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Neuropharmacology

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https://www.readbyqxmd.com/read/28927993/voltage-gated-sodium-channel-%C3%AE-subunits-the-power-outside-the-pore-in-brain-development-and-disease
#1
REVIEW
Jacob M Hull, Lori L Isom
Voltage gated sodium channels (VGSCs) were first identified in terms of their role in the upstroke of the action potential. The underlying proteins were later identified as saxitoxin and scorpion toxin receptors consisting of α and β subunits. We now know that VGSCs are heterotrimeric complexes consisting of a single pore forming α subunit joined by two β subunits; a noncovalently linked β1 or β3 and a covalently linked β2 or β4 subunit. VGSC α subunits contain all the machinery necessary for channel cell surface expression, ion conduction, voltage sensing, gating, and inactivation, in one central, polytopic, transmembrane protein...
September 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28927992/protective-effects-of-the-glp-1-mimetic-exendin-4-in-parkinson-s-disease
#2
REVIEW
Dilan Athauda, Thomas Foltynie
There is increasing interest in the potential role of glucagon-like peptide-1 (GLP-1) receptor agonists as neuroprotective treatments in neurodegenerative diseases including Parkinson's disease following the publication of the results of the Exenatide-PD trial. Of the current GLP-1 receptor agonists already licensed to treat Type 2 diabetes several including exenatide, liraglutide and lixisenatide are the subject of ongoing clinical trials in PD. The underlying rationale for using drugs licensed and effective for T2DM in PD patients therefore needs to be scrutinized, and the results obtained to date critically reviewed...
September 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28923277/animal-models-of-ischaemic-stroke-and-characterisation-of-the-ischaemic-penumbra
#3
REVIEW
Christopher McCabe, Mariana M Arroja, Emma Reid, I Mhairi Macrae
Over the past forty years, animal models of focal cerebral ischaemia have allowed us to identify the critical cerebral blood flow thresholds responsible for irreversible cell death, electrical failure, inhibition of protein synthesis, energy depletion and thereby the lifespan of the potentially salvageable penumbra. They have allowed us to understand the intricate biochemical and molecular mechanisms within the 'ischaemic cascade' that initiate cell death in the first minutes, hours and days following stroke...
September 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28923278/can-adjunctive-therapies-augment-the-efficacy-of-endovascular-thrombolysis-a-potential-role-for-activated-protein-c
#4
REVIEW
Arun Paul Amar, Abhay P Sagare, Zhen Zhao, Yaoming Wang, Amy R Nelson, John H Griffin, Berislav V Zlokovic
In the management of acute ischemic stroke, vessel recanalization correlates with functional status, mortality, cost, and other outcome measures. Thrombolysis with intravenous tissue plasminogen activator has many limitations that restrict its applicability, but recent advances in the development of mechanical thrombectomy devices as well as improved systems of stroke care have resulted in greater likelihood of vessel revascularization. Nonetheless, there remains substantial discrepancy between rates of recanalization and rates of favorable outcome...
September 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28919080/regulation-of-glutamate-transporter-1-glt-1-gene-expression-by-cocaine-self-administration-and-withdrawal
#5
Ronald Kim, Marian T Sepulveda-Orengo, Kati L Healey, Emily A Williams, Kathryn J Reissner
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 withdrawal, with longer access to cocaine and longer withdrawal periods leading to greater decreases in GLT-1 protein. However, the mechanism(s) by which cocaine downregulates GLT-1 protein remains unknown...
September 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28917942/in-vivo-and-in-vitro-testing-of-native-%C3%AE-conotoxins-from-the-injected-venom-of-conus-purpurascens
#6
REVIEW
Mickelene F Hoggard, Alena M Rodriguez, Herminsul Cano, Evan Clark, Han-Shen Tae, David J Adams, Tanja A Godenschwege, Frank Marí
α-Conotoxins inhibit nicotinic acetylcholine receptors (nAChRs) and are used as probes to study cholinergic pathways in vertebrates. Model organisms, such as Drosophila melanogaster, express nAChRs in their CNS that are suitable to investigate the neuropharmacology of α-conotoxins in vivo. Here we report the paired nanoinjection of native α-conotoxin PIA and two novel α-conotoxins, PIC and PIC[O7], from the injected venom of Conus purpurascens and electrophysiological recordings of their effects on the giant fiber system (GFS) of D...
