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Neuropharmacology

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https://www.readbyqxmd.com/read/28435008/cortical-and-amygdalar-neuronal-ensembles-in-alcohol-seeking-drinking-and-withdrawal
#1
REVIEW
Olivier George, Bruce T Hope
Alcohol induces many alterations in the brain that are thought to contribute to alcohol addiction. Most of the known alterations are induced in all neurons of a brain area or all neurons of a given cell type, regardless of whether they were activated during behavior. While these alterations can have important modulatory effects on behavior, they cannot explain why animals respond specifically to alcohol-paired cues as opposed to all other non-paired cues, and evoke highly specific goal-directed learned responses in models of drug craving...
April 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28431972/mitochondrial-energy-metabolism-of-rat-hippocampus-after-treatment-with-the-antidepressants-desipramine-and-fluoxetine
#2
Roberto Federico Villa, Federica Ferrari, Laura Bagini, Antonella Gorini, Nicoletta Brunello, Fabio Tascedda
Alterations in mitochondrial functions have been hypothesized to participate in the pathogenesis of depression, because brain bioenergetic abnormalities have been detected in depressed patients by neuroimaging in vivo studies. However, this hypothesis is not clearly demonstrated in experimental studies: some suggest that antidepressants are inhibitors of mitochondrial metabolism, while others observe the opposite. In this study, the effects of 21-day treatment with desipramine (15 mg/kg) and fluoxetine (10 mg/kg) were examined on the energy metabolism of rat hippocampus, evaluating the catalytic activity of regulatory enzymes of mitochondrial energy-yielding metabolic pathways...
April 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28431971/influence-of-stress-associated-with-chronic-alcohol-exposure-on-drinking
#3
REVIEW
Howard C Becker
Stress is commonly regarded as an important trigger for relapse and a significant factor that promotes increased motivation to drink in some individuals. However, the relationship between stress and alcohol is complex, likely changing in form during the transition from early moderated alcohol use to more heavy uncontrolled alcohol intake. A growing body of evidence indicates that prolonged excessive alcohol consumption serves as a potent stressor, producing persistent dysregulation of brain reward and stress systems beyond normal homeostatic limits...
April 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28431970/effects-of-natural-and-synthetic-isothiocyanate-based-h2s-releasers-against-chemotherapy-induced-neuropathic-pain-role-of-kv7-potassium-channels
#4
Lorenzo Di Cesare Mannelli, Elena Lucarini, Laura Micheli, Ilaria Mosca, Paolo Ambrosino, Maria Virginia Soldovieri, Alma Martelli, Lara Testai, Maurizio Taglialatela, Vincenzo Calderone, Carla Ghelardini
Hydrogen sulfide (H2S) is a crucial signaling molecule involved in several physiological and pathological processes. Nonetheless, the role of this gasotransmitter in the pathogenesis and treatment of neuropathic pain is controversial. The aim of the present study was to investigate the pain relieving profile of a series of slow releasing H2S donors (the natural allyl-isothiocyanate and the synthetics phenyl- and carboxyphenyl-isothiocyanate) in animal models of neuropathic pain induced by paclitaxel or oxaliplatin, anticancer drugs characterized by a dose-limiting neurotoxicity...
April 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28431969/crfr1-in-the-ventromedial-caudate-putamen-modulates-acute-stress-enhanced-expression-of-cocaine-locomotor-sensitization
#5
Shuli Liu, Zhiyan Wang, Yijing Li, Xiaowei Sun, Feifei Ge, Mingda Yang, Xinjuan Wang, Na Wang, Junkai Wang, Cailian Cui
Repeated exposure to psychostimulants induces a long-lasting enhancement of locomotor activity called behavioral sensitization, which is often reinforced by stress after drug withdrawal. The mechanisms underlying these phenomena remain elusive. Here we explored the effects of acute stress 3 or 14 days after the cessation of chronic cocaine treatment on the expression of locomotor sensitization induced by a cocaine challenge in rats and the key brain region and molecular mechanism underlying the phenomenon. A single session of forced swimming, as an acute stress (administered 2 days after the cessation of cocaine), significantly enhanced the expression of cocaine locomotor sensitization 14 days after the final cocaine injection (challenge at 12 days after acute stress) but not 3 days after the cessation of cocaine (challenge at 1 day after acute stress)...
