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Neuropharmacology

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https://www.readbyqxmd.com/read/29782876/chloride-cotransporter-kcc2-is-essential-for-gabaergic-inhibition-in-the-scn
#1
A H O Olde Engberink, J H Meijer, S Michel
One of the principal neurotransmitters of the central nervous system is GABA. In the adult brain, GABA is predominantly inhibitory, but there is growing evidence indicating that GABA can shift to excitatory action depending on environmental conditions. In the mammalian central circadian clock of the suprachiasmatic nucleus (SCN) GABAergic activity shifts from inhibition to excitation when animals are exposed to long day photoperiod. The polarity of the GABAergic response (inhibitory versus excitatory) depends on the GABA equilibrium potential determined by the intracellular Cl- concentration ([Cl- ]i )...
May 18, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29782875/a-tribute-to-norman-g-bowery
#2
EDITORIAL
Bernhard Bettler, Vincenzo Crunelli, S J Enna
No abstract text is available yet for this article.
May 18, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29782874/are-alzheimer-s-disease-and-other-neurodegenerative-disorders-caused-by-impaired-signalling-of-insulin-and-other-hormones
#3
EDITORIAL
Christian Hölscher, Fernanda G De Felice, Nigel Greig, Sergio T Ferreira
No abstract text is available yet for this article.
May 18, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29778944/activation-and-blockade-of-basolateral-amygdala-5-ht-6-receptor-produce-anxiolytic-like-behaviors-in-an-experimental-model-of-parkinson-s-disease
#4
Yi-Na Sun, Lu Yao, Li-Bo Li, Yong Wang, Cheng-Xue Du, Yuan Guo, Jian Liu
Although the basolateral amygdala (BLA) and serotonin6 (5-HT6 ) receptor are involved in modulation of anxiety, their roles in Parkinson' disease (PD)-related anxiety are still unknown. Thus we perform this study to examine the involvement of BLA 5-HT6 receptor on anxiety in unilateral 6-hydroxydopamine-induced PD rats. The lesion of the medial forebrain bundle (MFB) induced anxiety-like behaviors, and decreased the basal firing rate of BLA glutamate neurons and dopamine (DA) levels in tissues of the medial prefrontal cortex (mPFC), amygdala and ventral part of hippocampus (vHip) in rats...
May 17, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29778010/exposure-to-cannabinoid-agonist-win-55-212-2-during-early-adolescence-increases-alcohol-preference-and-anxiety-in-cd1-mice
#5
Jimena Laura Frontera, Victoria María Gonzalez Pini, Fernando Luis Messore, Alicia Brusco
The endocannabinoid (eCB) system is involved in the modulation of the reward system and participates in the reinforcing effects of different drugs of abuse, including alcohol. The most abundant receptor of the eCB system in the central nervous system is the CB1 receptor (CB1R), which is predominantly expressed in areas involved in drug addiction, such as the nucleus accumbens, the ventral tegmental area, the substantia nigra and the raphe nucleus. CB1R is expressed in early stages during development, and reaches maximum levels during early adolescence...
May 16, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29775679/identification-and-validation-of-midbrain-kcnq4-regulation-of-heavy-alcohol-consumption-in-rodents
#6
Natalie S McGuier, Jennifer A Rinker, Reginald Cannady, Diana B Fulmer, Sara R Jones, Michaela Hoffman, Patrick J Mulholland
Currently available pharmacotherapies for treating alcohol use disorder (AUD) suffer from deleterious side effects and are not efficacious in diverse populations. Clinical and preclinical studies provide evidence that the Kcnq family of genes that encode KV 7 channels influence alcohol intake and dependence. KV 7 channels are a class of slowly activating voltage-dependent K+ channels that regulate neuronal excitability. Studies indicate that the KV 7 channel positive modulator retigabine can decrease dopaminergic neuron firing, alter dopamine (DA) release, and reduce alcohol intake in heavy drinking rodents...
