Neuronal preservation and reactive gliosis attenuation following neonatal sciatic nerve axotomy by a fluorinated cannabidiol derivative.
This study shows that use of the fluorinated synthetic version of CBD (4'-fluoro-cannabidiol, HUF-101) significantly improves neuronal survival by 2-fold compared to that achieved with traditional CBD at one-third the dose. Furthermore, we show that HUF-101 administration significantly upregulates anti-apoptotic genes and blocks the expression of pro-apoptotic nuclear factors. Two-day-old Wistar rats were subjected to unilateral sectioning of the sciatic nerve and treated daily with HUF-101 (1, 2.5, 5 mg/kg/day, i.p.) or a vehicle solution for five days. The results were evaluated by Nissl staining, immunohistochemistry, a...
Source: Neuropharmacology - August 7, 2018 Category: Drugs & Pharmacology Authors: Perez M, Cartarozzi LP, Chiarotto GB, Alves de Oliveira S, Guimarães FS, Rodrigues de Oliveira AL Tags: Neuropharmacology Source Type: research

Regulation of P2X7 receptor function of neural progenitor cells in the hippocampal subgranular zone by neuronal activity in the dentate gyrus.
Abstract P2X7 receptors (Rs) mediate apoptosis/necrosis in neuronal and non-neuronal systems. Patch-clamp recordings from dentate gyrus (DG) granule cells in acutely prepared hippocampal slices of mice showed that incubation with 4-aminopyridine (4-AP) causes an excitability increase. This led to an enhanced sensitivity of P2X7Rs of the underlying subgranular zone neural progenitor cells (NPCs) towards dibenzoyl-ATP (Bz-ATP). The glutamatergic agonists NMDA and AMPA, as well as the purinergic agonist ATP also increased the Bz-ATP-induced current amplitudes (IBzATP). Tetrodotoxin as well as the standard antiepilept...
Source: Neuropharmacology - August 6, 2018 Category: Drugs & Pharmacology Authors: Khan MT, Liu J, Nerlich J, Tang Y, Franke H, Illes P Tags: Neuropharmacology Source Type: research

A single cocaine administration alters dendritic spine morphology and impairs glutamate receptor synaptic retention in the medial prefrontal cortex of adolescent rats.
Abstract The brain is still maturing during adolescence and interfering with such a vulnerable period may lead to structural and functional consequences. We investigated the effect of a single cocaine exposure on dendritic spine structure and glutamate dynamics in the medial prefrontal cortex (mPFC) of adolescent rats 7 days after a single cocaine administration. We found a reduced number of dendritic spines, suggesting that cocaine lowers the density of dendritic spines in the mPFC of adolescent rats. Since dendritic spines are postsynaptic glutamatergic protrusions, we investigated the main determinants of gluta...
Source: Neuropharmacology - August 6, 2018 Category: Drugs & Pharmacology Authors: Caffino L, Messa G, Fumagalli F Tags: Neuropharmacology Source Type: research

Pathophysiology and treatment of cerebral edema in traumatic brain injury.
Abstract Cerebral edema (CE) and resultant intracranial hypertension are associated with unfavorable prognosis in traumatic brain injury (TBI). CE is a leading cause of in-hospital mortality, occurring in>60% of patients with mass lesions, and ∼15% of those with normal initial computed tomography scans. After treatment of mass lesions in severe TBI, an important focus of acute neurocritical care is evaluating and managing the secondary injury process of CE and resultant intracranial hypertension. This review focuses on a contemporary understanding of various pathophysiologic pathways contributing to CE, wit...
Source: Neuropharmacology - August 4, 2018 Category: Drugs & Pharmacology Authors: Jha RM, Kochanek PM, Simard JM Tags: Neuropharmacology Source Type: research

Role of PPAR- β/δ/miR-17/TXNIP pathway in neuronal apoptosis after neonatal hypoxic-ischemic injury in rats.
Role of PPAR-β/δ/miR-17/TXNIP pathway in neuronal apoptosis after neonatal hypoxic-ischemic injury in rats. Neuropharmacology. 2018 Aug 04;: Authors: Gamdzyk M, Doycheva DM, Malaguit J, Enkhjargal B, Tang J, Zhang JH Abstract Activation of peroxisome proliferator-activated receptor beta/delta (PPAR-β/δ), a nuclear receptor acting as a transcription factor, was shown to be protective in various models of neurological diseases. However, there is no information about the role of PPAR-β/δ as well as its molecular mechanisms in neonatal hypoxia-ischemia (HI). In the present...
Source: Neuropharmacology - August 4, 2018 Category: Drugs & Pharmacology Authors: Gamdzyk M, Doycheva DM, Malaguit J, Enkhjargal B, Tang J, Zhang JH Tags: Neuropharmacology Source Type: research

Modulation of appetitive motivation by prefrontal cortical mu-opioid receptors is dependent upon local dopamine D1 receptor signaling.
Abstract Opioid neurotransmission has been implicated in psychiatric disorders featuring impaired inhibitory control over appetitive motivation, such as addiction and binge-eating disorder. We have previously shown that infusions of the μ-opioid receptor (μOR) agonist DAMGO into the ventromedial prefrontal cortex (vmPFC) induced hyperphagia, increased motor activity, and augmented sucrose-reinforced responding in the task progressive ratio (PR) task, which assesses the motivational value of an incentive. These effects were not reproduced by intra-PFC infusion of a variety of dopamine (DA) agonists and antago...
Source: Neuropharmacology - August 4, 2018 Category: Drugs & Pharmacology Authors: Selleck RA, Giacomini J, Buchholtz BD, Lake C, Sadeghian K, Baldo BA Tags: Neuropharmacology Source Type: research

