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Neuropharmacology

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https://www.readbyqxmd.com/read/30419245/arrestin-recruitment-and-signaling-by-g-protein-coupled-receptor-heteromers
#1
REVIEW
Kendall L Mores, Robert J Cassell, Richard M van Rijn
G protein-coupled receptors (GPCR) have a long history of being considered a prime target for drug development to treat a plethora of diseases and disorders. In fact in 1827, the first approved therapeutic in the United States was morphine, a drug that targets a GPCR, namely the mu opioid receptor. However, with the rise in biologics over the last two decades, the market share of small molecules targeting GPCRs has declined. Still, two phenomena concerning GPCR pharmacology, specifically heteromerization and biased signaling, have bolstered new interests in this particular class of drug targets...
November 9, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30419244/ethanol-and-a-rapid-acting-antidepressant-produce-overlapping-changes-in-exon-expression-in-the-synaptic-transcriptome
#2
Sarah A Wolfe, Sean P Farris, Joshua E Mayfield, Chelcie F Heaney, Emma K Erickson, R Adron Harris, R Dayne Mayfield, Kimberly F Raab-Graham
Alcohol use disorder (AUD) and major depressive disorder (MDD) are prevalent, debilitating, and highly comorbid disorders. The molecular changes that underlie their comorbidity are beginning to emerge. For example, recent evidence showed that acute ethanol exposure produces rapid antidepressant-like biochemical and behavioral responses. Both ethanol and fast-acting antidepressants block N-methyl-D-aspartate receptor (NMDAR) activity, leading to synaptic changes and long-lasting antidepressant-like behavioral effects...
November 9, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30414871/synergistic-effect-of-aripiprazole-and-escitalopram-in-increasing-serotonin-but-not-norepinephrine-neurotransmission-in-the-rat-hippocampus
#3
Mohammad Ebrahimzadeh, Mostafa El Mansari, Pierre Blier
In addition to schizophrenia and bipolar disorder, aripiprazole is approved as an adjunct for major depressive disorder (MDD). Addition of aripiprazole to the 5-HT reuptake inhibitor escitalopram reverses the inhibitory action of escitalopram on firing activity of rat 5-HT, norepinephrine (NE) and DA neurons. This study investigated how aripiprazole, escitalopram and their combination affect the net effect of 5-HT and NE neurotransmission in the rat hippocampus. Electrophysiological recordings of hippocampus CA3 pyramidal neurons were conducted in anaesthetized Sprague-Dawley rats after 2- and 14-day administration regimens...
November 8, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30408488/heterosynaptic-modulation-in-the-paraventricular-nucleus-of-the-hypothalamus
#4
REVIEW
Julia K Sunstrum, Wataru Inoue
The stress response-originally described by Hans Selye as "the nonspecific response of the body to any demand made upon it"-is chiefly mediated by the hypothalamic-pituitary-adrenal (HPA) axis and is activated by diverse sensory stimuli that inform threats to homeostasis. The diversity of signals regulating the HPA axis is partly achieved by the complexity of afferent inputs that converge at the apex of the HPA axis: this apex is formed by a group of neurosecretory neurons that synthesize corticotropin-releasing hormone (CRH) in the paraventricular nucleus of the hypothalamus (PVN)...
November 5, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30408487/enhancement-of-synaptic-plasticity-and-reversal-of-impairments-in-motor-and-cognitive-functions-in-a-mouse-model-of-angelman-syndrome-by-a-small-neurogenic-molecule-nsi-189
#5
Yan Liu, Karl Johe, Jiandong Sun, Xiaoning Hao, Yubin Wang, Xiaoning Bi, Michel Baudry
NSI-189 Phosphate, (4-benzylpiperazin-1-yl)-[2-(3-methyl-butylamino)pyridin-3-yl] methanone is a new chemical entity under development for the treatment of MDD, based upon preclinical data demonstrating stimulation of neurogenesis of human hippocampus-derived neural stem cells in vitro and in mouse hippocampus in vivo. Previous studies have examined the tolerability and efficacy of NSI-189 for treating major depressive disorder (MDD). NSI-189 has shown significant potential as a treatment for MDD, with concurrent improvement of a cognition scale in a small double-blind, placebo-controlled study...
