Astrocytes in rapid ketamine antidepressant action.
Abstract Ketamine, a general anaesthetic and psychotomimetic drug, exerts rapid, potent and long-lasting antidepressant effect, albeit the cellular and molecular mechanisms of this action are yet to be discovered. Besides targeting neuronal NMDARs fundamental for synaptic transmission, ketamine affects the function of astroglia the key homeostatic cells of the central nervous system that contribute to pathophysiology of psychiatric diseases including depression. Here we review studies revealing that (sub)anaesthetic doses of ketamine elevate intracellular cAMP concentration ([cAMP]i) in astrocytes, attenuate stimu...
Source: Neuropharmacology - May 25, 2020 Category: Drugs & Pharmacology Authors: Stenovec M, Li B, Verkhratsky A, Zorec R Tags: Neuropharmacology Source Type: research

Glial cells as therapeutic targets for smoking cessation.
Abstract Smoking remains the leading cause of morbidity and mortality in the United States, with less than 5% of smokers attempting to quit succeeding. This low smoking cessation success rate is thought to be due to the long-term adaptations and alterations in synaptic plasticity that occur following chronic nicotine exposure and withdrawal. Glial cells have recently emerged as active players in the development of dependence phenotypes due to their roles in modulating neuronal functions and synaptic plasticity. Fundamental studies have demonstrated that microglia and astrocytes are crucial for synapse formation an...
Source: Neuropharmacology - May 24, 2020 Category: Drugs & Pharmacology Authors: Kumar M, Adeluyi A, Anderson EL, Turner JR Tags: Neuropharmacology Source Type: research

Group III metabotropic glutamate receptors regulate hypothalamic presympathetic neurons through opposing presynaptic and postsynaptic actions in hypertension.
Abstract The hypothalamic paraventricular nucleus (PVN) plays a major role in generating increased sympathetic output in hypertension. Although group III metabotropic glutamate receptors (mGluRs) are expressed in the hypothalamus, little is known about their contribution to regulating PVN presympathetic neurons in hypertension. Here we show that activating group III mGluRs with L-2-amino-4-phosphonobutyric acid (L-AP4) consistently inhibited the firing activity of spinally projecting PVN neurons in normotensive rats. However, in spontaneously hypertensive rats (SHRs), L-AP4 inhibited 45% of PVN neurons but excited...
Source: Neuropharmacology - May 23, 2020 Category: Drugs & Pharmacology Authors: Zhou JJ, Pachuau J, Li DP, Chen SR, Pan HL Tags: Neuropharmacology Source Type: research

Progression of obsessive compulsive disorder-like grooming in Sapap3 knockout mice: A longitudinal [11C]ABP688 PET study.
Abstract We aimed to evaluate [3-(6-methyl-pyridin-2-ylethynyl)-cyclohex-2-enone-0-11C-methyloxime] ([11C]ABP688) small animal positron emission tomography (μPET) as a biomarker to visualize possible longitudinal changes in metabotropic glutamate receptor 5 (mGluR5) availability in the brain of SAP90/PSD-95 associated protein 3 (Sapap3) knockout (ko) mice, showing obsessive compulsive disorder (OCD)-like behavior. METHODS: Alongside the assessment of grooming, we performed [11C]ABP688 μPET/CT imaging in wild-type (wt; n = 10) and ko (n = 11) mice both at 3 and 9 months. Using the simplified refe...
Source: Neuropharmacology - May 23, 2020 Category: Drugs & Pharmacology Authors: Glorie D, Verhaeghe J, Miranda A, Kertesz I, Wyffels L, Stroobants S, Staelens S Tags: Neuropharmacology Source Type: research

Corrigendum to "Dissociative effects of dorsomedial striatum D1 and D2 receptor antagonism in the regulation of anxiety and learned approach-avoidance conflict decision-making ˮ [Neuropharmacology 146 (2019) 222-230].
Corrigendum to "Dissociative effects of dorsomedial striatum D1 and D2 receptor antagonism in the regulation of anxiety and learned approach-avoidance conflict decision-makingˮ [Neuropharmacology 146 (2019) 222-230]. Neuropharmacology. 2020 May 23;:108154 Authors: Nguyen D, Alushaj E, Erb S, Ito R PMID: 32456783 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - May 23, 2020 Category: Drugs & Pharmacology Authors: Nguyen D, Alushaj E, Erb S, Ito R Tags: Neuropharmacology Source Type: research

