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Neuropharmacology

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https://www.readbyqxmd.com/read/27914963/hypothermia-in-mouse-is-caused-by-adenosine-a1-and-a3-receptor-agonists-and-amp-via-three-distinct-mechanisms
#1
Jesse Lea Carlin, Shalini Jain, Elizabeth Gizewski, Tina C Wan, Dilip K Tosh, Cuiying Xiao, John A Auchampach, Kenneth A Jacobson, Oksana Gavrilova, Marc L Reitman
Small mammals have the ability to enter torpor, a hypothermic, hypometabolic state, allowing impressive energy conservation. Administration of adenosine or adenosine 5'-monophosphate (AMP) can trigger a hypothermic, torpor-like state. We investigated the mechanisms for hypothermia using telemetric monitoring of body temperature in wild type and receptor knock out (Adora1(-/-)-/-, Adora3(-/-)) mice. Confirming prior data, stimulation of the A3 adenosine receptor (AR) induced hypothermia via peripheral mast cell degranulation, histamine release, and activation of central histamine H1 receptors...
November 30, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27908770/metabotropic-glutamate-receptors-5-years-on
#2
EDITORIAL
Graham Collingridge, Denise Manahan-Vaughan, Ferdinando Nicoletti, Darryle Schoepp
No abstract text is available yet for this article.
November 28, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27908769/chronic-citalopram-administration-desensitizes-prefrontal-cortex-but-not-somatodendritic-%C3%AE-2-adrenoceptors-in-rat-brain
#3
Begoña Fernández-Pastor, Jorge E Ortega, Laura Grandoso, Elena Castro, Luisa Ugedo, Ángel Pazos, J Javier Meana
Selective serotonin reuptake inhibitors (SSRIs) regulate brain noradrenergic neurotransmission both at somatodendritic and nerve terminal areas. Previous studies have demonstrated that noradrenaline (NA) reuptake inhibitors are able to desensitize α2-adrenoceptor-mediated responses. The present study was undertaken to elucidate the effects of repeated treatment with the SSRI citalopram on the α2-adrenoceptor sensitivity in locus coeruleus (LC) and prefrontal cortex (PFC), by using in vivo microdialysis and electrophysiological techniques, and in vitro stimulation of [(35)S]GTPγS binding autoradiography...
November 28, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27908768/acute-stress-diminishes-m-current-contributing-to-elevated-activity-of-hypothalamic-pituitary-adrenal-axis
#4
Jing-Jing Zhou, Yonggang Gao, Therese A Kosten, Zongmao Zhao, De-Pei Li
Acute stress stimulates corticotrophin-releasing hormone (CRH)-expressing neurons in the hypothalamic paraventricular nucleus (PVN), which is an essential component of hypothalamic-pituitary-adrenal (HPA) axis. However, the cellular and molecular mechanisms remain unclear. The M-channel is a voltage-dependent K(+) channel involved in stabilizing the neuronal membrane potential and regulating neuronal excitability. In this study, we tested our hypothesis that acute stress suppresses expression of Kv7 channels to stimulate PVN-CRH neurons and the HPA axis...
November 28, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27899280/behavioural-phenotype-of-histamine-h4-receptor-knockout-mice-focus-on-central-neuronal-functions
#5
Maria Domenica Sanna, Carla Ghelardini, Robin L Thurmond, Emanuela Masini, Nicoletta Galeotti
The functional expression of H4 receptors (H4R) within neurons of the central nervous system has been recently reported, but their role is poorly understood. The present study aims to elucidate the role of neuronal H4R by providing the first description of the behavioural phenotype of H4R-deficient (H4R knockout, H4R-KO) mice. Mice lacking H4R underwent behavioural studies to evaluate locomotor activity, pain perception, anxiety, depression, memory and feeding behaviour. H4R-KO mice showed a significant increase in ambulation in an open field as well as in exploratory activity in the absence of any modification of motor coordination...
November 27, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27899281/sex-differences-in-responses-of-the-basolateral-central-amygdala-circuit-to-alcohol-corticosterone-and-their-interaction
#6
Marian L Logrip, Christopher Oleata, Marisa Roberto
Alcohol use disorders are chronically relapsing conditions that pose significant health challenges for our society. Stress is a prevalent trigger of relapse, particularly for women, yet the mechanisms by which alcohol and stress interact, and how this differs between males and females, remain poorly understood. The glutamatergic circuit connecting the basolateral (BLA) and central (CeA) nuclei of the amygdala is a likely locus for such adaptations, yet the impact of alcohol, corticosterone and their interaction on this circuit has been understudied...