November 5, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30408486/neuroprotective-action-of-diazepam-at-very-low-and-moderate-doses-in-alzheimer-s-disease-model-rats
#6
Vladimirs Pilipenko, Karina Narbute, Jolanta Pupure, Juris Rumaks, Baiba Jansone, Vija Klusa
Early manifestations of Alzheimer's disease (AD) include neuroinflammation, disrupted neurotransmission and cognitive deficits. Impairment of the GABAergic system is essentially involved in the pathogenesis of AD. Traditionally, agonists of GABAA receptors at doses above 1 mg/kg are known to possess memory impairing effects. However, we have previously found that GABAA receptor GABA site ligand muscimol at very low doses acted contrary - enhanced spatial learning/memory, as well as prevented neuroinflammation and augmented neurotransmission in AD model rats...
November 5, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30408485/therapeutic-impacts-of-environmental-enrichment-neurobiological-mechanisms-informing-molecular-targets-for-enviromimetics
#7
EDITORIAL
Áine Kelly, Anthony J Hannan
No abstract text is available yet for this article.
November 5, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30399367/prosocial-effects-of-an-oxytocin-metabolite-but-not-synthetic-oxytocin-receptor-agonists-in-a-mouse-model-of-autism
#8
Sheryl S Moy, Brian L Teng, Viktoriya D Nikolova, Natallia V Riddick, Catherine D Simpson, Amy Van Deusen, William P Janzen, Maria F Sassano, Cort A Pedersen, Michael B Jarstfer
Currently, there are no established pharmaceutical strategies that effectively treat social deficits in autism spectrum disorder (ASD). Oxytocin, a neurohormone that plays a role in multiple types of social behaviors, has been proposed as a possible therapeutic against social impairment and other symptoms in ASD. However, from the standpoint of pharmacotherapy, oxytocin has several liabilities as a standard clinical treatment, including rapid metabolism, low brain penetrance, and activity at the vasopressin (antidiuretic hormone) receptors...
November 3, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30391731/conditioned-media-from-aicar-treated-skeletal-muscle-cells-increases-neuronal-differentiation-of-adult-neural-progenitor-cells
#9
REVIEW
Hyo Youl Moon, Sahar Javadi, Matthew Stremlau, Kyeong Jin Yoon, Benjamin Becker, Sung-Ung Kang, Xinyu Zhao, Henriette van Praag
Exercise has profound benefits for brain function in animals and humans. In rodents, voluntary wheel running increases the production of new neurons and upregulates neurotrophin levels in the hippocampus, as well as improving synaptic plasticity, memory function and mood. The underlying cellular mechanisms, however, remain unresolved. Recent research indicates that peripheral organs such as skeletal muscle, liver and adipose tissue secrete factors during physical activity that may influence neuronal function...
November 1, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30391505/computation-guided-analysis-of-paroxetine-binding-to-hsert-reveals-functionally-important-structural-elements-and-dynamics
#10
REVIEW
Ara M Abramyan, Rachel D Slack, Sitaram Meena, Bruce A Davis, Amy Hauck Newman, Satinder K Singh, Lei Shi
The serotonin transporter (SERT) is one of the primary targets for medications to treat neuropsychiatric disorders and functions by exploiting pre-existing ion gradients of Na+ , Cl- , and K+ to translocate serotonin from the synaptic cleft into the presynaptic neuron. Although recent hSERT crystal structures represent a milestone for structure-function analyses of mammalian neurotransmitter:sodium symporters, they are all derived from thermostabilized but transport-deficient constructs. Two of these structures are in complex with paroxetine, the most potent selective serotonin reuptake inhibitor known...
October 31, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30385254/s-ketamine-reduces-marble-burying-behaviour-involvement-of-ventromedial-orbitofrontal-cortex-and-ampa-receptors
#11
Cristina Luz Tosta, Gabriela Pandini Silote, Maria Paula Fracalossi, Ariandra Guerini Sartim, Roberto Andreatini, Sâmia Regiane Lourenço Joca, Vanessa Beijamini
Previous clinical and pre-clinical studies suggest the involvement of ventromedial orbitofrontal cortex (vmOFC) and glutamatergic neurotransmission in obsessive-compulsive disorder (OCD). Ketamine, an NMDA glutamatergic receptor antagonist, has shown a rapid and long-lasting antidepressant effect, but its anti-compulsive effect has been scarcely investigated. The antidepressant effect of ketamine involves NMDA receptor blockade, AMPA receptor activation, increased serotonin (5-HT) release and attenuation of nitric oxide (NO) synthesis...
