Atomoxetine improves memory and other components of executive function in young-adult rats and aged rhesus monkeys.
Abstract Atomoxetine is a norepinephrine reuptake inhibitor and FDA-approved treatment for attention deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults. While there is some evidence that atomoxetine may improve additional domains of cognition beyond attention in both young adults and aged individuals, this subject has not been extensively investigated. Here, we evaluated atomoxetine (in low mg/kg doses) in a variable stimulus duration (vSD) and a variable intertrial interval (vITI) version of the five choice-serial reaction time task (5C-SRTT), and an eight-arm radial arm maze (RAM) procedu...
Source: Neuropharmacology - May 17, 2019 Category: Drugs & Pharmacology Authors: Callahan PM, Plagenhoef MR, Blake DT, Terry AV Tags: Neuropharmacology Source Type: research
Postsynaptic plasticity of GABAergic synapses.
Abstract The flexibility of neuronal networks is believed to rely mainly on the plasticity of excitatory synapses. However, like their excitatory counterparts, inhibitory synapses also undergo several forms of synaptic plasticity. This review examines recent advances in the understanding of the molecular mechanisms leading to postsynaptic GABAergic plasticity. Specifically, modulation of GABAA receptor (GABAAR) number at postsynaptic sites plays a key role, with the interaction of GABAARs with the scaffold protein gephyrin and other postsynaptic scaffold/regulatory proteins having particular importance. Our unders...
Source: Neuropharmacology - May 17, 2019 Category: Drugs & Pharmacology Authors: Barberis A Tags: Neuropharmacology Source Type: research
Structural and molecular aspects of betaine-GABA transporter 1 (BGT1) and its relation to brain function.
rph P Abstract ɣ-aminobutyric-acid (GABA) functions as the principal inhibitory neurotransmitter in the central nervous system. Imbalances in GABAergic neurotransmission are involved in the pathophysiology of various neurological diseases such as epilepsy, Alzheimer's disease and stroke. GABA transporters (GATs) facilitate the termination of GABAergic signaling by transporting GABA together with sodium and chloride from the synaptic cleft into presynaptic neurons and surrounding glial cells. Four different GATs have been identified that all belong to the solute carrier 6 (SLC6) transporter family: GAT1-3 (SLC6A1,...
Source: Neuropharmacology - May 17, 2019 Category: Drugs & Pharmacology Authors: Kickinger S, Hellsberg E, BenteFrølund, Schousboe A, Ecker GF, Wellendorph P Tags: Neuropharmacology Source Type: research
Surface trafficking of neurotransmitter receptors: From cultured neurons to intact brain preparations.
Abstract Over the last decade, developments in single molecule imaging have changed our vision of synaptic physiology. By providing high spatio-temporal resolution maps of the molecular actors of neurotransmissions, these techniques have revealed that pre- and post-synaptic proteins are not randomly distributed but precisely organized at the nanoscale, and that this specific organization is dynamically regulated. At the centre of synaptic transmissions, neurotransmitter receptors have been shown to form nanodomains at synapses and to dynamically move in and out of these confinement areas through lateral diffusion ...
Source: Neuropharmacology - May 17, 2019 Category: Drugs & Pharmacology Authors: Dupuis JP, Groc L Tags: Neuropharmacology Source Type: research
Nano-formulated Curcumin (LipodisqTM) modulates the local inflammatory response, reduces glial scar and preserves the white matter after spinal cord injury in rats.
Abstract A highly water soluble, nano-formulated curcumin was used for the treatment of the experimental model of spinal cord injury (SCI) in rats. Nanocurcumin and a vehicle nanocarrier as a control, were delivered both locally, immediately after the spinal cord injury, and intraperitoneally during the 4 consecutive weeks after SCI. The efficacy of the treatment was assessed using behavioral tests, which were performed during the experiment, weekly for 9 weeks. The behavioral tests (BBB, flat beam test, rotarod, motoRater) revealed a significant improvement in the nanocurcumin treated group, compared to the nanoc...
Source: Neuropharmacology - May 17, 2019 Category: Drugs & Pharmacology Authors: Krupa P, Svobodova B, Dubisova J, Kubinova S, Jendelova P, Urdzikova LM Tags: Neuropharmacology Source Type: research
Memory deficits induced by chronic cannabinoid exposure are prevented by adenosine A2AR receptor antagonism.
Sebastião AM Abstract Patients under cannabis-based therapies are usually chronically exposed to cannabinoids. Chronic treatment with a cannabinoid receptor agonist, WIN 55,212-2, affects brain metabolism and modifies functional connectivity between brain areas responsible for memory and learning. Therefore, it is of uttermost importance to discover strategies to mitigate the negative side-effects of cannabinoid-based therapies. Previously, we showed that a single treatment with the synthetic cannabinoid WIN 55,212-2 disrupts recognition memory, an effect mediated by cannabinoid receptor 1 (CB1R) and cancel...
Source: Neuropharmacology - May 16, 2019 Category: Drugs & Pharmacology Authors: Mouro FM, Köfalvi A, André LA, Baqi Y, Müller CE, Ribeiro JA, Sebastião AM Tags: Neuropharmacology Source Type: research
The protective effects of Ghrelin/GHSR on hippocampal neurogenesis in CUMS mice.