Newer Pharmacological Approaches for Antioxidant Neuroprotection in Traumatic Brain Injury.
Abstract Reactive oxygen species-induced oxidative damage remains an extensively validated secondary injury mechanism in traumatic brain injury (TBI) as demonstrated by the efficacy of various pharmacological antioxidants agents in decreasing post-traumatic free radical-induced lipid peroxidation (LP) and protein oxidative damage in preclinical TBI models. Based upon strong preclinical efficacy results, two antioxidant agents, the superoxide radical scavenger polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) and the 21-aminosteroid LP inhibitor tirilazad, which inhibits lipid peroxidation, (LP) were ev...
Source: Neuropharmacology - August 4, 2018 Category: Drugs & Pharmacology Authors: Hall ED, Wang JA, Miller DM, Cebak JE, Hill RL Tags: Neuropharmacology Source Type: research

The novel, catalytic mTORC1/2 inhibitor PQR620 and the PI3K/mTORC1/2 inhibitor PQR530 effectively cross the blood-brain barrier and increase seizure threshold in a mouse model of chronic epilepsy.
uml;scher W Abstract The mTOR signaling pathway has emerged as a possible therapeutic target for epilepsy. Clinical trials have shown that mTOR inhibitors such as everolimus reduce seizures in tuberous sclerosis complex patients with intractable epilepsy. Furthermore, accumulating preclinical data suggest that mTOR inhibitors may have anti-seizure or anti-epileptogenic actions in other types of epilepsy. However, the chronic use of rapalogs such as everolimus is limited by poor tolerability, particularly by immunosuppression, poor brain penetration and induction of feedback loops which might contribute to their li...
Source: Neuropharmacology - August 3, 2018 Category: Drugs & Pharmacology Authors: Brandt C, Hillmann P, Noack A, Römermann K, Öhler LA, Rageot D, Beaufils F, Melone A, Sele AM, Wymann MP, Fabbro D, Löscher W Tags: Neuropharmacology Source Type: research

Role of Toll-like receptor mediated signaling in traumatic brain injury.
Abstract The mechanisms underlying secondary brain damage following traumatic brain injury (TBI) remain unclear. A great many studies have demonstrated that inflammatory cascades contribute to brain damage through the activation of immune/inflammatory responses, including the increased release of cytokines and chemokines, and the recruitment of leukocytes. The cells and tissues damaged by primary mechanical injury release a number of endogenous factors acting as damage-associated molecular patterns (DAMPs), which initiate and perpetuate noninfectious inflammatory responses through transduction signaling pathways. ...
Source: Neuropharmacology - July 31, 2018 Category: Drugs & Pharmacology Authors: Shi H, Hua X, Kong D, Stein D, Hua F Tags: Neuropharmacology Source Type: research

Maladaptive behavioral regulation in alcohol dependence: Role of kappa-opioid receptors in the bed nucleus of the stria terminalis.
Abstract There is an important emerging role for the endogenous opioid dynorphin (DYN) and the kappa-opioid receptor (KOR) in the treatment of alcohol dependence. Evidence suggests a role for the DYN/KOR system in the bed nucleus of the stria terminalis (BNST) in maladaptive behavioral regulation related to alcohol dependence and withdrawal. The current experiments were designed to assess dysregulation of the BNST DYN/KOR system by evaluating alcohol dependence-induced changes in DYN/KOR gene expression (Pdyn and Oprk1, respectively), and the sensitivity of alcohol self-administration, negative affective-like beha...
Source: Neuropharmacology - July 31, 2018 Category: Drugs & Pharmacology Authors: Erikson CM, Wei G, Walker BM Tags: Neuropharmacology Source Type: research

Potential role of the ecto-5'-nucleotidase in morphine-induced uridine release and neurobehavioral changes.
Abstract There is growing evidence that uridine may act as an endogenous neuromodulator with a potential signaling role in the central nervous system in addition to its function in pyrimidine metabolism. We previously found that acute morphine treatment significantly increased uridine release in the dorsal striatum of mice, indicating that uridine may contribute to morphine-induced neurobehavioral changes. In the present study, we analyzed the mechanism involved in morphine-induced uridine release and the role of uridine in morphine-induced neurobehavioral changes. Uridine release in the dorsal striatum of mice wa...
Source: Neuropharmacology - July 30, 2018 Category: Drugs & Pharmacology Authors: Che X, Liu P, Wu C, Song W, An N, Yu L, Bai Y, Xing Z, Cai J, Wang X, Yang J Tags: Neuropharmacology Source Type: research

Pharmacological modulation of colorectal distension evoked potentials in conscious rats.
n L Abstract BACKGROUND: Cerebral evoked potentials (CEP) induced by colorectal distension (CRD) in conscious rats provides a novel method in studies of visceral sensitivity. The aim of this study was to explore the pharmacological effect on CEP of compounds known to reduce the visceromotor response to CRD. METHODS: Epidural electrodes were chronically implanted in eight female Sprague-Dawley rats. Evoked potentials were elicited by colorectal rapid balloon distensions (100 ms, 80 mmHg) and the effect of WIN55 (cannabinoid CB receptor agonist), clonidine (adrenergic α2 receptor agonist), MPEP (mGluR...
Source: Neuropharmacology - July 27, 2018 Category: Drugs & Pharmacology Authors: Nissen TD, Brock C, Lykkesfeldt J, Lindström E, Hultin L Tags: Neuropharmacology Source Type: research

Increasing Brain-Derived Neurotrophic Factor (BDNF) in medial prefrontal cortex selectively reduces excessive drinking in ethanol dependent mice.
Abstract The neurotrophin Brain-Derived Neurotrophic Factor (BDNF) has been implicated in a number of neuropsychiatric disorders, including alcohol use disorder. Studies have shown that BDNF activity in cortical regions, such as the medial prefrontal cortex (mPFC) mediates various ethanol-related behaviors. We previously reported a significant down-regulation in Bdnf mRNA in mPFC following chronic ethanol exposure compared to control mice. The present study was conducted to extend these findings by examining whether chronic ethanol treatment reduces BDNF protein expression in mPFC and whether reversing this defici...
Source: Neuropharmacology - July 26, 2018 Category: Drugs & Pharmacology Authors: Haun HL, Griffin WC, Lopez MF, Solomon MG, Mulholland PJ, Woodward JJ, McGinty JF, Ron D, Becker HC Tags: Neuropharmacology Source Type: research