April 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28431968/cannabinoid-cb1-and-cb2-receptors-differentially-modulate-l-and-t-type-ca-2-channels-in-rat-retinal-ganglion-cells
#6
Wen-Jing Qian, Ning Yin, Feng Gao, Yanying Miao, Qian Li, Fang Li, Xing-Huai Sun, Xiong-Li Yang, Zhongfeng Wang
Endocannabinoid signaling system is involved in regulating multiple neuronal functions in the central nervous system by activating G-protein coupled cannabinoid CB1 and CB2 receptors (CB1Rs and CB2Rs). Growing evidence has shown that CB1Rs and CB2Rs are extensively expressed in retinal ganglion cells (RGCs). Here, modulation of L- and T-types Ca(2+) channels by activating CB1Rs and CB2Rs in RGCs was investigated. Triple immunofluorescent staining showed that L-type subunit CaV1.2 was co-localized with T-type subunits (CaV3...
April 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28419874/oral-administration-of-a-specific-kynurenic-acid-synthesis-kat-ii-inhibitor-attenuates-evoked-glutamate-release-in-rat-prefrontal-cortex
#7
D M Bortz, H-Q Wu, R Schwarcz, J P Bruno
Cognitive deficits represent core symptoms in schizophrenia (SZ) and predict patient outcome; however, they remain poorly treated by current antipsychotic drugs. Elevated levels of the endogenous alpha7 nicotinic receptor negative allosteric modulator and NMDA receptor antagonist, kynurenic acid (KYNA), are commonly seen in post-mortem tissue and cerebrospinal fluid of patients with SZ. When acutely or chronically elevated in rodents, KYNA produces cognitive deficits similar to those seen in the disease, making down-regulation of KYNA, via inhibition of kynurenine aminotransferase II (KAT II), a potential treatment strategy...
April 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28419873/arrestin-2-and-arrestin-3-differentially-modulate-locomotor-responses-and-sensitization-to-amphetamine
#8
Lilia Zurkovsky, Katayoun Sedaghat, M Rafiuddin Ahmed, Vsevolod V Gurevich, Eugenia V Gurevich
Arrestins play a prominent role in shutting down signaling via G protein-coupled receptors. In recent years, a signaling role for arrestins independent of their function in receptor desensitization has been discovered. Two ubiquitously expressed arrestin isoforms, arrestin-2 and arrestin-3, perform similarly in the desensitization process and share many signaling functions, enabling them to substitute for one another. However, signaling roles specific to each isoform have also been described. Mice lacking arrestin-3 (ARR3KO) were reported to show blunted acute responsiveness to the locomotor stimulatory effect of amphetamine (AMPH)...
April 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28419872/stimulation-of-the-brain-serotonin-receptor-7-rescues-mitochondrial-dysfunction-in-female-mice-from-two-models-of-rett-syndrome
#9
Daniela Valenti, Lidia de Bari, Daniele Vigli, Enza Lacivita, Marcello Leopoldo, Giovanni Laviola, Rosa Anna Vacca, Bianca De Filippis
Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioral and physiological symptoms. Mutations in the methyl CpG binding protein 2 gene (MECP2) cause more than 95% of classic cases, and currently there is no cure for this devastating disorder. Recently we have demonstrated that neurobehavioral and brain molecular alterations can be rescued in a RTT mouse model, by pharmacological stimulation of the brain serotonin receptor 7 (5-HT7R). This member of the serotonin receptor family, crucially involved in the regulation of brain structural plasticity and cognitive processes, can be stimulated by systemic repeated treatment with LP-211, a brain-penetrant selective agonist...
April 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28419871/short-term-inhibition-of-gabaergic-ipscs-induced-by-association-of-pre-and-postsynaptic-activation-in-the-neonatal-hippocampus
#10
Megumi Taketo, Hiroko Matsuda
Activity-dependent plasticity including short and long-term depression accompanied by a reduction in transmitter release probability has been demonstrated in both inhibitory and excitatory synapses. In the neonatal hippocampus, repetitive postsynaptic depolarization is followed by presynaptic alterations of the efficacy of GABAAergic transmission. Both facilitation and inhibition have been observed, but the mechanisms underlying this plasticity have not yet been elucidated. In the present experiment, repetitive postsynaptic depolarization by itself did not cause marked alterations of spontaneous inhibitory postsynaptic currents (sIPSCs)...