May 15, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29775678/synaptic-transmission-and-excitability-during-hypoxia-with-inflammation-and-reoxygenation-in-hippocampal-ca1-neurons
#7
Yoon-Sil Yang, Sook Jin Son, Joon Ho Choi, Jong-Cheol Rah
Although a number of experimental and clinical studies have shown that hypoxia typically accompanies acute inflammatory responses, the combinatorial effect of the two insults on basic neural function has not been thoroughly investigated. Previous studies have predominantly suggested that hypoxia reduces network activity; however, several studies suggest the opposite effect. Of note, inflammation is known to increase neural activity. In the current study, we examined the effects of limited oxygen in combination with an inflammatory stimulus, as well as the effects of reoxygenation, on synaptic transmission and excitability...
May 15, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29778946/mechanisms-underlying-anticonvulsant-and-proconvulsant-actions-of-norepinephrine
#8
REVIEW
Maedeh Ghasemi, Nasrin Mehranfard
Norepinephrine (NE) has been shown to exert a potent suppressant effect on seizure development. On the other hand, several lines of evidence have shown that increased NE level is proconvulsant under certain conditions. These data suggest that variations in NE levels could affect modulatory action of noradrenergic system on seizures. Less, however, is known about the mechanisms by which adrenergic pathways protect against seizures or promote seizures. Knowing the mechanisms involved in anti- or proconvulsive effects of NE may help to the development of new therapeutic candidates for patients with refractory epilepsy...
May 11, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29758221/inhibition-of-striatal-cholinergic-interneuron-activity-by-the-kv7-opener-retigabine-and-the-nonsteroidal-anti-inflammatory-drug-diclofenac
#9
Rodrigo Manuel Paz, Cecilia Tubert, Agostina Stahl, Analía López Díaz, Roberto Etchenique, Mario Gustavo Murer, Lorena Rela
Striatal cholinergic interneurons provide modulation to striatal circuits involved in voluntary motor control and goal-directed behaviors through their autonomous tonic discharge and their firing "pause" responses to novel and rewarding environmental events. Striatal cholinergic interneuron hyperactivity was linked to the motor deficits associated with Parkinson's disease and the adverse effects of chronic antiparkinsonian therapy like l-DOPA-induced dyskinesia. Here we addressed whether Kv7 channels, which provide negative feedback to excitation in other neuron types, are involved in the control of striatal cholinergic interneuron tonic activity and response to excitatory inputs...
May 11, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29753748/the-abuse-potential-of-medical-psilocybin-according-to-the-8-factors-of-the-controlled-substances-act
#10
REVIEW
Matthew W Johnson, Roland R Griffiths, Peter S Hendricks, Jack E Henningfield
This review assesses the abuse potential of medically-administered psilocybin, following the structure of the 8 factors of the US Controlled Substances Act (CSA). Research suggests the potential safety and efficacy of psilocybin in treating cancer-related psychiatric distress and substance use disorders, setting the occasion for this review. A more extensive assessment of abuse potential according to an 8 factor analysis would eventually be required to guide appropriate schedule placement. Psilocybin, like other 5-HT2A agonist classic psychedelics, has limited reinforcing effects, supporting marginal, transient non-human self-administration...
May 10, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29778945/self-administration-of-the-synthetic-cathinone-mpdv-enhances-reward-function-via-a-nicotinic-receptor-dependent-mechanism
#11
Jean R Geste, Marjory Pompilus, Marcelo Febo, Adriaan W Bruijnzeel
Methylenedioxypyrovalerone (MDPV) is an addictive synthetic drug with severe side effects. Previous studies have shown that MDPV has positive reinforcing properties. However, little is known about the effect of MDPV self-administration on the state of the brain reward system and the neuronal mechanisms by which MDPV mediates its effects. The goal of the present studies was to determine the effect of MDPV self-administration on reward function and the role of cholinergic neurotransmission in the reinforcing effects of MDPV...