Chronic treatment with the phytocannabinoid Cannabidivarin (CBDV) rescues behavioural alterations and brain atrophy in a mouse model of Rett syndrome.
Abstract Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioural and physiological symptoms. RTT is caused by mutations in the MECP2 gene in about 95% of cases and to date no cure is available. The endocannabinoid system modulates several physiological processes and behavioural responses that are impaired in RTT and its deregulation has been associated with neuropsychiatric disorders which have symptoms in common with RTT. The present study evaluated the potential therapeutic efficacy for RTT of cannabidivarin (CBDV), a non-psychotropic phytocannabinoid from Cannabis sativa t...
Source: Neuropharmacology - July 26, 2018 Category: Drugs & Pharmacology Authors: Vigli D, Cosentino L, Raggi C, Laviola G, Woolley-Roberts M, De Filippis B Tags: Neuropharmacology Source Type: research

Abnormalities in behaviour, histology and prefrontal cortical gene expression profiles relevant to schizophrenia in embryonic day 17 MAM-Exposed C57BL/6 mice.
Abstract Gestational and perinatal disruption of neural development increases the risk of developing schizophrenia (SCZ) later in life. Embryonic day 17 (E17) methylazoxymethanol (MAM) treatment leads to histological, physiological and behavioural abnormalities in post-puberty rats that model the neuropathological and cognitive deficits reported in SCZ patients. However, the validity of E17 MAM-exposed mice to model SCZ has not been explored. Here we treated E17 C57BL/6 mouse dams with various dosages of MAM. We found that this mouse strain was more vulnerable to MAM treatment than rats and there were gender diffe...
Source: Neuropharmacology - July 26, 2018 Category: Drugs & Pharmacology Authors: Huo C, Liu X, Zhao J, Zhao T, Huang H, Ye H Tags: Neuropharmacology Source Type: research

Interplay between 5-HT2C and 5-HT1A receptors in the dorsal periaqueductal gray in the modulation of fear-induced antinociception in mice.
Abstract The confinement of rodents to the open arm of the elevated-plus maze provokes antinociception (OAA). As a type of defensive reaction, the OAA has been investigated through systemic and intramesencephalic (e.g., dorsal portion of the periaqueductal gray - dPAG) injections of anxiolytic-like drugs [e.g., serotonergic (5-HT) receptor agonists or antagonists]. Here we investigated the effects of (i) intra-dPAG injections of a 5HT2C receptor agonist (MK-212; 0.21 or 0.63 nmol) and antagonist (SB 242084; 0.01, 0.1 or 1.0 nmol); (ii) combined injections of SB 242084 and MK-212 into the dPAG; (iii) combined injec...
Source: Neuropharmacology - July 26, 2018 Category: Drugs & Pharmacology Authors: Baptista-de-Souza D, Pelarin V, Canto-de-Souza L, Nunes-de-Souza RL, Canto-de-Souza A Tags: Neuropharmacology Source Type: research

Targeting the TREK-1 potassium channel via riluzole to eliminate the neuropathic and depressive-like effects of oxaliplatin.
Abstract Neurotoxicity remains the most common adverse effect of oxaliplatin, limiting its clinical use. In the present study, we developed a mouse model of chronic oxaliplatin-induced neuropathy, which mimics both sensory and motor deficits observed in patients, in a clinically relevant time course. Repeated oxaliplatin administration in mice induced both cephalic and extracephalic long lasting mechanical and cold hypersensitivity after the first injection as well as delayed sensorimotor deficits and a depression-like phenotype. Using this model, we report that riluzole prevents both sensory and motor deficits in...
Source: Neuropharmacology - July 26, 2018 Category: Drugs & Pharmacology Authors: Poupon L, Lamoine S, Pereira V, Barriere DA, Lolignier S, Giraudet F, Aissouni Y, Meleine M, Prival L, Richard D, Kerckhove N, Authier N, Balayssac D, Eschalier A, Lazdunski M, Busserolles J Tags: Neuropharmacology Source Type: research

Persistent effect of withdrawal from intravenous methamphetamine self-administration on brain activation and behavioral economic indices involving an effort cost.
Abstract Exposure to drugs of abuse produces maladaptive changes in cost-benefit decision-making, including the evaluation of time and risk. Studies probing the effects of drug exposure on such evaluations have primarily used experimenter-administered drug regimens. Similarly, while much is known about the neural bases of effort, there have been relatively fewer investigations of the effects of drug experience on effort-based choices. We recently reported that experimenter-administered methamphetamine (meth) resulted in steeper discounting of effort for food rewards in rats, when assessed in protracted withdrawal....
Source: Neuropharmacology - July 24, 2018 Category: Drugs & Pharmacology Authors: Hart EE, Gerson JO, Izquierdo A Tags: Neuropharmacology Source Type: research

Maternal methamphetamine exposure causes cognitive impairment and alteration of neurodevelopment-related genes in adult offspring mice.
Abstract Prenatal drug exposure altered cognitive function in individuals, and may also impact their offspring's susceptibility to cognitive impairment. The high incidence of methamphetamine (METH) abuse among adolescents and women of childbearing age elevates the importance to determine the influence of maternal METH exposure on cognitive functions in the descendants. We hypothesized that maternal METH exposure affects cognitive behavior in offspring mice by disrupting gene expression associated with neural development. Here, female C57BL/6 mice were exposed to intermittent escalating doses of METH or saline from...
Source: Neuropharmacology - July 23, 2018 Category: Drugs & Pharmacology Authors: Dong N, Zhu J, Han W, Wang S, Yan Z, Ma D, Goh ELK, Chen T Tags: Neuropharmacology Source Type: research