November 26, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27894877/relief-learning-requires-a-coincident-activation-of-dopamine-d1-and-nmda-receptors-within-the-nucleus-accumbens
#7
Jorge R Bergado Acosta, Evelyn Kahl, Georgios Kogias, Taygun C Uzuneser, Markus Fendt
Relief learning is the association of a stimulus with the offset of an aversive event. Later, the now conditioned relief stimulus induces appetitive-like behavioral changes. We previously demonstrated that the NMDA receptors within the nucleus accumbens (NAC) are involved in relief learning. The NAC is also important for reward learning and it has been shown that reward learning is mediated by an interaction of accumbal dopamine and NMDA glutamate receptors. Since conditioned relief has reward-like properties, we hypothesized that (a) acquisition of relief learning requires the activation of dopamine D1 receptors in the NAC, and (b) if D1 receptors are involved in this process as expected, a concurrent dopamine D1 and NMDA receptor activation may mediate this learning...
November 26, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27890603/a-novel-inhibitor-of-endocannabinoid-catabolic-enzymes-sheds-light-on-behind-the-scene-interplay-between-chronic-pain-analgesic-tolerance-and-heroin-dependence
#8
Josée Guindon
From the Aristotelian ancient Greece, pain has been associated with appetites or emotions and is opposite to pleasure. Reward and addiction is also linked to pleasure and compulsive drug seeking reinstates pleasure. Alleviation of chronic pain can induce a euphoric phase similar to what is found in addiction. Both chronic pain and addiction are recognized as a disease of the central nervous system. They share many characteristics and brain regions/mechanisms. Evidence points to the usefulness of cannabinoids as a new class of agents to add to the pharmaceutical toolbox in the management of chronic pain...
November 25, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27890602/the-endocannabinoid-hydrolysis-inhibitor-sa-57-intrinsic-antinociceptive-effects-augmented-morphine-induced-antinociception-and-attenuated-heroin-seeking-behavior-in-mice
#9
Jenny L Wilkerson, Sudeshna Ghosh, Mohammed Mustafa, Rehab A Abdullah, Micah J Niphakis, Roberto Cabrera, Rafael L Maldonado, Benjamin F Cravatt, Aron H Lichtman
Although opioids are highly efficacious analgesics, their abuse potential and other untoward side effects diminish their therapeutic utility. The addition of non-opioid analgesics offers a promising strategy to reduce required antinociceptive opioid doses that concomitantly reduce opioid-related side effects. Inhibitors of the primary endocannabinoid catabolic enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) show opioid-sparing effects in preclinical models of pain. As simultaneous inhibition of these enzymes elicits enhanced antinociceptive effects compared with single enzyme inhibition, the present study tested whether the dual FAAH-MAGL inhibitor SA-57 [4-[2-(4-chlorophenyl)ethyl]-1-piperidinecarboxylic acid 2-(methylamino)-2-oxoethyl ester] produces morphine-sparing antinociceptive effects, without major side effects associated with either drug class...
November 24, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27890601/tramadol-effects-on-sexual-behavior-in-male-rats-are-mainly-caused-by-its-5-ht-reuptake-blocking-effects
#10
Jocelien D A Olivier, Diana C Esquivel Franco, Ronald Oosting, Marcel Waldinger, Zoltan Sarnyai, Berend Olivier
Tramadol is a well-known and effective analgesic. Recently it was shown that tramadol is also effective in human premature ejaculation. The inhibitory effect of tramadol on the ejaculation latency is probably due to its mechanism of action as a μ-opioid receptor agonist and noradrenaline/serotonin (5-HT) reuptake inhibitor. In order to test this speculation, we tested several doses of tramadol in a rat model of male sexual behavior and investigated two types of drugs interfering with the μ-opioid and the 5-HT system...