This article shows that ghrelin (5 nmol/kg/day for 2 weeks, i.p.) decreased depression-like behaviors induced by CUMS and increased hippocampal integrity (neurogenesis and spine density) measured via Ki67, 5-bromo-2-deoxyuridine (BrdU), doublecortin (DCX) labeling and Golgi-cox staining, which were decreased under CUMS. The behavioral phenotypes of Growth hormone secretagogue receptor (Ghsr)-null and wild type (WT) mice were evaluated under no stress condition and after CUMS exposure to determine the effect of Ghsr knockout on the behavioral phenotypes and stress susceptibility of mice. Ghsr-null mice exhibited depressio...
Source: Neuropharmacology - May 16, 2019 Category: Drugs & Pharmacology Authors: Huang HJ, Chen XR, Han QQ, Wang J, Pilot A, Yu R, Liu Q, Li B, Wu GC, Wang YQ, Yu J Tags: Neuropharmacology Source Type: research
Role of the endocannabinoid and endovanilloid systems in an animal model of schizophrenia-related emotional processing/cognitive deficit.
io VC Abstract Studies suggest that the endocannabinoid and endovanilloid systems are implicated in the pathophysiology of schizophrenia. The Spontaneously Hypertensive Rats (SHR) strain displays impaired contextual fear conditioning (CFC) attenuated by antipsychotic drugs and worsened by pro-psychotic manipulations. Therefore, SHR strain is used to study emotional processing/associative learning impairments associated with schizophrenia and effects of potential antipsychotic drugs. Here, we evaluated the expression of CB1 and TRPV1 receptors in some brain regions related to the pathophysiology of schizophrenia. W...
Source: Neuropharmacology - May 16, 2019 Category: Drugs & Pharmacology Authors: Almeida V, Levin R, Peres FF, Suiama MA, Vendramini AM, Santos CM, Silva ND, Zuardi AW, Hallak JEC, Crippa JA, Abílio VC Tags: Neuropharmacology Source Type: research
Feedback adaptation of synaptic excitability via Glu:Na+ symport driven astrocytic GABA and Gln release.
cute; Z, Kardos J Abstract Glutamatergic transmission composed of the arriving of action potential at the axon terminal, fast vesicular Glu release, postsynaptic Glu receptor activation, astrocytic Glu clearance and Glu→Gln shuttle is an abundantly investigated phenomenon. Despite its essential role, however, much less is known about the consequences of the mechanistic connotations of Glu:Na+ symport. Due to the coupled Na+ transport, Glu uptake results in significantly elevated intracellular astrocytic [Na+] that markedly alters the driving force of other Na+-coupled astrocytic transporters. The resulting GA...
Source: Neuropharmacology - May 16, 2019 Category: Drugs & Pharmacology Authors: Héja L, Simon Á, Szabó Z, Kardos J Tags: Neuropharmacology Source Type: research
Diversity in the Lateral Hypothalamic input to the Ventral Tegmental Area.
Abstract The obesity epidemic is one of the biggest health challenges globally and rates have tripled since 1975. Overeating is the largest determinant of obesity, yet little is understood of the neural mechanisms underlying why individuals consume food regardless of satiety. The lateral hypothalamic (LH) input to the ventral tegmental area (VTA) has been critically implicated in regulating appetitive and reward-related behaviours. However, these projections are genetically heterogeneous and have different responses to leptin. Therefore each of these projections may play a different role in modulating the VTA. Thi...
Source: Neuropharmacology - May 16, 2019 Category: Drugs & Pharmacology Authors: Godfrey N, Borgland SL Tags: Neuropharmacology Source Type: research
Voluntary wheel running effects on intra-accumbens opioid driven diet preferences in male and female rats.
Abstract Palatability driven feeding and voluntary physical activity are mediated by and influence similar neural mechanisms, notably through the actions of opioids within the nucleus accumbens. Recent studies suggest that access to a voluntary running wheel results in sex dependent behavioral and physiological adaptations related to opioid mediated palatability-driven feeding. To explore this relationship, male and female Wistar rats were given either access to a voluntary running wheel (RUN group) or no access (SED group) for one week prior to being stereotaxically implanted with bilateral cannulae targeting the...
Source: Neuropharmacology - May 14, 2019 Category: Drugs & Pharmacology Authors: Lee JR, Tapia MA, Weise VN, Bathe EL, Vieira-Potter VJ, Booth FW, Will MJ Tags: Neuropharmacology Source Type: research
Corrigendum to "Enhancing endogenous adenosine A2A receptor signaling induces slow-wave sleep without affecting body temperature and cardiovascular function" [Neuropharmacology 144 (2019) 122-132].
Corrigendum to "Enhancing endogenous adenosine A2A receptor signaling induces slow-wave sleep without affecting body temperature and cardiovascular function" [Neuropharmacology 144 (2019) 122-132]. Neuropharmacology. 2019 May 14;: Authors: Korkutata M, Saitoh T, Cherasse Y, Ioka S, Duo F, Qin R, Murakoshi N, Fujii S, Zhou X, Sugiyama F, Chen JF, Kumagai H, Nagase H, Lazarus M PMID: 31101360 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - May 14, 2019 Category: Drugs & Pharmacology Authors: Korkutata M, Saitoh T, Cherasse Y, Ioka S, Duo F, Qin R, Murakoshi N, Fujii S, Zhou X, Sugiyama F, Chen JF, Kumagai H, Nagase H, Lazarus M Tags: Neuropharmacology Source Type: research
Dopamine D2/D3 receptor agonists attenuate PTSD-like symptoms in mice exposed to single prolonged stress.