May 9, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29753117/pharmacological-inhibition-of-receptor-protein-tyrosine-phosphatase-%C3%AE-%C3%AE-ptprz1-modulates-behavioral-responses-to-ethanol
#12
Rosalía Fernández-Calle, Marta Vicente-Rodríguez, Miryam Pastor, Esther Gramage, Bruno Di Geronimo, José María Zapico, Claire Coderch, Carmen Pérez-García, Amy W Lasek, Beatriz de Pascual-Teresa, Ana Ramos, Gonzalo Herradón
Pleiotrophin (PTN) and Midkine (MK) are neurotrophic factors that are upregulated in the prefrontal cortex after alcohol administration and have been shown to reduce ethanol drinking and reward. PTN and MK are the endogenous inhibitors of Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ (a.k.a. PTPRZ1, RPTPβ, PTPζ), suggesting a potential role for this phosphatase in the regulation of alcohol effects. To determine if RPTPβ/ζ regulates ethanol consumption, we treated mice with recently developed small-molecule inhibitors of RPTPβ/ζ (MY10, MY33-3) before testing them for binge-like drinking using the drinking in the dark protocol...
May 9, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29750979/ketamine-facilitates-extinction-of-avoidance-behavior-and-enhances-synaptic-plasticity-in-a-rat-model-of-anxiety-vulnerability-implications-for-the-pathophysiology-and-treatment-of-anxiety-disorders
#13
Ashley M Fortress, Ian M Smith, Kevin C H Pang
Anxiety disorders and posttraumatic stress disorder (PTSD) share a common feature of pathological avoidance behavior. The Wistar Kyoto (WKY) rat has been used as a model of anxiety vulnerability, expressing a behaviorally inhibited temperament, acquiring avoidance behavior more rapidly and displaying extinction-resistant avoidance compared to Sprague Dawley (SD) rats. Subanesthetic levels of ketamine have gained attention as a rapid antidepressant in treatment-resistant depression. While traditional antidepressants are commonly used to treat anxiety disorders and PTSD, the therapeutic utility of ketamine for these disorders is much less understood...
May 8, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29738851/intranasally-delivered-small-interfering-rna-mediated-suppression-of-scavenger-receptor-mac-1-attenuates-microglial-phenotype-switching-and-working-memory-impairment-following-hypoxia
#14
Sudeshna Das, K P Mishra, Lilly Ganju, S B Singh
Brain, being the highest consumer of oxygen, is prone to increased risk of hypoxia-induced neurological insults. In response to hypoxia, microglia, the major resident immune cells of brain switches to an activated phenotype and promote inflammatory responses leading to tissue damage and loss of cognitive functions including working memory impairment. Till date, no proven clinical therapeutics is available to retard the progression of neurodegenerative memory impairment. In the present study, we investigated the therapeutic potential of intranasal small interfering RNA (siRNA) delivery in a mouse model of hypoxia-induced working memory impairment using microglial receptor, Mac-1 as a target gene...
May 5, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29738850/intermittent-streptozotocin-administration-induces-behavioral-and-pathological-features-relevant-to-alzheimer-s-disease-and-vascular-dementia
#15
Andrew S Murtishaw, Chelcie F Heaney, Monica M Bolton, Krystal Courtney D Belmonte, Michael A Langhardt, Jefferson W Kinney
RATIONALE: Diabetes mellitus (DM) is a major risk factor for Alzheimer's disease and vascular dementia. Few animal models exist that focus on the metabolic contributions to dementia onset and progression. Thus, there is strong scientific rationale to explore the effects of streptozotocin (STZ), a diabetogenic compound, on vascular and inflammatory changes within the brain. OBJECTIVE AND METHODS: The present study was designed to evaluate the effect of staggered, low-dose administration of STZ on behavioral and cognitive deficits, neuroinflammation, tau pathology, and histopathological alterations related to dementia...
May 5, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29738849/5-ht-1a-receptor-stimulation-in-the-medial-prefrontal-cortex-mediates-the-antidepressant-effects-of-mglu2-3-receptor-antagonist-in-mice
#16
Kenichi Fukumoto, Michihiko Iijima, Takeo Funakoshi, Shigeyuki Chaki
We previously reported that serotonergic transmission is involved in the antidepressant effects of metabotropic glutamate 2/3 (mGlu2/3) receptor antagonists. However, the detailed underlying mechanisms had not yet been explored. In the present study, we investigated the role of the 5-HT1A receptor and its signaling cascade in the medial prefrontal cortex (mPFC) in the antidepressant effects of LY341495, an mGlu2/3 receptor antagonist. LY341495 significantly reduced the immobility time in the forced swimming test which sustained for 24 h after administration...