November 24, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27889491/pramipexole-enhances-disadvantageous-decision-making-lack-of-relation-to-changes-in-phasic-dopamine-release
#11
Romina Pes, Sean C Godar, Andrew T Fox, Lauren M Burgeno, Hunter J Strathman, David P Jarmolowicz, Paola Devoto, Beth Levant, Paul E M Phillips, Stephen C Fowler, Marco Bortolato
Pramipexole (PPX) is a high-affinity D2-like dopamine receptor agonist, used in the treatment of Parkinson's disease (PD) and restless leg syndrome. Recent evidence indicates that PPX increases the risk of problem gambling and impulse-control disorders in vulnerable patients. Although the molecular bases of these complications remain unclear, several authors have theorized that PPX may increase risk propensity by activating presynaptic dopamine receptors in the mesolimbic system, resulting in the reduction of dopamine release in the nucleus accumbens (NAcc)...
November 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27889490/inhibition-of-cathepsin-x-reduces-the-strength-of-microglial-mediated-neuroinflammation
#12
Anja Pišlar, Biljana Božić, Nace Zidar, Janko Kos
Inflammation plays a central role in the processes associated with neurodegeneration. The inflammatory response is mediated by activated microglia that release inflammatory mediators to the neuronal environment. Microglia-derived lysosomal cathepsins, including cathepsin X, are increasingly recognized as important mediators of the inflammation involved in lipopolysaccharide (LPS)-induced neuroinflammation. The current study was undertaken to investigate the role of cathepsin X and its molecular target, γ-enolase, in neuroinflammation and to elucidate the underlying mechanism...
November 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27889489/the-drug-candidate-adx71441-is-a-novel-potent-and-selective-positive-allosteric-modulator-of-the-gabab-receptor-with-a-potential-for-treatment-of-anxiety-pain-and-spasticity
#13
Mikhail Kalinichev, Françoise Girard, Hasnaà Haddouk, Mélanie Rouillier, Eric Riguet, Isabelle Royer-Urios, Vincent Mutel, Robert Lütjens, Sonia Poli
Positive allosteric modulation of the GABAB receptor is a promising alternative to direct activation of the receptor as a therapeutic approach for treatment of addiction, chronic pain, anxiety, epilepsy, autism, Fragile X syndrome, and psychosis. Here we describe in vitro and in vivo characterization of a novel, potent and selective GABAB positive allosteric modulator (PAM) N-(5-(4-(4-chloro-3-fluorobenzyl)-6-methoxy-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)-2-fluorophenyl)acetamide (ADX71441). In vitro, Schild plot and reversibility tests at the target confirmed PAM properties of the compound...
November 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27889488/enhanced-ltp-in-aged-rats-detrimental-or-compensatory
#14
Júlia Pinho, Ruben Vale, Vânia L Batalha, Ana Rita Costenla, Raquel Dias, Diogo Rombo, Ana M Sebastião, Alexandre de Mendonça, Maria José Diógenes
Age-dependent memory deterioration has been well documented and yet an increase in rat hippocampal LTP upon aging has been reported. This poses the question of whether the enhanced LTP is a cause or an attempt to compensate the memory deficits described in aged rats. Hippocampal slices from young, adult and aged Wistar rats were pre-incubated, with an NMDA receptor (NMDAR) antagonist, memantine (1 μM, 4 h), and hippocampal LTP was evaluated. The results show that memantine significantly decreases the larger LTP magnitude recorded in hippocampal slices from aged rats without compromising LTP recorded in slices from young and adult animals...
November 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27876530/two-adjacent-phenylalanines-in-the-nmda-receptor-glun2a-subunit-m3-domain-interactively-regulate-alcohol-sensitivity-and-ion-channel-gating
#15
Hong Ren, Yulin Zhao, Man Wu, Donard S Dwyer, Robert W Peoples
The N-methyl-d-aspartate (NMDA) receptor is a key target of ethanol action in the central nervous system. Alcohol inhibition of NMDA receptor function involves small clusters of residues in the third and fourth membrane-associated (M) domains. Previous results from this laboratory have shown that two adjacent positions in the M3 domain, F636 and F637, can powerfully regulate alcohol sensitivity and ion channel gating. In this study, we report that these positions interact with one another in the regulation of both NMDA receptor gating and alcohol action...