This study supports the hypothesis that the activation of dopaminergic D2/D3 receptors may be a promising pharmacotherapy for PTSD. PMID: 31085186 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - May 11, 2019 Category: Drugs & Pharmacology Authors: Malikowska-Racia N, Sałat K, Nowaczyk A, Fijałkowski Ł, Popik P Tags: Neuropharmacology Source Type: research
Enhanced aggressive phenotype of Tph2 knockout rats is associated with diminished 5-HT1A receptor sensitivity.
Abstract Brain serotonin (5-HT) plays a key role in aggressive behaviours and related psychopathologies, but its precise mechanism of action remains elusive. Genetic animal models may provide a tool to elucidate the relationship between aggression and serotonin. The present study showed that tryptophan hydroxylase 2 (Tph2) knockout (KO) rats, which exhibit profoundly diminished extracellular serotonin levels, display increased aggressiveness compared to their Tph2 wildtype (WT) counterparts. However, the level of aggression in Tph2 KO rats did not equal that of feral wild type Groningen (WTG) rats. To investigate ...
Source: Neuropharmacology - May 9, 2019 Category: Drugs & Pharmacology Authors: Peeters DGA, Terneusen A, de Boer SF, Newman-Tancredi A, Varney MA, Verkes RJ, Homberg JR Tags: Neuropharmacology Source Type: research
Antipsychotic-evoked dopamine supersensitivity.
Abstract All antipsychotic medications attenuate the symptoms of psychosis by interacting with dopamine D2 receptors and reducing dopamine-mediated neurotransmission. However, long-term antipsychotic treatment can produce neuroadaptations that are thought to lead to dopamine supersensitivity. In patients with schizophrenia, this dopamine supersensitivity could compromise treatment efficacy, promote relapse to psychosis and trigger movement disorders. Such effects have been seen in patients treated with either typical or atypical antipsychotics. In non-human animals, chronic exposure to antipsychotic medications, u...
Source: Neuropharmacology - May 8, 2019 Category: Drugs & Pharmacology Authors: Servonnet A, Samaha AN Tags: Neuropharmacology Source Type: research
Are There Gender Differences in the Response to Antipsychotic Drugs?
CONCLUSION: There is a science, and an art, to prescribing antipsychotics, which needs to take gender into account. PMID: 31077728 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - May 8, 2019 Category: Drugs & Pharmacology Authors: Seeman MV Tags: Neuropharmacology Source Type: research
Insight and medication adherence in schizophrenia: An analysis of the CATIE data.
Abstract Adherence to antipsychotic medication is critical for the treatment of patients with schizophrenia. Impaired insight into illness is one of the principal drivers of medication nonadherence, which contributes to negative clinical outcomes. The aims of this study were to examine the relationships between impaired insight and (1) rates of antipsychotic mediation nonadherence, and (2) time to medication nonadherence using data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). Insight was assessed using the Positive and Negative Syndrome Scale (PANSS) item G12 (lack of judgment and ...
Source: Neuropharmacology - May 8, 2019 Category: Drugs & Pharmacology Authors: Kim J, Ozzoude M, Nakajima S, Shah P, Caravaggio F, Iwata Y, De Luca V, Graff-Guerrero A, Gerretsen P Tags: Neuropharmacology Source Type: research
Insights on current and novel antipsychotic mechanisms from the MAM model of schizophrenia.
Abstract Current antipsychotic drugs (APDs) act on D2 receptors, and preclinical studies demonstrate that repeated D2 antagonist administration downregulates spontaneously active DA neurons by producing overexcitation-induced inactivation of firing (depolarization block). Animal models of schizophrenia based on the gestational MAM administration produces offspring with adult phenotypes consistent with schizophrenia, including ventral hippocampal hyperactivity and a DA neuron overactivity. The MAM model reveals that APDs act differently in a hyperdopamineregic system compared to a normal one, including rapid onset ...
Source: Neuropharmacology - May 8, 2019 Category: Drugs & Pharmacology Authors: Sonnenschein SF, Grace AA Tags: Neuropharmacology Source Type: research
Brain insulin action in schizophrenia: something borrowed and something new.
We describe central nervous system insulin sites and pathways of action, with special emphasis on glucose metabolism, cognitive functioning, inflammation, and food preferences. Finally, we suggest possible mechanisms that may explain the actions of central nervous system insulin in relation to schizophrenia and diabetes, focusing on glutamate and dopamine signaling, intracellular signal transduction pathways, and brain energetics. Understanding the interplay between central nervous system insulin and schizophrenia is essential to disentangling this comorbid relationship and may provide novel treatment approaches for both n...
Source: Neuropharmacology - May 8, 2019 Category: Drugs & Pharmacology Authors: Agarwal SM, Caravaggio F, Costa-Dookhan KA, Castellani L, Kowalchuk C, Asgariroozbehani R, Graff-Guerrero A, Hahn M Tags: Neuropharmacology Source Type: research
Residual avoidance: A new consistent and repeatable readout of chronic stress-induced conflict anxiety reversible by antidepressant treatment.
Abstract Stress-related illnesses such as major depressive and anxiety disorders are characterized by maladaptive responses to stressful life events. Chronic stress-based animal models have provided critical insight into the understanding of these responses. Currently available assays measuring chronic stress-induced behavioral states in mice are limited in their design (short, not repeatable, sensitive to experimenter-bias) and often inconsistent. Using the Noldus PhenoTyper apparatus, we identified a new readout that repeatedly assesses behavioral changes induced by chronic stress in two mouse models i.e. chroni...