September 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28916331/depressive-like-phenotype-induced-by-prenatal-dexamethasone-in-mice-is-reversed-by-desipramine
#7
Mirko Conti, Stefan Spulber, Marilena Raciti, Sandra Ceccatelli
Exposure to prenatal insults has been associated with an increased risk for neuropsychiatric disorders, including depression, but the mechanisms are still poorly understood. Persistent alterations of the HPA axis feedback mechanism as well as adult impaired neurogenesis are believed to play a relevant role in the etiology of depression. In addition, growing evidence points at epigenetic reprogramming as a key factor. We have previously shown that prenatal exposure to the synthetic glucocorticoid dexamethasone (DEX) impairs neurogenesis and leads to late onset of depression-like behavior that does not respond to the SSRI antidepressant fluoxetine (FLX)...
September 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28911966/fluoxetine-administration-during-adolescence-attenuates-cognitive-and-synaptic-deficits-in-adult-3%C3%A3-tgad-mice
#8
Dong-Sheng Sun, Li-Feng Gao, Li Jin, Hao Wu, Qun Wang, You Zhou, Shuhao Fan, Xia Jiang, Dan Ke, Hao Lei, Jian-Zhi Wang, Gong-Ping Liu
Fluoxetine (FLX) has broad neurobiological functions and neuroprotective effects; however, the preventive effects of FLX on cognitive impairments in Alzheimer's disease (AD) have not been reported. Here, we studied whether adolescent administration of fluoxetine can prevent memory deficits in AD transgenic mice that harbour PS1m146v, APPswe and TauP301L mutations (3 × TgAD). FLX was applied through peritoneal injection to the mice at postnatal day 35 (p35) for 15 consecutive days, and the effects of FLX were observed at 6-month...
September 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28911965/physiological-roles-of-cns-muscarinic-receptors-gained-from-knockout-mice
#9
REVIEW
Morgane Thomsen, Gunnar Sørensen, Ditte Dencker
Because the five muscarinic acetylcholine receptor subtypes have overlapping distributions in many CNS tissues, and because ligands with a high degree of selectivity for a given subtype long remained elusive, it has been difficult to determine the physiological functions of each receptor. Genetically engineered knockout mice, in which one or more muscarinic acetylcholine receptor subtype has been inactivated, have been instrumental in identifying muscarinic receptor functions in the CNS, at the neuronal, circuit, and behavioral level...
September 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28899730/a-green-tea-polyphenol-epigallocatechin-3-gallate-enhances-neuroregeneration-after-spinal-cord-injury-by-altering-levels-of-inflammatory-cytokines
#10
Lucia Machova Urdzikova, Jiri Ruzicka, Kristyna Karova, Anna Kloudova, Barbora Svobodova, Anubhav Amin, Jana Dubisova, Meic Schmidt, Sarka Kubinova, Meena Jhanwar-Uniyal, Pavla Jendelova
Spinal cord injury (SCI) is a debilitating condition which is characterized by an extended secondary injury due to the presence of inflammatory local milieu. Epigallocatechin gallate (EGCG) appears to possess strong neuroprotective properties. Here, we evaluated the beneficial effect of EGCG on recovery from SCI. Male Wistar rats were given either EGCG or saline directly to the injured spinal cord and thereafter a daily IP injection. Behavior recovery was monitored by BBB, plantar, rotarod and flat-beam tests...
September 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28899729/serotonin-gating-of-cortical-and-thalamic-glutamate-inputs-onto-principal-neurons-of-the-basolateral-amygdala
#11
Ji-Dong Guo, Brendan M O'Flaherty, Donald G Rainnie
The basolateral amygdala (BLA) is a key site for crossmodal association of sensory stimuli and an important relay in the neural circuitry of emotion. Indeed, the BLA receives substantial glutamatergic inputs from multiple brain regions including the prefrontal cortex and thalamic nuclei. Modulation of glutamatergic transmission in the BLA regulates stress- and anxiety-related behaviors. Serotonin (5-HT) also plays an important role in regulating stress-related behavior through activation of both pre- and postsynaptic 5-HT receptors...