Bidirectional pharmacological perturbations of the noradrenergic system differentially affect tactile detection.
In this study, we trained mice to perform a head-fixed, quantitative tactile detection task, and administered an α2 adrenergic receptor agonist or antagonist to pharmacologically down- or up-regulate LC-NE activity, respectively. We addressed the outstanding question of how bidirectional perturbations of LC-NE activity affect tactile detection, and tested whether localized and systemic drug treatments exert the same behavioral effects. We found that both localized and systemic suppression of LC-NE impaired tactile detection by reducing motivation. Surprisingly, while locally activating LC-NE enabled mice to perform i...
Source: Neuropharmacology - May 20, 2020 Category: Drugs & Pharmacology Authors: McBurney-Lin J, Sun Y, Tortorelli LS, Nguyen QA, Haga-Yamanaka S, Yang H Tags: Neuropharmacology Source Type: research

Optopharmacology reveals a differential contribution of native GABAA receptors to dendritic and somatic inhibition using azogabazine.
We report that the trans-isomer preferentially binds and inhibits GABAAR function, whilst promotion of the cis-isomer caused unbinding of azogabazine from GABAARs. Using cultured cerebellar granule cells, azogabazine in conjunction with UV light applied to defined membrane domains, revealed higher densities of GABAARs at somatic inhibitory synapses compared to those populating proximal dendritic zones, even though the latter displayed a higher number of synapses per unit area of membrane. Azogabazine also revealed more pronounced GABA-mediated inhibition of action potential firing in proximal dendrites compared to the soma...
Source: Neuropharmacology - May 20, 2020 Category: Drugs & Pharmacology Authors: Mortensen M, Huckvale R, Pandurangan AP, Baker JR, Smart TG Tags: Neuropharmacology Source Type: research

Ghrelin acts in the brain to block colonic hyperpermeability in response to lipopolysaccharide through the vagus nerve.
Abstract Brain ghrelin plays a role in gastrointestinal functions. Among them, ghrelin acts centrally to stimulate gastrointestinal motility and induce visceral antinociception. Intestinal barrier function, one of important gastrointestinal functions, is also controlled by the central nervous system. Little is, however, known about a role of central ghrelin in regulation of intestinal permeability. The present study was performed to clarify whether brain ghrelin is also involved in regulation of intestinal barrier function and its mechanism. Colonic permeability was estimated in vivo by quantifying the absorbed Ev...
Source: Neuropharmacology - May 19, 2020 Category: Drugs & Pharmacology Authors: Ishioh M, Nozu T, Igarashi S, Tanabe H, Kumei S, Ohhira M, Okumura T Tags: Neuropharmacology Source Type: research

Acetylcholinesterase inhibition resulting from exposure to inhaled OP can be prevented by pretreatment with BChE in both macaques and minipigs.
Abstract More frequent and widespread nerve agent attacks highlight the need for efficacious pre- and post-exposure organophosphate (OP) counter-measures to protect military and civilian populations. Because of critical targeting of acetylcholinesterase (AChE) in the CNS by OPs, a pre-treatment candidate for preventing/reducing poisoning will be broadly acting molecules that scavenges OPs in blood before they reach their physiological targets. Prophylactic human butyrylcholinesterase (HuBChE), the leading pretreatment candidate, has been shown to protect against multiple LD50's of nerve agents in rodents, macaques...
Source: Neuropharmacology - May 19, 2020 Category: Drugs & Pharmacology Authors: Rosenberg Y, Saxena A Tags: Neuropharmacology Source Type: research

Endogenous opioid peptides in the descending pain modulatory circuit.
Abstract The opioid epidemic has led to a serious examination of the use of opioids for the treatment of pain. Opioid drugs are effective due to the expression of opioid receptors throughout the body. These receptors respond to endogenous opioid peptides that are expressed as polypeptide hormones that are processed by proteolytic cleavage. Endogenous opioids are expressed throughout the peripheral and central nervous system and regulate many different neuronal circuits and functions. One of the key functions of endogenous opioid peptides are to modulate our responses to pain. This review will focus on the descendi...
Source: Neuropharmacology - May 15, 2020 Category: Drugs & Pharmacology Authors: Bagley EE, Ingram SL Tags: Neuropharmacology Source Type: research

The effects of acetylcholinesterase inhibitors on morbidity after general anesthesia and surgery.
Abstract Non-depolarizing neuromuscular blocking agents are used during general anesthesia to facilitate intubation and optimize surgical conditions. When patients leave the operating room after surgery, postoperative residual neuromuscular block occurs frequently, increasing vulnerability to respiratory complications such as hypoxemia and unplanned postoperative mechanical ventilation. To restore neuromuscular transmission and skeletal muscle strength, anesthesiologists typically administer peripherally acting acetylcholinesterase inhibitors such as neostigmine. However, neostigmine's desirable effects have a nar...
Source: Neuropharmacology - May 13, 2020 Category: Drugs & Pharmacology Authors: Shaydenfish D, Wongtangman K, Eikermann M, Schaefer MS Tags: Neuropharmacology Source Type: research