Source: Neuropharmacology - May 7, 2019 Category: Drugs & Pharmacology Authors: Prevot TD, Misquitta KA, Fee C, Newton DF, Chatterjee D, Nikolova YS, Sibille E, Banasr M Tags: Neuropharmacology Source Type: research
A loss-of-function mutation of an inhibitory zinc- and proton-binding site reduces channel blocker potency in the glycine receptor.
In this study, we focus on the loss-of-function mutation, H109A, and use the inhibitory potencies of six structurally-diverse channel pore blockers (niflumic acid, picrotoxin, bilobalide, ginkgolide A, ginkgolide B and ginkgolide C) with various molecular volumes to measure the H109A mutation's effect on channel pore conformation. We found that their inhibitory potencies were mostly reduced by the H109A mutation and the extents of reduction were positively correlated with the molecular volumes of the blockers. In addition, we also found that the H109A mutation slowed both the blocking and unblocking rates of the blockers. ...
Source: Neuropharmacology - May 4, 2019 Category: Drugs & Pharmacology Authors: Chen S, Han L, Shan Q Tags: Neuropharmacology Source Type: research
MiR-30b-5p attenuates oxaliplatin-induced peripheral neuropathic pain through the voltage-gated sodium channel Nav1.6 in rats.
Abstract Oxaliplatin is a third-generation derivative of platinum that is effective in the treatment of multiple solid tumors. However, it can cause peripheral neuropathic pain, and the molecular mechanisms of this effect remain unknown. We induced a model of peripheral neuropathic pain in rats by intraperitoneally injecting them with oxaliplatin twice a week for 4.5 weeks. We found that both the mRNA and protein expression levels of Nav1.6 (encoded by the gene Scn8a) increased while the miR-30b-5p (shorthand for miR-30b) expression decreased in the dorsal root ganglion (DRG) of treated rats. Using TargetScan and ...
Source: Neuropharmacology - May 2, 2019 Category: Drugs & Pharmacology Authors: Li L, Shao J, Wang J, Liu Y, Zhang Y, Zhang M, Zhang J, Ren X, Su S, Li Y, Cao J, Zang W Tags: Neuropharmacology Source Type: research
Understanding receptor heteromerization and its allosteric integration of signals.
PMID: 31054939 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - May 2, 2019 Category: Drugs & Pharmacology Authors: Fuxe K, Borroto-Escuela DO Tags: Neuropharmacology Source Type: research
Targeting PSD95-nNOS interaction by Tat-N-dimer peptide during status epilepticus is neuroprotective in MAM-pilocarpine rat model.
Abstract Glutamate receptors play a crucial pathogenic role in brain damage induced by status epilepticus (SE). SE may initiate NMDAR-dependent excitotoxicity through the production of oxidative damage mediated by the activation of a ternary complex formed by the NMDA receptor, the post-synaptic density scaffolding protein 95 (PSD95) and the neuronal NO synthase (nNOS). The inhibition of the protein-protein-interaction (PPI) of the NMDAR-PSD95-nNOS complex is one of the most intriguing challenges recently developed to reduce neuronal death in both animal models and in patients with cerebral ischemia. We took advan...
Source: Neuropharmacology - April 29, 2019 Category: Drugs & Pharmacology Authors: Colciaghi F, Nobili P, Cipelletti B, Cagnoli C, Zambon S, Locatelli D, de Curtis M, Battaglia GS Tags: Neuropharmacology Source Type: research
Glutamate Transport System as a Key Constituent of Glutamosome: Molecular Pathology and Pharmacological Modulation in Chronic Pain.
Abstract Neural uptake of glutamate is executed by the structurally related members of the SLC1A family of solute transporters: GLAST /EAAT1, GLT-1 /EAAT2, EAAC1 /EAAT3, EAAT4, ASCT2. These plasma membrane proteins ensure supply of glutamate, aspartate and some neutral amino acids, including glutamine and cysteine, for synthetic, energetic and signaling purposes, whereas effective removal of glutamate from the synaptic cleft shapes excitatory neurotransmission and prevents glutamate toxicity. Glutamate transporters (GluTs) possess also receptor-like properties and can directly initiate signal transduction. GluTs a...
Source: Neuropharmacology - April 29, 2019 Category: Drugs & Pharmacology Authors: Gegelashvili G, Bjerrum OJ Tags: Neuropharmacology Source Type: research
Probiotic treatment restores normal developmental trajectories of fear memory retention in maternally separated infant rats.
Abstract Early life stress (ELS) can affect brain development and increase lifetime prevalence of psychiatric illnesses. However, the effective therapeutic interventions to ameliorate the deleterious effects of ELS have not yet been well established. Here, we confirmed that maternal separation (MS) for 3 hours daily between postnatal days 2-14, a frequently used experimental model of ELS, resulted in early expression of adult-like fear memory retention in male infant rats. Administration of a probiotic formulation, Lacidofil® (95% Lactobacillus rhamnosus R0011 and 5% Lactobacillus helveticus R0052), during the...
Source: Neuropharmacology - April 26, 2019 Category: Drugs & Pharmacology Authors: Peng HH, Tsai TC, Huang WY, Wu HM, Hsu KS Tags: Neuropharmacology Source Type: research
Null mutation in P4h-tm leads to decreased fear and anxiety and increased social behavior in mice.