April 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28416445/%C3%AE-o-conotoxin-gexiva-disulfide-bond-isomers-exhibit-differential-sensitivity-for-various-nicotinic-acetylcholine-receptors-but-retain-potency-and-selectivity-for-the-human-%C3%AE-9%C3%AE-10-subtype
#11
Dongting Zhangsun, Xiaopeng Zhu, Quentin Kaas, Yong Wu, David J Craik, J Michael McIntosh, Sulan Luo
Nicotinic acetylcholine receptor (nAChR) subtypes exhibit distinct neuropharmacological properties that are involved in a range of neuropathological conditions, including pain, addiction, epilepsy, autism, schizophrenia, Tourette's syndrome, Alzheimer's and Parkinson's diseases, as well as many types of cancer. The α9α10 nAChR is a potential target in chronic pain, wound healing, the pathophysiology of the auditory system, and breast and lung cancers. αO-conotoxin GeXIVA is a potent antagonist of rat α9α10 nAChRs, with the 'bead' disulfide bond isomer displaying the lowest IC50 of the three possible isomers...
April 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28416444/the-pharmacology-of-voltage-gated-sodium-channel-activators
#12
REVIEW
Jennifer R Deuis, Alexander Mueller, Mathilde R Israel, Irina Vetter
Toxins and venom components that target voltage-gated sodium (NaV) channels have evolved numerous times due to the importance of this class of ion channels in the normal physiological function of peripheral and central neurons as well as cardiac and skeletal muscle. NaV channel activators in particular have been isolated from the venom of spiders, wasps, snakes, scorpions, cone snails and sea anemone and are also produced by plants, bacteria and algae. These compounds have provided key insight into the molecular structure, function and pathophysiological roles of NaV channels and are important tools due to their at times exquisite subtype-selectivity...
April 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28416443/astrocytes-modulate-thalamic-sensory-processing-via-mglu2-receptor-activation
#13
C S Copeland, T M Wall, R E Sims, S A Neale, E Nisenbaum, H R Parri, T E Salt
Astrocytes possess many of the same signalling molecules as neurons. However, the role of astrocytes in information processing, if any, is unknown. Using electrophysiological and imaging methods, we report the first evidence that astrocytes modulate neuronal sensory inhibition in the rodent thalamus. We found that mGlu2 receptor activity reduces inhibitory transmission from the thalamic reticular nucleus to the somatosensory ventrobasal thalamus (VB): mIPSC frequencies in VB slices were reduced by the Group II mGlu receptor agonist LY354740, an effect potentiated by mGlu2 positive allosteric modulator (PAM) LY487379 co-application (30 nM LY354740: 10...
April 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28416442/allopregnanolone-decreases-interictal-spiking-and-fast-ripples-in-an-animal-model-of-mesial-temporal-lobe-epilepsy
#14
Maxime Lévesque, Rochelle Herrington, Leila Leclerc, Michael A Rogawski, Massimo Avoli
The objective of this study was to characterize the impact of allopregnanolone, a neurosteroid that acts as a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors, on interictal spikes and high-frequency oscillations (ripples: 80-200 Hz, fast ripples: 250-500 Hz) in the pilocarpine model of mesial temporal lobe epilepsy. Seven out of 25 Sprague-Dawley rats experiencing 1 h of pilocarpine-induced status epilepticus (SE) began treatment with allopregnanolone (9.6-12.8 mg/kg/day) on the following day...
April 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28414051/mechanisms-contributing-to-cognitive-deficits-in-cannabis-users
#15
REVIEW
Romina Mizrahi, Jeremy J Watts, Kuei Y Tseng
Studies from preclinical animal models indicate that sustained activation of CB1 receptor signaling is a major contributing factor for the onset of cognitive deficits associated to chronic cannabis use, in particular within the working memory and decision-making domains. Yet, very few studies have been designed to directly assess the role of CB1 receptors in mediating the effects of cannabis on human brain function. This perspective review article provides an overview of current state of knowledge on possible neurobiological mechanisms accounting for the detrimental effects of chronic cannabis use on cognition and related changes in brain structure and functional connectivity...