Naltrexone and Nalmefene Attenuate Cocaine Place Preference in Male Mice.
CONCLUSION: Both NTX and NMF block the place preference, but not locomotor activating, effects of cocaine. These results suggest that both NTX and NMF may be viable pharmacotheraputics for some aspects of cocaine addiction. This is an important step to understanding the potential mechanism(s) of action of NTX and NMF for the development of more efficacious pharmacological treatments for substance use disorders. PMID: 30048644 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - July 23, 2018 Category: Drugs & Pharmacology Authors: Windisch KA, Reed B, Kreek MJ Tags: Neuropharmacology Source Type: research

Evaluation of alcohol use disorders pharmacotherapies in a new preclinical model of binge drinking.
Naassila M Abstract Binge drinking is defined as a pattern of drinking leading to intoxication in a single short session and is a serious but preventable public health problem. Only few animal models of voluntary binge drinking using an operant paradigm are available in outbred animals and in general they do not display good face validity. We recently set up a new model of binge drinking behavior using an operant self-administration paradigm in which rats drink to intoxication level in 15-min daily session. Here we tested the current pharmacotherapies of alcohol use disorder: Acamprosate, (R)-Baclofen, gamma-hydr...
Source: Neuropharmacology - July 18, 2018 Category: Drugs & Pharmacology Authors: González-Marín MC, Lebourgeois S, Jeanblanc J, Diouf M, Naassila M Tags: Neuropharmacology Source Type: research

Cannabinoid type 2 receptors mediate a cell type-specific self-inhibition in cortical neurons.
Abstract Endogenous cannabinoids are diffusible lipid ligands of the main cannabinoid receptors type 1 and 2 (CB1R and CB2R). In the central nervous system endocannabinoids are produced in an activity-dependent manner and have been identified as retrograde modulators of synaptic transmission. Additionally, some neurons display a cell-autonomous slow self-inhibition (SSI) mediated by endocannabinoids. In these neurons, repetitive action potential firing triggers the production of endocannabinoids, which induce a long-lasting hyperpolarization of the membrane potential, rendering the cells less excitable. Different ...
Source: Neuropharmacology - July 16, 2018 Category: Drugs & Pharmacology Authors: Stumpf A, Parthier D, Sammons RP, Stempel AV, Breustedt J, Rost BR, Schmitz D Tags: Neuropharmacology Source Type: research

Species specificity of rat and human α7 nicotinic acetylcholine receptors towards different classes of peptide and protein antagonists.
Species specificity of rat and human α7 nicotinic acetylcholine receptors towards different classes of peptide and protein antagonists. Neuropharmacology. 2018 Jul 16;: Authors: Yu J, Zhu X, Zhang L, Kudryavtsev D, Kasheverov I, Lei Y, Zhangsun D, Tsetlin V, Luo S Abstract Peptide and protein neurotoxins, such as α-conotoxins from Cone snails and α-neurotoxins from snake venoms, are excellent tools to identify distinct nicotinic acetylcholine receptor (nAChR) subtypes. Here we compared the rat/human species specificity of α7 nAChR towards peptide and protein neurotoxins and fou...
Source: Neuropharmacology - July 16, 2018 Category: Drugs & Pharmacology Authors: Yu J, Zhu X, Zhang L, Kudryavtsev D, Kasheverov I, Lei Y, Zhangsun D, Tsetlin V, Luo S Tags: Neuropharmacology Source Type: research

The α6 subunit-containing GABAA receptor: A novel drug target for inhibition of trigeminal activation.
We examined effects of these compounds on both central and peripheral TGVS responses induced by i.c. capsaicin. Compound 6 (3-10 mg/kg, i.p.) significantly attenuated the TCC neuronal activation and TG CGRP-ir elevation, and dural CGRP depletion induced by capsaicin. All these effects of Compound 6 were mimicked by topiramate, Ro15-4513 and loreclezole, but not by diazepam. The brain-impermeable furosemide antagonized the peripheral, but not central, effects of Compound 6. These results suggest that the α6GABAAR in TG is a novel drug target for TGVS activation and that α6GABAAR-selective PAMs have the potenti...
Source: Neuropharmacology - July 14, 2018 Category: Drugs & Pharmacology Authors: Fan PC, Lai TH, Hor CC, Lee MT, Huang P, Sieghart W, Ernst M, Knutson DE, Cook J, Chiou LC Tags: Neuropharmacology Source Type: research

Prenatal stress leads to synaptic remodeling and excessive alcohol intake comorbid with anxiety-like behaviors in adult offspring.
Abstract Currently, the etiology of anxiety comorbid with alcohol use disorder (AUD) remains to be elucidated. Epidemiologic evidence suggests that individuals during their prenatal development may be especially vulnerable to the effects of environmental factors such as stress that predisposes them to psychiatric disorders including AUD later in life. To explore the cause of the comorbidity, we examined anxiety-like and alcohol drinking behaviors in adult offspring of prenatally stressed dam (referred as PRS-mice) using well-characterized paradigms-elevated plus maze (EPM), light/dark box (LDB) and two-bottle free...
Source: Neuropharmacology - July 14, 2018 Category: Drugs & Pharmacology Authors: Dong E, Guidotti A, Zhang H, Pandey SC Tags: Neuropharmacology Source Type: research