In this study, we first investigated the expression pattern of P4H-TM in the mouse brain and found a remarkably selective abundance in brains areas that are involved in social behaviors and anxiety including amygdala, lateral septum and bed nucleus of stria terminalis. Next, we performed behavioral assays in P4h-tm-/- mice to investigate a possible phenotype associated to these brain areas. In locomotor activity tests, we found that P4h-tm-/- mice were significantly more active than their wild-type (WT) littermate mice, and habituation to test environment did not abolish this effect. Instead, spatial learning and memory se...
Source: Neuropharmacology - April 25, 2019 Category: Drugs & Pharmacology Authors: Leinonen H, Koivisto H, Lipponen HR, Matilainen A, Salo AM, Dimova EY, Hämäläinen E, Stavén S, Miettinen P, Myllyharju J, Koivunen P, Tanila H Tags: Neuropharmacology Source Type: research
Combining opioids and non-opioids for pain management: Current status.
Abstract Pain remains a global health challenge. For decades, clinicians have been primarily relying on μ-opioid receptor (MOR) agonists and nonsteroidal anti-inflammatory drugs (NSAIDs) for pain management. MOR agonists remain the most efficacious analgesics available; however, adverse effects related to MOR agonists use are severe which often lead to forced drug discontinuation and inadequate pain relief. The recent opioid overdose epidemic urges the development of safer analgesics. Combination therapy is a well-established clinical pharmacotherapeutic strategy for the treatment of various clinical disorders....
Source: Neuropharmacology - April 25, 2019 Category: Drugs & Pharmacology Authors: Li JX Tags: Neuropharmacology Source Type: research
para-Trifluoromethyl-methcathinone is an allosteric modulator of the serotonin transporter.
HH Abstract The transporters for dopamine (DAT) and serotonin (SERT) are important targets in the treatment of psychiatric disorders including major depression, anxiety and attention-deficit hyperactivity disorder. Drugs acting at these transporters can act as inhibitors or as releasers. In addition, it has been recently appreciated that some compounds are less efficacious releasers than amphetamine. Thus, they are classified as partial releasers. Compounds can act on both SERT and DAT or display exquisite selectivity for either SERT or DAT, but the structural basis for selectivity is poorly understood. The trifl...
Source: Neuropharmacology - April 24, 2019 Category: Drugs & Pharmacology Authors: Niello M, Cintulova D, Hellsberg E, Jäntsch K, Holy M, Ayatollahi LH, Cozzi NV, Freissmuth M, Sandtner W, Ecker GF, Mihovilovic MD, Sitte HH Tags: Neuropharmacology Source Type: research
The antidepressant- and anxiolytic-like effects of resveratrol: Involvement of phosphodiesterase-4D inhibition.
Abstract Resveratrol is a natural non-flavonoid polyphenol found in red wine, which has numerous pharmacological properties including anti-stress and antidepressant-like abilities. However, whether the antidepressant- and anxiolytic-like effects of resveratrol are related to the inhibition of phosphodiesterase 4 (PDE4) and its subtypes remains unknown. The same holds true for the subsequent cAMP-dependent pathway. The first set of studies investigated whether resveratrol exhibited neuroprotective effects against corticosterone-induced cell lesion as well as its underlying mechanism. We found that 100 μM corti...
Source: Neuropharmacology - April 23, 2019 Category: Drugs & Pharmacology Authors: Zhu X, Li W, Li Y, Xu W, Yuan Y, Zheng V, Zhang HT, O'Donnell JM, Xu Y, Yin X Tags: Neuropharmacology Source Type: research
Endocannabinoid Long-Term Depression Revealed at Medial Perforant Path Excitatory Synapses in the Dentate Gyrus.
tie BR, Grandes P Abstract The endocannabinoid system modulates synaptic plasticity in the hippocampus, but a link between long-term synaptic plasticity and the type 1 cannabinoid (CB1) receptor at medial perforant path (MPP) synapses remains elusive. Immuno-electron microscopy in adult mice has shown that ∼26% of the excitatory synaptic terminals in the middle 1/3 of the dentate molecular layer (DML) contain CB1 receptors, and field excitatory postsynaptic potentials evoked by MPP stimulation can be inhibited by CB1 receptor activation. In addition, MPP stimulation at 10 Hz for 10 min triggered CB1 receptor-d...
Source: Neuropharmacology - April 22, 2019 Category: Drugs & Pharmacology Authors: Peñasco S, Rico-Barrio I, Puente N, Gómez-Urquijo SM, Fontaine CJ, Egaña-Huguet J, Achicallende S, Ramos A, Reguero L, Elezgarai I, Nahirney PC, Christie BR, Grandes P Tags: Neuropharmacology Source Type: research
Pharmacological evaluation of clinically relevant concentrations of (2R,6R)-hydroxynorketamine.
Abstract Ketamine is a rapid-onset antidepressant whose efficacy long outlasts its pharmacokinetics. Multiple studies suggest ketamine's antidepressant effects require increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-dependent currents, which have recently been exclusively attributed to its N-methyl-D-aspartate receptor-inactive metabolite (2R,6R)-hydroxynorketamine ((2R,6R)-HNK). To investigate this AMPAR-activation claim further, we estimated and evaluated preclinically and clinically relevant unbound brain HNK concentrations (Cb,u). (2S,6S)-HNK and (2R,6R)-HNK were novelly s...