November 19, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27866902/the-atypical-antipsychotic-olanzapine-disturbs-depotentiation-by-modulating-machrs-and-impairs-reversal-learning
#16
Woo Seok Song, Jin Hee Cha, Sang Ho Yoon, Young Seon Cho, Kyeong-Yeol Park, Myoung-Hwan Kim
Antipsychotic medication is an essential component for treating schizophrenia, which is a serious mental disorder that affects approximately 1% of the global population. Olanzapine (Olz), one of the most frequently prescribed atypical antipsychotics, is generally considered a first-line drug for treating schizophrenia. In contrast to psychotic symptoms, the effects of Olz on cognitive symptoms of schizophrenia are still unclear. In addition, the mechanisms by which Olz affects the neural circuits associated with cognitive function are unknown...
November 17, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27856391/acute-anti-allodynic-action-of-gabapentin-in-dorsal-horn-and-primary-somatosensory-cortex-correlation-of-behavioural-and-physiological-data
#17
Sascha R A Alles, Mischa V Bandet, Kate Eppler, Myung-Chul Noh, Ian R Winship, Glen Baker, Klaus Ballanyi, Peter A Smith
Neuropathic pain is a debilitating consequence of neuronal injury or disease. Although first line treatments include the alpha-2-delta (α2δ)-ligands, pregabalin and gabapentin (GBP), the mechanism of their anti-allodynic action is poorly understood. One specific paradox is that GBP relieves signs of neuropathic pain in animal models within 30min of an intraperitoneal (IP) injection yet its actions in vitro on spinal dorsal horn or primary afferent neurons take hours to develop. We found, using confocal Ca(2+) imaging, that substantia gelatinosa neurons obtained ex vivo from rats subjected to sciatic chronic constriction injury (CCI) were more excitable than controls...
November 14, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27847271/oleuropein-improves-mitochondrial-function-to-attenuate-oxidative-stress-by-activating-the-nrf2-pathway-in-the-hypothalamic-paraventricular-nucleus-of-spontaneously-hypertensive-rats
#18
Wenyan Sun, Xin Wang, Chen Hou, Liang Yang, Hongbao Li, Jing Guo, Chanjuan Huo, Molin Wang, Yuwang Miao, Jiankang Liu, Yuming Kang
Hypertension is associated with increased reactive oxygen species (ROS) production in the paraventricular nucleus (PVN) of the hypothalamus. Oleuropein (OL) has a variety of biochemical roles, including antihypertensive and antioxidative functions. However, there have been few reports on the effects of OL on oxidative stress in the PVN on hypertension. In spontaneously hypertensive rats (SHR), eight-week administration of 60 mg/kg/day of OL significantly reduced blood pressure, pro-inflammatory cytokines and the expression of components of the renin-angiotensin system (RAS) compared with SHR rats treated with saline...
November 12, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27845056/antidepressant-like-effects-of-yl-ipa08-a-potent-ligand-for-the-translocator-protein-18%C3%A2-kda-in-chronically-stressed-rats
#19
Li-Ming Zhang, Yu-Lu Wang, Yan-Qin Liu, Rui Xue, You-Zhi Zhang, Ri-Fang Yang, Yun-Feng Li
The present study aimed to examine the molecular and cellular mechanisms underlying the antidepressant-like effect of YL-IPA08, a novel TSPO ligand designed and synthesized at our institute. We firstly used the chronic unpredictable stress (CUS) procedure of rats, a well validated stress-related animal model of depression, to further determine the antidepressant-like of YL-IPA08. And we found that YL-IPA08 caused significant suppression of inhibiting of locomotor activity, reducing the sucrose preference and increasing the latency to eat induced by CUS...
November 11, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27838344/distinct-mechanisms-of-up-state-maintenance-in-the-medial-entorhinal-cortex-and-neocortex
#20
Richard J Digby, Diego S Bravo, Ole Paulsen, Vincent Magloire
The medial entorhinal cortex (mEC) is a key structure which controls the communication between the hippocampus and the neocortex. During slow-wave sleep, it stands out from other cortical regions by exhibiting persistent activity that outlasts neocortical Up states, decoupling the entorhinal cortex-hippocampal interaction from the neocortex. Here, we compared the mechanisms involved in the maintenance of the Up state in the barrel cortex (BC) and mEC using whole cell recordings in acute mouse brain slices. Bath application of an NMDA receptor antagonist abolished Up states in the BC, and reduced the incidence but not the duration of Up states in the mEC...
November 10, 2016: Neuropharmacology
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