October 29, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30385253/comparison-of-the-behavioral-responses-induced-by-phenylalkylamine-hallucinogens-and-their-tetrahydrobenzodifuran-fly-and-benzodifuran-dragonfly-analogs
#12
Adam L Halberstadt, Muhammad Chatha, Alexander Stratford, Matthias Grill, Simon D Brandt
In recent years, rigid analogues of phenylalkylamine hallucinogens have appeared as recreational drugs. Examples include 2-(8-bromo-2,3,6,7-tetrahydrobenzo[1,2-b:4,5-b']difuran-4-yl)ethan-1-amine (2C-B-FLY) and 1-(8-bromobenzo[1,2-b;4,5-b']difuran-4-yl)-2-aminopropane (Bromo-DragonFLY, DOB-DFLY). Although some rigid compounds such as DOB-DFLY reportedly have higher potency than their non-rigid counterparts, it is not clear whether the same is true for 2C-B-FLY and other tetrahydrobenzodifurans. In the present study, the head twitch response (HTR), a 5-HT2A receptor-mediated behavior induced by serotonergic hallucinogens, was used to assess the effects of 2,5-dimethoxy-4-bromoamphetamine (DOB) and its α-desmethyl homologue 2,5-dimethoxy-4-bromophenethylamine (2C-B), as well as their benzodifuranyl and tetrahydrobenzodifuranyl analogs, in C57BL/6J mice...
October 29, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30393073/targeting-proteoglycan-receptor-ptp%C3%AF-restores-sensory-function-after-spinal-cord-dorsal-root-injury-by-activation-of-erks-creb-signaling-pathway
#13
Min Yao, Haitao Sun, Qiuju Yuan, Ning Li, Heng Li, Yinjuan Tang, Gilberto Kk Leung, Wutian Wu
Dorsal root injury commonly results in irreversible loss of sensory functions because of the limited intrinsic regenerative capacity of adult sensory axons and the growth-inhibitory environment at the dorsal root entry zone (DREZ) between the dorsal root and the spinal cord. Chondroitin sulfate proteoglycans (CSPGs) are the dominant suppressors of axonal regeneration, acting via neuronal receptors including protein tyrosine phosphatase-σ (PTPσ). ISP (Intracellular Sigma Peptide) is a small peptide mimetic of the PTPσ wedge region that has been developed to target PTPσ and relieve CSPG inhibition...
October 28, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30366004/activation-of-trace-amine-associated-receptor-1-attenuates-schedule-induced-polydipsia-in-rats
#14
Ilya Sukhanov, Artem Dorotenko, Antonina Dolgorukova, Marius C Hoener, Raul R Gainetdinov, Anton Yu Bespalov
Trace Amine Associated Receptor 1 (TAAR1) is a novel pharmacological target. TAAR1 are well-documented to play a modulatory role in the dopaminergic system. In spite of a growing number of studies of TAAR1 effects, little is still known about the behavioral pharmacology of TAAR1 ligands, including effects of repeated TAAR1 agonist administration. The present study appears to be the first that estimated the action of TAAR1 agonists on schedule-induced polydipsia, a type of adjunctive behavior, which is considered to be useful for evaluating certain aspects of obsessive-compulsive and related disorders (OCD) and schizophrenia...
October 24, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30366003/apamin-treatment-accelerates-equilibrium-recovery-and-gaze-stabilization-in-unilateral-vestibular-neurectomized-cats-cellular-and-behavioral-aspects
#15
Brahim Tighilet, Jacques Leonard, Christiane Mourre, Christian Chabbert
Sudden and complete unilateral loss of peripheral vestibular inputs evokes characteristic vestibular syndrome comprised of posturo-locomotor, oculomotor, vegetative and cognitive symptoms. Subsequently to the vestibular insult, a neurophysiological process called central vestibular compensation promotes the progressive restoration of the posture and balance. The modulation of the excitability of vestibular secondary neurons has been demonstrated to be a key process of this mechanism. However, the molecular mechanisms that support this modulatory process have thus far not been fully identified...
