid-β peptide (Aβ(1-42)) cytotoxicity both in differentiated SH-SY5Y human neuroblastoma cells and in vivo...
January 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28069353/effects-of-chronic-exposure-to-low-dose-thip-on-brainstem-neuronal-excitability-in-mouse-models-of-rett-syndrome-evidence-from-symptomatic-females
#13
Weiwei Zhong, Christopher Mychal Johnson, Ningren Cui, Hao Xing, Yang Wu, Chun Jiang
Rett Syndrome (RTT) is a neurodevelopmental disorder caused by mutations of the MECP2 gene, affecting predominantly females. One of the characteristic features of the disease is defective brainstem autonomic function. In Mecp2(-/Y) mice, several groups of brainstem neurons are overly excitable, which causes destabilization of neuronal networks for the autonomic control. We have previously shown that the extrasynaptic GABAA receptor agonist THIP relieves many RTT-like symptoms in Mecp2(-/Y) mice. Although neuronal activity is inhibited by acute THIP exposure, how a chronic treatment affects neuronal excitability remains elusive...
January 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28065587/ffpm-a-pde4-inhibitor-reverses-learning-and-memory-deficits-in-app-ps1-transgenic-mice-via-camp-pka-creb-signaling-and-anti-inflammatory-effects
#14
Haibiao Guo, Yufang Cheng, Canmao Wang, Jingang Wu, Zhengqiang Zou, Bo Niu, Hui Yu, Haitao Wang, Jiangping Xu
Thus far, phosphodiesterase-4 (PDE4) inhibitors have not been approved for application in Alzheimer's disease (AD) in a clinical setting due to severe side effects, such as nausea and vomiting. In this study, we investigated the effect of FFPM, a novel PDE4 inhibitor, on learning and memory abilities, as well as the underlying mechanism in the APP/PS1 mouse model of AD. Pharmacokinetic studies have revealed that FFPM efficiently permeates into the brain, and reached peak values in plasma 2 h after orally dosing...
January 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28062185/allicin-protects-auditory-hair-cells-and-spiral-ganglion-neurons-from-cisplatin-induced-apoptosis
#15
Xianmin Wu, Xiaofei Li, Yongdong Song, He Li, Xiaohui Bai, Wenwen Liu, Yuechen Han, Lei Xu, Jianfeng Li, Daogong Zhang, Haibo Wang, Zhaomin Fan
Cisplatin is a broad-spectrum anticancer drug that is commonly used in the clinic. Ototoxicity is one of the major side effects of this drug, which caused irreversible sensorineural hearing loss. Allicin, the main biologically active compound derived from garlic, has been shown to exert various anti-apoptotic and anti-oxidative activities in vitro and in vivo studies. We took advantage of C57 mice intraperitoneally injected with cisplatin alone or with cisplatin and allicin combined, to investigate whether allicin plays a protective role in vivo against cisplatin ototoxicity...
January 3, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28042019/endomorphin-2-analogs-with-c-terminal-esterification-produce-potent-systemic-antinociception-with-reduced-tolerance-and-gastrointestinal-side-effects
#16
Chang-Lin Wang, Ting-Ting Qiu, Dai-Jun Yang, Bi-Yu Yuan, Feng-Tong Han, Li Li, Ning Gu
C-terminal esterification of opioid peptides may change their opioid activities due to the modified physicochemical properties. In the present study, the pharmacological activities of C-terminal esterified endomorphin-2 (EM-2) analogs 1-3 were characterized by in vitro metabolic stability and octanol/buffer distribution assays. Also, the antinociceptive profiles in the radiant heat paw withdrawal test and related side effects of these analogs were determined. Our results showed that all three analogs significantly increased the metabolic stability and lipophilicity...
December 29, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/28039001/paliperidone-reverts-toll-like-receptor-3-signaling-pathway-activation-and-cognitive-deficits-in-a-maternal-immune-activation-mouse-model-of-schizophrenia
#17
Karina S MacDowell, Eva Munarriz-Cuezva, Javier R Caso, José L M Madrigal, Arantzazu Zabala, J Javier Meana, Borja García-Bueno, Juan C Leza
The pathophysiology of psychotic disorders is multifactorial, including alterations in the immune system caused by exogenous or endogenous factors. Epidemiological and experimental studies indicate that infections during the gestational period represent a risk factor to develop schizophrenia (SZ) along lifetime. Here, we tested the hypothesis that the antipsychotic paliperidone regulates immune-related brain effects in an experimental model of SZ. A well described prenatal immune activation model of SZ in mice by maternal injection of the viral mimetic poly(I:C) during pregnancy was used...
December 28, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/28025096/early-vs-late-intervention-of-high-fat-low-dose-streptozotocin-treated-c57bl-6j-mice-with-enalapril-%C3%AE-lipoic-acid-menhaden-oil-or-their-combination-effect-on-diabetic-neuropathy-related-endpoints
#18
Matthew S Yorek, Alexander Obrosov, Hanna Shevalye, Lawrence J Coppey, Randy H Kardon, Mark A Yorek
We have previously demonstrated that enalapril, α-lipoic acid and menhaden (fish) oil has potential as a treatment for diabetic peripheral neuropathy. In this study we sought to determine the efficacy of these treatments individually or in combination on multiple neuropathic endpoints in a high fat fed low dose streptozotocin treated mouse, a model of type 2 diabetes, following early or late intervention. Four or twelve weeks after the onset of hyperglycemia, diabetic mice were treated with enalapril, α-lipoic acid, menhaden oil or their combination for 12 weeks...
December 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/28025095/a-cross-species-study-of-heterogeneity-in-fear-extinction-learning-in-relation-to-fkbp5-variation-and-expression-implications-for-the-acute-treatment-of-posttraumatic-stress-disorder
#19
Isaac R Galatzer-Levy, Raül Andero, Takehito Sawamura, Tanja Jovanovic, Santiago Papini, Kerry J Ressler, Seth Davin Norrholm
Deficits in fear extinction learning are hypothesized to underlie the development of posttraumatic stress disorder (PTSD). Such deficits may, in part, be due to genetic and epigenetic variation in the stress related gene FKBP5. Conversely, altering FKBP5 epigenetic responses during memory consolidation may rescue extinction deficits making it a target for acute intervention to prevent the development of PTSD. Study 1 (Humans) examines if FKBP5 single nucleotide polymorphisms (SNPs) and PTSD symptom domains (re-experiencing, avoidance/numbing, hyperarousal) are associated with abnormal fear extinction phenotypes identified using latent growth mixture modeling (LGMM)...
December 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/28025094/serotonergic-mechanisms-of-trigeminal-meningeal-nociception-implications-for-migraine-pain
#20
Erkan Kilinc, Cindy Guerrero-Toro, Andrey Zakharov, Carmela Vitale, Max Gubert-Olive, Ksenia Koroleva, Arina Timonina, Liliana L Luz, Irina Shelukhina, Raisa Giniatullina, Fatma Tore, Boris V Safronov, Rashid Giniatullin
Serotonergic mechanisms play a central role in migraine pathology. However, the region-specific effects of serotonin (5-HT) mediated via multiple types of receptors in the nociceptive system are poorly understood. Using extracellular and patch-clamp recordings, we studied the action of 5-HT on the excitability of peripheral and central terminals of trigeminal afferents. 5-HT evoked long-lasting TTX-sensitive firing in the peripheral terminals of meningeal afferents, the origin site of migraine pain. Cluster analysis revealed that in majority of nociceptive fibers 5-HT induced either transient or persistent spiking activity with prevailing delta and theta rhythms...
December 23, 2016: Neuropharmacology
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