September 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28899728/maslinic-acid-ameliorates-nmda-receptor-blockade-induced-schizophrenia-like-behaviors-in-mice
#12
Se Jin Jeon, Eunji Kim, Jin Su Lee, Hee Kyong Oh, Jiabao Zhang, Yubeen Kwon, Dae Sik Jang, Jong Hoon Ryu
Schizophrenia is a chronic psychotic disorder characterized by positive, negative, and cognitive symptoms. Primary treatments for schizophrenia relieve the positive symptoms but are less effective against the negative and cognitive symptoms. In the present study, we investigated whether maslinic acid, isolated from Syzygium aromaticum (clove), can ameliorate schizophrenia-like behaviors in mice induced by MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist. After maslinic acid treatment in the MK-801 model, we examined the behavioral alteration and signaling pathways in the prefrontal cortex...
September 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28893562/positive-allosteric-modulation-of-m1-and-m4-muscarinic-receptors-as-potential-therapeutic-treatments-for-schizophrenia
#13
REVIEW
Samantha E Yohn, P Jeffrey Conn
Current antipsychotic drugs provide symptomatic relief for positive symptoms of schizophrenia, but do not offer symptom management for negative and cognitive symptoms. In addition, many patients discontinue treatment due to adverse side effects. Therefore, there is a critical need to develop more effective and safe treatment options. Although the etiology of schizophrenia is unclear, considerable data from post-mortem, neuroimaging and neuropharmacology studies support a role of the muscarinic acetylcholine (mAChRs) in the pathophysiology of schizophrenia...
September 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28890367/enhanced-anandamide-signaling-reduces-flight-behavior-elicited-by-an-approaching-robo-beetle
#14
Daniel E Heinz, Andreas Genewsky, Carsten T Wotjak
Our current knowledge of the implications of endocannabinoids in fear and anxiety is largely based on fear conditioning paradigms and approach-avoidance conflicts. Here we establish the ethobehavioral beetle mania task (BMT), which confronts mice with an erratically moving robo-beetle. With the help of this task we demonstrate decreased tolerance yet increased avoidance responses to an approaching beetle in high-anxiety behavior (HAB) and BALBc mice compared to C57BL/6N, CD1 and normal-anxiety behavior (NAB) mice...
September 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28890366/increasing-adult-hippocampal-neurogenesis-in-mice-after-exposure-to-unpredictable-chronic-mild-stress-may-counteract-some-of-the-effects-of-stress
#15
Luka Culig, Alexandre Surget, Marlene Bourdey, Wahid Khemissi, Anne-Marie Le Guisquet, Elise Vogel, Amar Sahay, René Hen, Catherine Belzung
Major depression is hypothesized to be associated with dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis and impairments in adult hippocampal neurogenesis. Adult-born hippocampal neurons are required for several effects of antidepressants and increasing the rate of adult hippocampal neurogenesis (AHN) before exposure to chronic corticosterone is sufficient to protect against its harmful effects on behavior. However, it is an open question if increasing AHN after the onset of chronic stress exposure would be able to rescue behavioral deficits and which mechanisms might be involved in recovery...
September 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28888944/the-novel-dopamine-d3-receptor-antagonists-partial-agonists-cab2-015-and-bak4-54-inhibit-oxycodone-taking-and-oxycodone-seeking-behavior-in-rats
#16
Zhi-Bing You, Jun-Tao Gao, Guo-Hua Bi, Yi He, Comfort Boateng, Jianjing Cao, Eliot L Gardner, Amy Hauck Newman, Zheng-Xiong Xi
The use of prescription opioid analgesics, particularly oxycodone, has dramatically increased, and parallels escalated opioid abuse and drug-related deaths worldwide. Understanding the molecular mechanisms underlying the development of opioid dependence and expanding treatment options to counter prescription opioid abuse has become a critical public health matter. In the present study, we first evaluated the reinforcing effects of oxycodone in a rat model of self-administration and then explored the potential utility of two novel high affinity dopamine D3 receptor (D3R) antagonists/partial agonists, CAB2-015 and BAK4-54, for treatment of prescription opioid abuse and dependence...