April 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28414050/a-study-of-time-and-sex-dependent-effects-of-vortioxetine-on-rat-sexual-behavior-possible-roles-of-direct-receptor-modulation
#16
Yan Li, Alan L Pehrson, Ronald S Oosting, Maria Gulinello, Berend Olivier, Connie Sanchez
Treatment-related sexual dysfunction is a common side effect of antidepressants and contributes to patient non-compliance or treatment cessation. However, the multimodal antidepressant, vortioxetine, demonstrates low sexual side effects in depressed patients. To investigate the mechanisms involved, sexual behavior was assessed in male and female rats after acute, and repeated (7 and 14 days) treatment with vortioxetine, flesinoxan (a 5-HT1A agonist), CP-94253 (a 5-HT1B agonist), or ondansetron (a 5-HT3 antagonist)...
April 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28412320/glibenclamide-ameliorates-cerebral-edema-and-improves-outcomes-in-a-rat-model-of-status-epilepticus
#17
Zhenzhou Lin, Hua Huang, Yong Gu, Kaibin Huang, Yafang Hu, Zhong Ji, Yongming Wu, Shengnan Wang, Tingting Yang, Suyue Pan
Glibenclamide (GBC), a sulfonylurea receptor 1 blocker, emerges recently as a promising neuron protectant in various neurological disorders. This study aimed to determine whether GBC improves survival and neurological outcome of status epilepticus (SE). Male Sprague-Dawley rats successfully undergoing SE for 2.5 h (n = 134) were randomly assigned to GBC or vehicle group. Rats in the GBC group received a loading dose of 10 μg/kg of GBC, followed by 1.2 μg/6 h for 3 days, while same dose of vehicle was used as control...
April 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28408325/developmental-control-of-spike-timing-dependent-plasticity-by-tonic-gabaergic-signaling-in-striatum
#18
Silvana Valtcheva, Vincent Paille, Yulia Dembitskaya, Sylvie Perez, Giuseppe Gangarossa, Elodie Fino, Laurent Venance
Activity-dependent long-term potentiation (LTP) and depression (LTD) of synaptic strength underlie multiple forms of learning and memory. Spike-timing-dependent plasticity (STDP) has been described as a Hebbian synaptic learning rule that could account for experience-dependent changes in neural networks, but little is known about whether and how STDP evolves during development. We previously showed that GABAergic signaling governs STDP polarity and thus operates as a Hebbian/anti-Hebbian switch in the striatum...
April 10, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28400256/n-oleoyldopamine-modulates-activity-of-midbrain-dopaminergic-neurons-through-multiple-mechanisms
#19
Olga A Sergeeva, Roberto De Luca, Karolina Mazur, Aissa N Chepkova, Helmut L Haas, Andreas Bauer
N-oleoyl-dopamine (OLDA) is an amide of dopamine and oleic acid, synthesized in catecholaminergic neurons. The present study investigates OLDA targets in midbrain dopaminergic (DA) neurons. Substantia Nigra compacta (SNc) DA neurons recorded in brain slices were excited by OLDA in wild type mice. In transient receptor potential vanilloid 1 (TRPV1) knockout (KO) mice, however, SNc DA neurons displayed sustained inhibition of firing. In the presence of the dopamine type 2 receptor (D2R) antagonist sulpiride or the dopamine transporter blocker nomifensine no such inhibition was observed...
April 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28400260/prevention-of-the-adverse-effects-of-olanzapine-on-lipid-metabolism-with-the-antiepileptic-zonisamide
#20
Aneta Stefanidis, Matthew J Watt, Michael A Cowley, Brian J Oldfield
BACKGROUND: Atypical antipsychotic drugs, particularly olanzapine, represent a mainstay in the treatment of psychoses; however, their use is commonly associated with weight gain and diabetes. The aim of this study was to determine whether combined administration of olanzapine and zonisamide can be used to prevent olanzapine-induced metabolic disturbances. METHODS AND RESULTS: These experiments involved female Sprague Dawley rats (n = 6-8/group) that were administered olanzapine, either acutely (6 mg/kg, s...
April 8, 2017: Neuropharmacology
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