The NMDA receptor antagonist Radiprodil reverses the synaptotoxic effects of different amyloid-beta (A β) species on long-term potentiation (LTP).
In this study we show that different β-amyloid species, 1-42 Aβ1-42 and 1-40 (Aβ1-40) as well as post-translationally modified forms such as pyroglutamate-modified amyloid-(AβpE3) and nitrated Aβ (3NTyr10-Aβ), when applied for 90 min to murine hippocampal slices, concentration-dependently prevented the development of CA1-LTP after tetanic stimulation of the Schaffer collaterals with IC50s of 2, 9, 2 and 35 nM, respectively whilst having no effect on baseline AMPA receptor mediated fEPSPs. Aβ1-43 had no effect. Interestingly, the combination of all Aβ species did not result in any...
Source: Neuropharmacology - July 14, 2018 Category: Drugs & Pharmacology Authors: Rammes G, Seeser F, Mattusch K, Zhu K, Haas L, Kummer M, Heneka M, Herms J, Parsons CG Tags: Neuropharmacology Source Type: research

Contributions of medial prefrontal cortex to decision making involving risk of punishment.
Abstract The prefrontal cortex (PFC) plays an important role in several forms of cost-benefit decision making. Its contributions to decision making under risk of explicit punishment, however, are not well understood. A rat model was used to investigate the role of the medial PFC (mPFC) and its monoaminergic innervation in a Risky Decision-making Task (RDT), in which rats chose between a small, "safe" food reward and a large, "risky" food reward accompanied by varying probabilities of mild footshock punishment. Inactivation of mPFC increased choice of the large, risky reward when the punishment ...
Source: Neuropharmacology - July 13, 2018 Category: Drugs & Pharmacology Authors: Orsini CA, Heshmati SC, Garman TS, Wall SC, Bizon JL, Setlow B Tags: Neuropharmacology Source Type: research

Anti-cancer and analgesic effects of resolvin D2 in oral squamous cell carcinoma.
dt BL Abstract Oral cancer is often painful and lethal. Oral cancer progression and pain may result from shared pathways that involve unresolved inflammation and elevated levels of pro-inflammatory cytokines. Resolvin D-series (RvDs) are endogenous lipid mediators derived from omega-3 fatty acids that exhibit pro-resolution and anti-inflammatory actions. These mediators have recently emerged as a novel class of therapeutics for diseases that involve inflammation; the specific roles of RvDs in oral cancer and associated pain are not defined. The present study investigated the potential of RvDs (RvD1 and RvD2) to tr...
Source: Neuropharmacology - July 12, 2018 Category: Drugs & Pharmacology Authors: Ye Y, Scheff NN, Bernabé D, Salvo E, Ono K, Liu C, Veeramachaneni R, Viet CT, Viet DT, Dolan JC, Schmidt BL Tags: Neuropharmacology Source Type: research

Identification by virtual screening and functional characterisation of novel positive and negative allosteric modulators of the α7 nicotinic acetylcholine receptor.
Identification by virtual screening and functional characterisation of novel positive and negative allosteric modulators of the α7 nicotinic acetylcholine receptor. Neuropharmacology. 2018 Jul 12;: Authors: Smelt CLC, Sanders VR, Newcombe J, Burt RP, Sheppard TD, Topf M, Millar NS Abstract Several previous studies have demonstrated that the activity of neurotransmitters acting on ligand-gated ion channels such as the nicotinic acetylcholine receptor (nAChR) can be altered by compounds binding to allosteric modulatory sites. In the case of α7 nAChRs, both positive and negative allosteric mo...
Source: Neuropharmacology - July 12, 2018 Category: Drugs & Pharmacology Authors: Smelt CLC, Sanders VR, Newcombe J, Burt RP, Sheppard TD, Topf M, Millar NS Tags: Neuropharmacology Source Type: research

Aiming for the Target: Mitochondrial Drug Delivery in Traumatic Brain Injury.
Abstract Mitochondria are a keystone of neuronal function, serving a dual role as sustainer of life and harbinger of death. While mitochondria are indispensable for energy production, a dysregulated mitochondrial network can spell doom for both neurons and the functions they provide. Traumatic brain injury (TBI) is a complex and biphasic injury, often affecting children and young adults. The primary pathological mechanism of TBI is mechanical, too rapid to be mitigated by anything but prevention. However, the secondary injury of TBI evolves over hours and days after the initial insult providing a window of opportu...
Source: Neuropharmacology - July 12, 2018 Category: Drugs & Pharmacology Authors: Lamade AM, Kenny EM, Anthonymuthu TS, Soysal E, Clark R, Kagan VE, Bayır H Tags: Neuropharmacology Source Type: research

5-HT1A receptor-mediated activation of neuroendocrine responses and multiple protein kinase pathways in the peripubertal rat hypothalamus.
This study provides the first demonstration of functional 5-HT1A receptor-mediated ERK and Akt signaling pathways in the immature hypothalamus, activated by a dose of (+)8-OH-DPAT that concomitantly stimulates neuroendocrine responses. This information is fundamental to identifying potential signaling pathways targeted by biased agonists in the development of safe and effective treatment strategies in children and adolescents. PMID: 30005975 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - July 10, 2018 Category: Drugs & Pharmacology Authors: Petrunich-Rutherford ML, Garcia F, Battaglia G Tags: Neuropharmacology Source Type: research

Investigating the role of mGluR2 versus mGluR3 in antipsychotic-like effects, sleep-wake architecture and network oscillatory activity using novel Han Wistar rats lacking mGluR2 expression.
Abstract Group II metabotropic glutamate receptors (mGluR2 and mGluR3) are implicated in a number of psychiatric disorders. They also control sleep-wake architecture and may offer novel therapeutic targets. However, the roles of the mGluR2 versus mGluR3 subtypes are not well understood. Here, we have taken advantage of the recently described mutant strain of Han Wistar rats, which do not express mGluR2 receptors, to investigate behavioural, sleep and EEG responses to mGluR2/3 ligands. The mGluR2/3 agonist, LY354740 (10 mg/kg), reversed amphetamine- and phencyclidine-induced locomotion and rearing behaviours in c...
Source: Neuropharmacology - July 10, 2018 Category: Drugs & Pharmacology Authors: Wood CM, Wafford KA, McCarthy AP, Hewes N, Shanks E, Lodge D, Robinson ES Tags: Neuropharmacology Source Type: research