September 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28888943/melanin-concentrating-hormone-modulates-oxytocin-mediated-marble-burying
#17
Nayna M Sanathara, Celia Garau, Amal Alachkar, Lien Wang, Zhiwei Wang, Katsuhiko Nishimori, Xiangmin Xu, Olivier Civelli
Repetitive and perseverative behaviors are common features of a number of neuropsychiatric diseases such as Angelman's syndrome, Tourette's syndrome, obsessive-compulsive disorder, and autism spectrum disorders. The oxytocin system has been linked to the regulation of repetitive behavior in both animal models and humans, but many of its downstream targets have still to be found. We report that the melanin-concentrating hormone (MCH) system is a target of the oxytocin system in regulating one repetitive behavior, marble burying...
September 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28887185/role-of-monoaminergic-systems-and-ambient-temperature-in-bath-salts-constituent-3-4-methylenedioxypyrovalerone-mdpv-elicited-hyperthermia-and-locomotor-stimulation-in-mice
#18
REVIEW
Brenda M Gannon, Adrian Williamson, Kenner C Rice, William E Fantegrossi
3,4-Methylenedioxypyrovalerone (MDPV) is a common constituent of illicit bath salts products, and in vitro studies implicate monoamine transporters as mediators of its pharmacological effects. Locomotor and thermoregulatory effects of MDPV depend on ambient temperature, so the current studies aimed to gauge the involvement of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) in MDPV-induced locomotor stimulation and hyperthermia in the mouse at different ambient temperatures. Mice were pretreated with the selective 5-HT-reuptake inhibitor fluoxetine (3 mg/kg), the NE-reuptake inhibitor desipramine (3 mg/kg), the DA-reuptake inhibitor bupropion (10 mg/kg), or saline, followed by 10 mg/kg MDPV while thermoregulation and locomotor activity were monitored via radiotelemetry...
September 5, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28887184/chronic-fluoxetine-administration-enhances-synaptic-plasticity-and-increases-functional-dynamics-in-hippocampal-ca3-ca1-synapses
#19
Popova Dina, Eero Castren, Tomi Taira
Recent studies demonstrate that chronic administration of the widely used antidepressant fluoxetine (FLX) promotes neurogenesis, synaptogenesis and synaptic plasticity in the adult hippocampus, cortex and amygdala. However, the mechanisms underlying these effects and how are they related to the clinical antidepressant efficacy are still poorly understood. We show here that chronic FLX administration decreases hippocampus-associated neophobia in naïve mice. In parallel, electrophysiological recordings in hippocampal CA3-CA1 circuitry revealed that the FLX treatment resulted in increased short- and long-term plasticity likely attributed to changes in presynaptic function...
September 5, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28887183/electrical-stimulation-of-the-hippocampal-fimbria-facilitates-neuronal-nitric-oxide-synthase-activity-in-the-medial-shell-of-the-rat-nucleus-accumbens-modulation-by-dopamine-d1-and-d2-receptor-activation
#20
Kristina E Hoque, Shannon R Blume, Stephen Sammut, Anthony R West
The medial shell region of the nucleus accumbens (msNAc) is a key center for the regulation of goal-directed behavior and is likely to be dysfunctional in neuropsychiatric disorders such as addiction, depression and schizophrenia. Nitric oxide (NO)-producing interneurons in the msNAc are potently modulated by dopamine (DA) and may play an important role in synaptic integration in msNAc networks. In this study, neuronal NO synthase (nNOS) activity was measured in anesthetized rats using amperometric microsensors implanted into the msNAc or via histochemical techniques...
September 5, 2017: Neuropharmacology
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