October 24, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30366002/development-of-the-mam-model-of-schizophrenia-in-mice-sex-similarities-and-differences-of-hippocampal-and-prefrontal-cortical-function
#16
Kleanthi Chalkiadaki, Aggeliki Velli, Evangelos Kyriazidis, Vasiliki Stavroulaki, Vasilis Vouvoutsis, Ekaterini Chatzaki, Michalis Aivaliotis, Kyriaki Sidiropoulou
Schizophrenia is a debilitating disorder with complex and unclarified etiological factors. Sex differences have been observed in humans but animal models have only focused on male subjects. In this study, we report the establishment of the neurodevelopmental MAM model of schizophrenia in mice and compare the schizotypic-like characteristics and cognitive functions in both sexes. Pregnant mice were injected with methylazoxymethanol acetate (MAM) or saline on gestational day (GD) 16 (MAM-16) or 17 (MAM-17). Female MAM-16, but not MAM-17 treated mice exhibited enhanced hyperlocomotion after acute MK-801 administration, compared to saline treated mice...
October 24, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30366005/the-novel-psychoactive-substance-methoxetamine-induces-persistent-behavioral-abnormalities-and-neurotoxicity-in-rats
#17
Giulia Costa, Marcello Serra, Nicholas Pintori, Maria Antonietta Casu, Mary Tresa Zanda, Daniela Murtas, Maria Antonietta De Luca, Nicola Simola, Liana Fattore
Methoxetamine (MXE) is a novel psychoactive substance that can induce several short-term effects on emotional states and behavior. However, little is known about the persistent emotional and behavioral effects of MXE. Moreover, neurotoxic effects of MXE have been hypothesized, but never demonstrated in vivo. To clarify these issues, rats received repeated treatment with MXE every other day (0.1-0.5 mg/kg, i.p., × 5), and 7 days later they were challenged with MXE (0.1-0.5 mg/kg, i.p.). Behavioral effects of MXE were first evaluated by measuring emission of ultrasonic vocalizations and locomotor activity after each administration...
October 23, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30366001/habenula-prefrontal-resting-state-connectivity-in-reactive-aggressive-men-a-pilot-study
#18
REVIEW
G Gan, A Zilverstand, M A Parvaz, R N Preston-Campbell, F d'Oleire Uquillas, S J Moeller, D Tomasi, R Z Goldstein, N Alia-Klein
Disproportionate anger and reactive aggression in response to provocation are core symptoms of intermittent-explosive disorder (IED). Previous research shows a link between the propensity for aggression in healthy individuals and altered functioning of prefrontal-limbic and default-mode networks (DMN) at rest when no provocation is present. In a pilot study, we used resting-state functional magnetic resonance imaging to investigate the effects of pronounced reactive aggression in men, exemplified by IED, on the functional organization of resting-state brain networks including subcortical nodes such as the habenula previously implicated in aggression in preclinical models...
October 23, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30366000/bradykinin-b1-receptor-contributes-to-interleukin-8-production-and-glioblastoma-migration-through-interaction-of-stat3-and-sp-1
#19
Yu-Shu Liu, Jhih-Wen Hsu, Hsiao-Yun Lin, Sheng-Wei Lai, Bor-Ren Huang, Cheng-Fang Tsai, Dah-Yuu Lu
Glioblastoma (GBM), the most aggressive brain tumor, has a poor prognosis due to the ease of migration to surrounding healthy brain tissue. Recent studies have shown that bradykinin receptors are involved in the progression of various cancers. However, the molecular mechanism and pathological role of bradykinin receptors remains unclear. We observed the expressions of two major bradykinin receptors, B1R and B2R, in two different human GBM cell lines, U87 and GBM8901. Cytokine array analysis showed that bradykinin increases the production of interleukin (IL)-8 in GBM via B1R...
October 23, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/30359640/amphetamine-enantiomers-inhibit-homomeric-%C3%AE-7-nicotinic-receptor-through-a-competitive-mechanism-and-within-the-intoxication-levels-in-humans
#20
Daniel R Garton, Sharmaine G Ross, Rafael Maldonado-Hernández, Matthias Quick, José A Lasalde-Dominicci, José E Lizardi-Ortiz
Amphetamine-type stimulants (ATS) are the second most consumed illicit drug worldwide and lack good treatments for associated substance use disorders, lagging behind other addictive drugs. For this reason, a deeper understanding of the pharmacodynamics of ATS is required. The present study seeks to determine amphetamine (AMPH) enantiomers' effects on the homomeric α7 nicotinic acetylcholine receptor (α7 nAChR). Here we have shown that AMPH enantiomers bind to the α7 nAChR and competitively inhibit acetylcholine responses...
October 23, 2018: Neuropharmacology
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