Methylene blue activates the PMCA activity and cross-interacts with amyloid β-peptide, blocking Aβ-mediated PMCA inhibition.
Methylene blue activates the PMCA activity and cross-interacts with amyloid β-peptide, blocking Aβ-mediated PMCA inhibition. Neuropharmacology. 2018 Jul 09;: Authors: Berrocal M, Corbacho I, Gutierrez-Merino C, Mata AM Abstract The phenothiazine methylene blue (MB) is attracting increasing attention because it seems to have beneficial effects in the pathogenesis of Alzheimer's disease (AD). Among other factors, the presence of neuritic plaques of amyloid-β peptide (Aβ) aggregates, neurofibrilar tangles of tau and perturbation of cytosolic Ca2+ are important players of the disease. ...
Source: Neuropharmacology - July 9, 2018 Category: Drugs & Pharmacology Authors: Berrocal M, Corbacho I, Gutierrez-Merino C, Mata AM Tags: Neuropharmacology Source Type: research

Methotrexate causes persistent deficits in memory and executive function in a juvenile animal model.
In conclusion, our study demonstrated that a clinically relevant regimen of systemic and intrathecal methotrexate induces persistent deficits in spatial pattern memory, visual recognition memory and executive function, lasting at least 8 weeks after the last injection. The mechanisms behind methotrexate-induced deficits are likely multifactorial and may relate to suppression of neurogenesis, alterations in neuroinflammation and microglial activation, and structural changes in the corpus callosum. PMID: 29990472 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - July 7, 2018 Category: Drugs & Pharmacology Authors: Wen J, Maxwell RR, Wolf AJ, Spira M, Gulinello ME, Cole PD Tags: Neuropharmacology Source Type: research

Melanin-concentrating hormone and orexin systems in nucleus incertus: Dual innervation, bidirectional effects on neuron activity, and differential influences on arousal and feeding.
Abstract The rat nucleus incertus (NI) contains GABA/peptide-projection neurons responsive to orexin (hypocretin)/orexin receptor-2 (OX2) signalling. Melanin-concentrating hormone (MCH) and orexin neurons often innervate and influence common target areas. Therefore, we assessed the relationship between these hypothalamic peptidergic systems and rat NI, by investigating the presence of an MCH innervation and MCH receptor-1 (MCH1) expression, and neurophysiological and behavioural effects of MCH c.f. orexin-A (OXA), within the NI. We identified lateral hypothalamus (LH), perifornical and sub-zona incerta MCH neurons...
Source: Neuropharmacology - July 5, 2018 Category: Drugs & Pharmacology Authors: Sabetghadam A, Grabowiecka-Nowak A, Kania A, Gugula A, Blasiak E, Blasiak T, Ma S, Gundlach AL, Blasiak A Tags: Neuropharmacology Source Type: research

Thioredoxin-1 downregulation in nucleus accumbens promotes methamphetamine-primed reinstatement in mice.
Abstract Relapse of drug abuse after abstinence is a major challenge to the treatment of addicts. Thioredoxin-1 (Trx-1) is an important regulator of neuroprotection, and inhibits morphine-induced hyperlocomotion, reward and withdrawal signs, as well as blocks methamphetamine (METH)-induced conditioned place preference (CPP). Nucleus accumbens (NAc) is essential for relapse like behavior in reinstatement animal models. In the present study, we aim to investigate the role of Trx-1 in NAc in METH-primed reinstatement by using a reinstatement procedure in mice. Adeno-associated virus vectors expressing shRNA-mTrx-1 (A...
Source: Neuropharmacology - July 4, 2018 Category: Drugs & Pharmacology Authors: Huang M, Yan C, Yang X, Zhou X, Lv W, Guo N, Li Y, Bai J Tags: Neuropharmacology Source Type: research

Synthetic peripherally-restricted cannabinoid suppresses chemotherapy-induced peripheral neuropathy pain symptoms by CB1 receptor activation.
Abstract Chemotherapy-induced peripheral neuropathy (CIPN) is a severe and dose-limiting side effect of cancer treatment that affects millions of cancer survivors throughout the world and current treatment options are extremely limited by their side effects. Cannabinoids are highly effective in suppressing pain symptoms of chemotherapy-induced and other peripheral neuropathies but their widespread use is limited by central nervous system (CNS)-mediated side effects. Here, we tested one compound from a series of recently developed synthetic peripherally restricted cannabinoids (PRCBs) in a rat model of cisplatin-in...
Source: Neuropharmacology - July 4, 2018 Category: Drugs & Pharmacology Authors: Mulpuri Y, Marty VN, Munier JJ, Mackie K, Schmidt BL, Seltzman HH, Spigelman I Tags: Neuropharmacology Source Type: research

The highly selective 5-HT2A antagonist EMD-281,014 reduces dyskinesia and psychosis in the L-DOPA-treated parkinsonian marmoset.
Abstract Blockade of serotonin 2A (5-HT2A) receptors is regarded as an anti-dyskinetic and anti-psychotic strategy in Parkinson's disease (PD). However, the 5-HT2A antagonists tested so far exhibited affinity for other receptors, which might have played a role in their action. EMD-281,014 is the most selective 5-HT2A antagonist available, with approximately 2,000-fold selectivity over serotonin 2C (5-HT2C) receptors. EMD-281,014 was previously tested in the clinic and has high translational potential. In the present study, we assessed the effect of EMD-281,014 on dyskinesia and psychosis in the 1-methyl-4-phenyl-1...
Source: Neuropharmacology - June 30, 2018 Category: Drugs & Pharmacology Authors: Hamadjida A, Nuara SG, Bedard D, Gaudette F, Beaudry F, Gourdon JC, Huot P Tags: Neuropharmacology Source Type: research