May 5, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29772491/calpain-inhibition-reduces-nmda-receptor-rundown-in-rat-substantia-nigra-dopamine-neurons
#17
Jerry Zhao, Michel Baudry, Susan Jones
Repeated activation of N-Methyl-d-aspartate receptors (NMDARs) causes a Ca2+ -dependent reduction in NMDAR-mediated current in dopamine (DA) neurons of the substantia nigra pars compacta (SNc) in one week old rats; however, a Ca2+ -dependent regulatory protein has not been identified. The role of the Ca2+ -dependent cysteine protease, calpain, in mediating NMDAR current rundown was investigated. In brain slices from rats aged postnatal day 7-9 ('P7'), bath application of either of the membrane permeable calpain inhibitors, N-Acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLN, 20 μM) or MDL-28170 (30 μM) significantly reduced whole-cell NMDAR current rundown...
May 4, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29778948/bioisosteres-of-ethyl-8-ethynyl-6-pyridin-2-yl-4h-benzo-f-imidazo-1-5-a-1-4-diazepine-3-carboxylate-hz-166-as-novel-alpha-2-3-selective-potentiators-of-gaba-a-receptors-improved-bioavailability-enhances-anticonvulsant-efficacy
#18
J M Witkin, J L Smith, X Ping, S D Gleason, M M Poe, G Li, X Jin, J Hobbs, J M Schkeryantz, J S McDermott, A I Alatorre, J N Siemian, J W Cramer, D C Airey, K R Methuku, V V N P B Tiruveedhula, T M Jones, J Crawford, M J Krambis, J L Fisher, J M Cook, R Cerne
HZ-166 has previously been characterized as an α2,3-selective GABAA receptor modulator with anticonvulsant, anxiolytic, and anti-nociceptive properties but reduced motor effects. We discovered a series of ester bioisosteres with reduced metabolic liabilities, leading to improved efficacy as anxiolytic-like compounds in rats. In the present study, we evaluated the anticonvulsant effects KRM-II-81 across several rodent models. In some models we also evaluated key structural analogs. KRM-II-81 suppressed hyper-excitation in a network of cultured cortical neurons without affecting the basal neuronal activity...
May 3, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29758386/the-neurokinin-1-receptor-mediates-escalated-alcohol-intake-induced-by-multiple-drinking-models
#19
Michelle K Sequeira, Britta S Nelson, Hannah D Fulenwider, Courtney E King, Sadie E Nennig, Jennifer B Bohannon, Kejun Cheng, Kenner C Rice, Markus Heilig, Jesse R Schank
We have previously demonstrated that the neurokinin-1 receptor (NK1R) is upregulated in the central nucleus of the amygdala of alcohol preferring (P) rats and that this receptor mediates escalated alcohol consumption in this strain. However, it is unclear if non-genetic models of escalated consumption are also mediated by NK1R signaling, and if so, what brain regions govern this effect. In the experiments presented here, we use two methods of inducing escalated alcohol intake in outbred Wistar rats: yohimbine pretreatment and intermittent alcohol access (Monday, Wednesday, and Friday availability; 20% alcohol)...
May 3, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29758385/evaluation-of-reinforcing-and-aversive-effects-of-voluntary-%C3%AE-9-tetrahydrocannabinol-ingestion-in-rats
#20
Daniel G Barrus, Timothy W Lefever, Jenny L Wiley
Edible cannabis-infused products are an increasingly popular method of using cannabis in the United States. Yet, preclinical research to determine mechanisms underlying abuse of Δ9 -tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis, has focused primarily on the effects of parenteral administration. The purpose of this study was to examine the rewarding and aversive effects of oral THC in a novel rodent voluntary ingestion model. Adult male and female Sprague Dawley rats were given access to sucrose-sweetened solutions during daily sessions...
May 3, 2018: Neuropharmacology
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