Source: Neuropharmacology - April 20, 2019 Category: Drugs & Pharmacology Authors: Shaffer CL, Dutra JK, Tseng WC, Weber ML, Bogart LJ, Hales K, Pang J, Volfson D, Am Ende CW, Green ME, Buhl DL Tags: Neuropharmacology Source Type: research
Topical ocular administration of the GLP-1 receptor agonist liraglutide arrests hyperphosphorylated tau-triggered diabetic retinal neurodegeneration via activation of GLP-1R/Akt/GSK3 β signaling.
Topical ocular administration of the GLP-1 receptor agonist liraglutide arrests hyperphosphorylated tau-triggered diabetic retinal neurodegeneration via activation of GLP-1R/Akt/GSK3β signaling. Neuropharmacology. 2019 Apr 20;: Authors: Shu X, Zhang Y, Li M, Huang X, Yang Y, Zeng J, Zhao Y, Wang X, Zhang W, Ying Y Abstract Diabetic retinal neurodegeneration, in particular synaptic neurodegeneration of retinal ganglion cells (RGCs) occurring before RGCs apoptosis, may represent the earliest event in the pathogenesis of diabetic retinopathy (DR). Our previous study identified hyperphosphorylated-ta...
Source: Neuropharmacology - April 20, 2019 Category: Drugs & Pharmacology Authors: Shu X, Zhang Y, Li M, Huang X, Yang Y, Zeng J, Zhao Y, Wang X, Zhang W, Ying Y Tags: Neuropharmacology Source Type: research
Progress in agonist therapy for substance use disorders: Lessons learned from methadone and buprenorphine.
Abstract Substance use disorders (SUD) are serious public health problems worldwide. Although significant progress has been made in understanding the neurobiology of drug reward and the transition to addiction, effective pharmacotherapies for SUD remain limited and a majority of drug users relapse even after a period of treatment. The United States Food and Drug Administration (FDA) has approved several medications for opioid, nicotine, and alcohol use disorders, whereas none are approved for the treatment of cocaine or other psychostimulant use disorders. The medications approved by the FDA for the treatment of S...
Source: Neuropharmacology - April 19, 2019 Category: Drugs & Pharmacology Authors: Jordan CJ, Cao J, Newman AH, Xi ZX Tags: Neuropharmacology Source Type: research
NPC1-deficient neurons are selectively vulnerable for statin treatment.
Abstract Niemann Pick C (NPC) is a fatal hereditary neurovisceral disorder associated with a progressive loss of neurons of unknown mechanism. The disease is caused by mutation in either of two genes, termed npc1 and npc2, accounting for ∼95% and ∼5% of patients, respectively. Recent data suggest a cell-autonomous cause for neuronal cell death. In a former study we could demonstrate that cultured NPC1-deficient (NPC1-/-) neurons are more susceptible to autophagic stress than NPC1-wildtype (wt) neurons. In the present study we tested other stressors for a selective effect on the survival of NPC1-/- neurons....
Source: Neuropharmacology - April 17, 2019 Category: Drugs & Pharmacology Authors: Meske V, Albert F, Gerstenberg S, Kallwellis K, Ohm TG Tags: Neuropharmacology Source Type: research
Roles of K+ and Cation Channels in ORL-1 Receptor-mediated Depression of Neuronal Excitability and Epileptic Activities in the Medial Entorhinal Cortex.
Abstract Nociceptin (NOP) is an endogenous opioid-like peptide that selectively activates the opioid receptor-like (ORL-1) receptors. The entorhinal cortex (EC) is closely related to temporal lobe epilepsy and expresses high densities of ORL-1 receptors. However, the functions of NOP in the EC, especially in modulating the epileptiform activity in the EC, have not been determined. We demonstrated that activation of ORL-1 receptors remarkably inhibited the epileptiform activity in entorhinal slices induced by application of picrotoxin or by deprivation of extracellular Mg2+. NOP-mediated depression of epileptiform ...
Source: Neuropharmacology - April 15, 2019 Category: Drugs & Pharmacology Authors: Li H, Hu B, Zhang HP, Boyle CA, Lei S Tags: Neuropharmacology Source Type: research
Epigenetic regulation of immediate-early gene Nr4a2/Nurr1 in the medial habenula during reinstatement of cocaine-associated behavior.
Abstract Propensity to relapse following long-periods of abstinence is a key feature of substance use disorder. Drugs of abuse, such as cocaine, cause long-term changes in the neural circuitry regulating reward, motivation, and memory processes through dysregulation of various molecular mechanisms, including epigenetic regulation of activity-dependent gene expression. Underlying drug-induced changes to neural circuit function are the molecular mechanisms regulating activity-dependent gene expression. Of note, histone acetyltransferases and histone deacetylases (HDACs), powerful epigenetic regulators of gene expres...
Source: Neuropharmacology - April 15, 2019 Category: Drugs & Pharmacology Authors: Lopez AJ, Hemstedt TJ, Jia Y, Hwang PH, Campbell RR, Kwapis JL, White AO, Chitnis O, Scarfone VM, Matheos DP, Lynch G, Wood MA Tags: Neuropharmacology Source Type: research
Scorpion venom increases acetylcholine release by prolonging the duration of somatic nerve action potentials.
E, Rowan EG Abstract Scorpionism is frequently accompanied by a massive release of catecholamines and acetylcholine from peripheral nerves caused by neurotoxic peptides present in these venoms, which have high specificity and affinity for ion channels. Tityus bahiensis (T. bahiensis) is the second most medically important scorpion species in Brazil but, despite this, its venom remains scarcely studied, especially with regard to its pharmacology on peripheral (somatic and autonomic) nervous system. Here, we evaluated the activity of T. bahiensis venom on somatic neurotransmission using myographic (chick and mouse n...