Positive psychology in the investigation of psychedelics and entactogens: A critical review.
CONCLUSIONS: There is preliminary evidence for beneficial effects of psychedelics and entactogens on measures of positive psychology in clinical and healthy populations, however their sustainability remains largely unresolved. The reported results must be considered preliminary due to methodological restrictions. Since longitudinal data on both positive and adverse effects of psychedelics are lacking, more rigorous and standardized measures from positive psychology should be applied in less biased populations with prospective longitudinal designs to carefully assess the benefit-risk-ratio. PMID: 29964094 [PubMed - as ...
Source: Neuropharmacology - June 29, 2018 Category: Drugs & Pharmacology Authors: Jungaberle H, Thal S, Zeuch A, Rougemont-Bücking A, von Heyden M, Aicher H, Scheidegger M Tags: Neuropharmacology Source Type: research

Cocaine-induced epigenetic DNA modification in mouse addiction-specific and non-specific tissues.
Abstract Cocaine-related DNA methylation studies have primarily focused on the specific brain regions associated with drug addiction (e.g., the nucleus accumbens, NAc). To date, no studies have focused on the complex role of both DNA methylation and demethylation in the mechanisms of psychostimulant-induced addiction in the brain and peripheral tissues. Therefore, in this study, we evaluated cocaine treatment and withdrawal (animals were withdrawn from seven days of repeated injections of cocaine that caused behavioral sensitization) effects on epigenetic DNA modifiers (i.e., DNA methyltransferases, [DNMTs] and te...
Source: Neuropharmacology - June 28, 2018 Category: Drugs & Pharmacology Authors: Anier K, Urb M, Kipper K, Herodes K, Timmusk T, Zharkovsky A, Kalda A Tags: Neuropharmacology Source Type: research

Exposure to environmental enrichment attenuates addiction-like behavior and alters molecular effects of heroin self-administration in rats.
This study examined the impact of environmental enrichment on heroin self-administration, addiction-related behaviors, and molecular processes proposed to underlie these behaviors. Male Sprague-Dawley rats in standard and enriched housing conditions intravenously self-administered similar amounts of heroin over 14 days. However, environmental enrichment attenuated progressive ratio, extinction, and reinstatement session responding after 14 days of enforced abstinence. Molecular mechanisms, namely DNA methylation and gene expression, are proposed to underlie abstinence-persistent behaviors. A global reduction in methylation...
Source: Neuropharmacology - June 28, 2018 Category: Drugs & Pharmacology Authors: Imperio CG, McFalls AJ, Hadad N, Blanco-Berdugo L, Masser DR, Colechio EM, Coffey AA, Bixler GV, Stanford DR, Vrana KE, Grigson PS, Freeman WM Tags: Neuropharmacology Source Type: research

Group I metabotropic glutamate receptors generate two types of intrinsic membrane oscillations in hippocampal oriens/alveus interneurons.
Abstract GABAergic interneurons in the hippocampus are critically involved in almost all hippocampal circuit functions including coordinated network activity. Somatostatin-expressing oriens-lacunosum moleculare (O-LM) interneurons are a major subtype of dendritically projecting interneurons in hippocampal subregions (e.g., CA1), and express group I metabotropic glutamate receptors (mGluRs), specifically mGluR1 and mGluR5. Group I mGluRs are thought to regulate hippocampal circuit functions partially through GABAergic interneurons. Previous studies suggest that a group I/II mGluR agonist produces slow supra-thresho...
Source: Neuropharmacology - June 28, 2018 Category: Drugs & Pharmacology Authors: Govindaiah G, Kang YJ, Smashey Lewis HE, Chung L, Clement EM, Greenfield LJ, Garcia-Rill E, Lee SH Tags: Neuropharmacology Source Type: research

Chronic stress dysregulates amygdalar output to the prefrontal cortex.
Abstract Chronic stress contributes to the neuropathology of mental health disorders, including those associated with anxiety. The basolateral amygdala (BLA) coordinates emotional behavioral responses through glutamatergic outputs to downstream regions such as the prefrontal cortex (PFC), nucleus accumbens core (NAcc) and bed nucleus of the stria terminalis (BNST). We explored the effects of chronic stress on BLA outputs to the PFC, NAcc and BNST using slice electrophysiology combined with optogenetics in two inbred mouse strains with distinct stress-induced anxiety responses. We found that ten consecutive days of...
Source: Neuropharmacology - June 27, 2018 Category: Drugs & Pharmacology Authors: Lowery-Gionta EG, Crowley NA, Bukalo O, Silverstein S, Holmes A, Kash TL Tags: Neuropharmacology Source Type: research

(2R,6R)-hydroxynorketamine rescues chronic stress-induced depression-like behavior through its actions in the midbrain periaqueductal gray.
Abstract It has been widely reported that ketamine rescues chronic stress-induced depression-like behavior, but the underlying cellular mechanisms of the rapid antidepressant actions of ketamine remain largely unclear. Both male and female Sprague-Dawley rats were used and received modified learned helplessness paradigm to induce depression-like behavior. Depression-like behavior was assayed and manipulated using forced swim tests, sucrose preference tests and pharmacological microinjection. We conducted whole-cell patch-clamp electrophysiological recordings in the midbrain ventrolateral periaqueductal gray (vlPAG...
Source: Neuropharmacology - June 25, 2018 Category: Drugs & Pharmacology Authors: Chou D, Peng HY, Lin TB, Lai CY, Hsieh MC, Wen YC, Lee AS, Wang HH, Yang PS, Chen GD, Ho YC Tags: Neuropharmacology Source Type: research

Synaptic modification by L-theanine, a natural constituent in green tea, rescues the impairment of hippocampal long-term potentiation and memory in AD mice.
Abstract Synaptic refinement improves synaptic efficiency, which provides a possibility to improve memory in Alzheimer's disease (AD). In the current study, we aimed to investigate the role of L-theanine, a natural constituent in green tea, in hippocampal synaptic transmission and to assess its potential to improve memory in transgenic AD mice. Initially, we found that L-theanine bath application facilitated hippocampal synaptic transmission and reduced paired-pulse facilitation (PPF). These effects were blocked by antagonists of N-methyl-D-aspartic acid receptors and the dopamine D1/5 receptor, and a selective pr...
Source: Neuropharmacology - June 23, 2018 Category: Drugs & Pharmacology Authors: Zhu G, Yang S, Xie Z, Wan X Tags: Neuropharmacology Source Type: research

Knockout of alpha 5 nicotinic acetylcholine receptors subunit alters ethanol-mediated behavioral effects and reward in mice.
Abstract Evidence suggests that there is an association between polymorphisms in the α5 nicotinic acetylcholine receptor (nAChR) subunit and risk of developing alcohol dependence in humans. The α5 nAChR subunit has also recently been shown to modulate some of the acute response to ethanol in mice. The aim of the current study was to further characterize the role of α5-containing (α5*) nAChRs in acute ethanol responsive behaviors, ethanol consumption and ethanol preference in mice. We conducted a battery of tests in male α5 knockout (KO) mice for a range of ethanol-induced behaviors in...
Source: Neuropharmacology - June 23, 2018 Category: Drugs & Pharmacology Authors: Dawson A, Wolstenholme JT, Roni MA, Campbell VC, Jackson A, Slater C, Bagdas D, Perez EE, Bettinger JC, De Biasi M, Miles MF, Damaj MI Tags: Neuropharmacology Source Type: research

Serotonergic mechanisms involved in antidepressant-like responses evoked by GLT-1 blockade in rat infralimbic cortex.
as F, Castañé A Abstract Novel fast-acting antidepressant strategies, such as ketamine and deep brain stimulation, enhance glutamatergic neurotransmission in medial prefrontal cortex (mPFC) regions via AMPA receptor (AMPA-R) activation. We recently reported that the regionally-selective blockade of the glial glutamate transporter-1 (GLT-1) by dihydrokainic acid (DHK) microinfusion in rat infralimbic cortex (IL), the most ventral part of the mPFC, evoked immediate (10 min) antidepressant-like responses, which involved AMPA-R activation and were associated to increased serotonin (5-hydroxytryptamine,...
Source: Neuropharmacology - June 22, 2018 Category: Drugs & Pharmacology Authors: Gasull-Camós J, Martínez-Torres S, Tarrés-Gatius M, Ozaita A, Artigas F, Castañé A Tags: Neuropharmacology Source Type: research

Attenuated dopaminergic neurodegeneration and motor dysfunction in hemiparkinsonian mice lacking the α5 nicotinic acetylcholine receptor subunit.
Attenuated dopaminergic neurodegeneration and motor dysfunction in hemiparkinsonian mice lacking the α5 nicotinic acetylcholine receptor subunit. Neuropharmacology. 2018 Jun 22;: Authors: Leino S, Koski SK, Hänninen R, Tapanainen T, Rannanpää S, Salminen O Abstract Preclinical studies suggest the involvement of various subtypes of nicotinic acetylcholine receptors in the pathophysiology of Parkinson's disease, a neurodegenerative disorder characterized by the death of dopaminergic neurons in the substantia nigra pars compacta (SNC). We studied for the first time the effects of &al...
Source: Neuropharmacology - June 22, 2018 Category: Drugs & Pharmacology Authors: Leino S, Koski SK, Hänninen R, Tapanainen T, Rannanpää S, Salminen O Tags: Neuropharmacology Source Type: research

Inhibition of non-NMDA ionotropic glutamate receptors delays the retinal degeneration in rd10 mouse.
Abstract Retinitis pigmentosa (RP) is a hereditary blinding disease characterized by neurodegeneration of photoreceptors. Retinal ganglion cells (RGCs) in animal models of RP exhibit an abnormally high spontaneous activity that interferes with signal processing. Blocking AMPA/Kainate receptors by bath application of CNQX decreases the spontaneous firing, suggesting that inhibiting these receptors in vivo may help maintain the function of inner retinal neurons in rd10 mice experiencing photoreceptor degeneration. To test this, rd10 mice were i.p. injected with CNQX or GYKI 52466 (an AMPA receptor antagonist) for 1-...
Source: Neuropharmacology - June 22, 2018 Category: Drugs & Pharmacology Authors: Xiang Z, Bao Y, Zhang J, Liu C, Xu D, Liu F, Chen H, He L, Ramakrishna S, Zhang Z, Vardi N, Xu Y Tags: Neuropharmacology Source Type: research

Prophylactic vaccination protects against the development of oxycodone self-administration.
This study was conducted to determine if immunopharmacotherapy directed against oxycodone would be capable of altering oxycodone-induced antinociception and intravenous self-administration. Male Wistar rats were administered a small-molecule immunoconjugate vaccine (Oxy-TT) or the control carrier protein, tetanus toxoid (TT), and trained to intravenously self-administer oxycodone (0.06 or 0.15 mg/kg/infusion). Brain oxycodone concentrations were 50% lower in Oxy-TT rats compared to TT rats 30 min after injection (1 mg/kg, s.c.) whereas plasma oxycodone was 15-fold higher from drug sequestration by circulating antibod...
Source: Neuropharmacology - June 21, 2018 Category: Drugs & Pharmacology Authors: Nguyen JD, Hwang CS, Grant Y, Janda KD, Taffe MA Tags: Neuropharmacology Source Type: research