Source: Neuropharmacology - April 14, 2019 Category: Drugs & Pharmacology Authors: de Cássia O Collaço R, Hyslop S, Dorce VA, Antunes E, Rowan EG Tags: Neuropharmacology Source Type: research
Spinal blockage of CXCL1 and its receptor CXCR2 inhibits paclitaxel-induced peripheral neuropathy in mice.
to JB Abstract Painful peripheral neuropathy is the most dose-limiting side effect of paclitaxel (PTX), a widely used anti-cancer drug to treat solid tumours. The understanding of the mechanisms involved in this side effect is crucial to the development of new therapeutic approaches. CXCL1 chemokine and its receptor CXCR2 have been pointed as promising targets to treat chronic pain. Herein, we sought to evaluate the possible involvement of CXCL1 and CXCR2 in the pathogenesis of PTX-induced neuropathic pain in mice. PTX treatment led to increased levels of CXCL1 in both dorsal root ganglion and spinal cord samples....
Source: Neuropharmacology - April 13, 2019 Category: Drugs & Pharmacology Authors: Manjavachi MN, Passos GF, Trevisan G, Araújo SB, Pontes JP, Fernandes ES, Costa R, Calixto JB Tags: Neuropharmacology Source Type: research
Alpha-lipoic acid alleviated 6-OHDA-induced cell damage by inhibiting AMPK/mTOR mediated autophagy.
In conclusion, ALA alleviated 6-OHDA induced cell injury possibly by inhibiting autophagy mediated by AMPK/mTOR pathway. PMID: 30986422 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - April 12, 2019 Category: Drugs & Pharmacology Authors: Zhou L, Cheng Y Tags: Neuropharmacology Source Type: research
Improvement in inflammation is associated with the protective effect of Gly-Pro-Glu and cycloprolylglycine against A β-induced depletion of the hippocampal somatostatinergic system.
Improvement in inflammation is associated with the protective effect of Gly-Pro-Glu and cycloprolylglycine against Aβ-induced depletion of the hippocampal somatostatinergic system. Neuropharmacology. 2019 Apr 11;: Authors: Aguado-Llera D, Canelles S, Fernández-Mendívil C, Frago LM, Argente J, Arilla-Ferreiro E, López MG, Barrios V Abstract Glycine-proline-glutamate (GPE) is a cleaved tripeptide of IGF-I that can be processed to cycloprolylglycine (cPG) in the brain. IGF-I protects the hippocampal somatostatinergic system from β-amyloid (Aβ) insult and although neith...
Source: Neuropharmacology - April 11, 2019 Category: Drugs & Pharmacology Authors: Aguado-Llera D, Canelles S, Fernández-Mendívil C, Frago LM, Argente J, Arilla-Ferreiro E, López MG, Barrios V Tags: Neuropharmacology Source Type: research
The holy grail of epilepsy prevention: preclinical approaches to antiepileptogenic treatments.
r W Abstract A variety of acute brain insults can induce epileptogenesis, a complex process that results in acquired epilepsy. Despite advances in understanding mechanisms of epileptogenesis, there is currently no approved treatment that prevents the development or progression of epilepsy in patients at risk. The current concept of epileptogenesis assumes a window of opportunity following acute brain insults that allows intervention with preventive treatment. Recent results suggest that injury-induced epileptogenesis can be a much more rapid process than previously thought, suggesting that the 'therapeutic window'...
Source: Neuropharmacology - April 10, 2019 Category: Drugs & Pharmacology Authors: Löscher W Tags: Neuropharmacology Source Type: research
Δ9-tetrahydrocannabinol attenuates oxycodone self-administration under extended access conditions.
This study was conducted to determine if Δ9-tetrahydrocannabinol (THC) enhances the behavioral effects of oxycodone. Male rats were trained to intravenously self-administer (IVSA) oxycodone (0.15 mg/kg/infusion) during 1 h, 4 h or 8 h sessions. Following acquisition rats were exposed to THC by vapor inhalation (1 h and 8 h groups) or injection (0-10 mg/kg, i.p.; all groups) prior to IVSA sessions. Fewer oxycodone infusions were obtained by rats following vaporized or injected THC compared with vehicle treatment prior to the session. Follow-up studies demonstrated parallel dose-dependent effects of THC, ...
Source: Neuropharmacology - April 10, 2019 Category: Drugs & Pharmacology Authors: Nguyen JD, Grant Y, Creehan KM, Hwang CS, Vandewater SA, Janda KD, Cole M, Taffe MA Tags: Neuropharmacology Source Type: research
The highly selective dopamine D3R antagonist, RVK4-40, attenuates oxycodone reward and augments analgesia in rodents.
Abstract Prescription opioid abuse is a global crisis. New treatment strategies for pain and opioid use disorders are urgently required. We evaluated the effects of RVK4-40, a highly selective dopamine (DA) D3 receptor (D3R) antagonist, on the rewarding and analgesic effects of oxycodone, the most commonly abused prescription opioid, in rats and mice. Systemic administration of RVK4-40 dose-dependently inhibited oxycodone self-administration and shifted oxycodone dose-response curves downward in rats. Pretreatment with RVK4-40 also dose-dependently lowered break-points for oxycodone under a progressive-ratio sched...
Source: Neuropharmacology - April 8, 2019 Category: Drugs & Pharmacology Authors: Jordan CJ, Humburg B, Rice M, Bi GH, You ZB, Shaik AB, Cao J, Bonifazi A, Gadiano A, Rais R, Slusher B, Newman AH, Xi ZX Tags: Neuropharmacology Source Type: research
The bivalent ligand MCC22 potently attenuates hyperalgesia in a mouse model of cisplatin-evoked neuropathic pain without tolerance or reward.
DA Abstract Cisplatin and other widely employed platinum-based anticancer agents produce chemotherapy-induced peripheral neuropathy (CIPN) that often results in pain and hyperalgesia that are difficult to manage. We investigated the efficacy of a novel bivalent ligand, MCC22, for the treatment of pain arising from CIPN. MCC22 consists of mu opioid receptor (MOR) agonist and chemokine receptor 5 (CCR5) antagonist pharmacophores connected through a 22-atom spacer and was designed to target a putative MOR-CCR5 heteromer localized in pain processing areas. Mice received once daily intraperitoneal (i.p.) injections of...
Source: Neuropharmacology - April 7, 2019 Category: Drugs & Pharmacology Authors: Cataldo G, Erb SJ, Lunzer MM, Luong N, Akgün E, Portoghese PS, Olson JK, Simone DA Tags: Neuropharmacology Source Type: research
Evidence for nonlinear accumulation of the ultrapotent fentanyl analog, carfentanil, after systemic administration to male rats.
Abstract The current opioid overdose crisis is being exacerbated by illicitly manufactured fentanyl and its analogs. Carfentanil is a fentanyl analog that is 10,000-times more potent than morphine, but limited information is available about its pharmacology. The present study had two aims: 1) to validate a method for quantifying carfentanil and its metabolite norcarfentanil in small-volume samples, and 2) to use the method for examining pharmacodynamic-pharmacokinetic relationships in rats. The analytical method involved liquid-liquid extraction of plasma samples followed by quantitation of carfentanil and norcarf...
Source: Neuropharmacology - April 6, 2019 Category: Drugs & Pharmacology Authors: Skov-Skov Bergh M, Bogen IL, Garibay N, Baumann MH Tags: Neuropharmacology Source Type: research
Temporal development of behavioral impairments in rats following locus coeruleus lesion induced by 6-hydroxydopamine: involvement of β3-adrenergic receptors.
Temporal development of behavioral impairments in rats following locus coeruleus lesion induced by 6-hydroxydopamine: involvement of β3-adrenergic receptors. Neuropharmacology. 2019 Apr 05;: Authors: Sampaio TB, Soares de Souza B, Roversi K, Schuh T, Poli A, Takahashi RN, Prediger RD Abstract Noradrenergic degeneration in the locus coeruleus (LC) seems a convergent neuropathological marker of different neurodegenerative diseases. Herein, we investigated the temporal development of apoptotic signaling activation in the LC, noradrenergic dysfunction and behavioral impairments in rats following the ...
Source: Neuropharmacology - April 5, 2019 Category: Drugs & Pharmacology Authors: Sampaio TB, Soares de Souza B, Roversi K, Schuh T, Poli A, Takahashi RN, Prediger RD Tags: Neuropharmacology Source Type: research
The novel dehydroepiandrosterone (DHEA) derivative BNN27 counteracts behavioural deficits induced by the NMDA receptor antagonist ketamine in rats.
Abstract Consistent experimental evidence supports an important role of the glutamatergic system in the etiopathogenesis of schizophrenia. Numerous studies propose that blockade of the NMDA receptor by its antagonist ketamine impairs cognition and can mimic certain aspects of positive and negative symptoms of schizophrenia in rodents. Neuroactive steroids, including dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) were shown to affect brain glutamatergic system and to be implicated in schizophrenia. BNN27 is a novel DHEA derivative, which is devoid of steroidogenic activity. The neuroprote...
Source: Neuropharmacology - April 5, 2019 Category: Drugs & Pharmacology Authors: Zoupa E, Gravanis A, Pitsikas N Tags: Neuropharmacology Source Type: research
Perinatal fluoxetine exposure changes social and stress-coping behavior in adult rats housed in a seminatural environment.
Abstract The use of selective serotonin reuptake inhibitors (SSRI) during pregnancy has increased tremendously, but the consequences for the offspring remain largely unclear. Several studies have described potential effects of perinatal SSRI-exposure on neurobehavioral outcomes using simplified rodent test set-ups, however these set-ups only assess a small fraction of the behavior. For translational purposes it is important to take the environmental influences into account which children are exposed to in real life. By using a seminatural environmental set-up, this study is the first to assess behavioral outcomes ...
Source: Neuropharmacology - April 5, 2019 Category: Drugs & Pharmacology Authors: Houwing DJ, Heijkoop R, Olivier JDA, Snoeren EMS Tags: Neuropharmacology Source Type: research
Teamwork: ion channels and transporters join forces in the brain.
Abstract Voltage-gated potassium (Kv) channels open in response to changes in membrane potential to permit passage of K+ ions across the cell membrane, down their electrochemical gradient. Sodium-coupled solute transporters utilize the downhill sodium gradient to co-transport solutes, ranging from ions to sugars to neurotransmitters, into the cell. A variety of recent studies have uncovered cooperation between these two structurally and functionally unrelated classes of protein, revealing previously unnoticed functional crosstalk and in many cases physical interaction to form channel-transporter (chansporter) comp...
Source: Neuropharmacology - April 5, 2019 Category: Drugs & Pharmacology Authors: Manville RW, Abbott GW Tags: Neuropharmacology Source Type: research