A regulatory pathway linking caffeine action, mood and the diurnal clock.
This study provides a link between caffeine, diurnal signaling and mood-related behaviors, which may open new perspectives for our understanding of antidepressant mechanisms in the mouse brain. PMID: 32413367 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - May 12, 2020 Category: Drugs & Pharmacology Authors: Trautmann C, Burek D, Hübner CA, Girault JA, Engmann O Tags: Neuropharmacology Source Type: research

Impact of nicotine, alcohol, and cocaine exposure on germline integrity and epigenome.
Abstract Converging evidence suggests that parental exposure to drugs of abuse can affect offspring phenotypes. The impacts of drug abuse on germ cell quality may mediate multigenerational and transgenerational inheritance, although biological pathways underlying this mode of inheritance are not yet characterized. Germline epigenetic marks are modified by drug exposure and have emerged as promising mechanistic candidates in recent work. Drug exposure also impacts overall germline integrity and reproductive functioning, although the role of these consequences in multi/transgenerational inheritance is unclear. This ...
Source: Neuropharmacology - May 12, 2020 Category: Drugs & Pharmacology Authors: Zeid D, Gould TJ Tags: Neuropharmacology Source Type: research

Future avenues for Alzheimer's disease detection and therapy: Liquid biopsy, intracellular signaling modulation, systems pharmacology drug discovery.
itiative (APMI) Abstract Once first Alzheimer's disease (AD) disease-modifying therapies will become available, global healthcare systems will be challenged by a large-scale demand for clinical and biological screening. Validation and qualification of globally accessible, minimally-invasive, and time-, cost-saving blood-based biomarkers needs to be advanced. Besides established pathophysiological pathways, novel mechanisms (and related candidate biomarkers) - including distinct neuroinflammation pathways (TREM2 and YKL-40), axonal degeneration (neurofilament light chain protein), synaptic dysfunction (neurogranin,...
Source: Neuropharmacology - May 11, 2020 Category: Drugs & Pharmacology Authors: Hampel H, Vergallo A, Caraci F, Cuello AC, Lemercier P, Vellas B, Giudici KV, Baldacci F, Hänisch B, Haberkamp M, Broich K, Nisticò R, Emanuele E, Llavero F, Zugaza JL, Lucía A, Giacobini E, Lista S, Alzheimer Precision Medicine Initiative (APMI) Tags: Neuropharmacology Source Type: research

Antidepressive properties of macrophage-colony stimulating factor in a mouse model of depression induced by chronic unpredictable stress.
Abstract Previous studies have reported that macrophage-colony stimulating factor (M-CSF), a drug that is used to treat hematological system disease, can ameliorate chronic stress-induced depressive-like behaviors in mice. This indicates that M-CSF could be developed into a novel antidepressant. Here, we investigated the antidepressive properties of M-CSF, aiming to explore its potential values in depression treatment. Our results showed that a single M-CSF injection at the dose of 75 and 100 μg/kg, but not at 25 or 50 μg/kg, ameliorated chronic unpredictable stress (CUS)-induced depressive-like behavior...
Source: Neuropharmacology - May 11, 2020 Category: Drugs & Pharmacology Authors: Ye T, Wang D, Cai Z, Tong L, Chen Z, Lu J, Lu X, Huang C, Yuan X Tags: Neuropharmacology Source Type: research

Negative allosteric modulation of GluN1/GluN3 NMDA receptors.
Abstract NMDA receptors are ligand-gated ion channels that mediate excitatory neurotransmission. Most native NMDA receptors are tetrameric assemblies of two glycine-binding GluN1 and two glutamate-binding GluN2 subunits. Co-assembly of the glycine-binding GluN1 with glycine-binding GluN3 subunits (GluN3A-B) creates glycine-activated receptors that possess strikingly different functional and pharmacological properties compared to GluN1/GluN2 NMDA receptors. The role of GluN1/GluN3 receptors in neuronal function remains unknown, in part due to lack of pharmacological tools with which to explore their physiological r...
Source: Neuropharmacology - May 7, 2020 Category: Drugs & Pharmacology Authors: Zhu Z, Yi F, Epplin MP, Liu D, Summer SL, Mizu R, Shaulsky G, XiangWei W, Tang W, Burger PB, Menaldino DS, Myers SJ, Liotta DC, Hansen KB, Yuan H, Traynelis SF Tags: Neuropharmacology Source Type: research

Modulation of expression of fear by oxytocin signaling in the central amygdala: From reduction of fear to regulation of defensive behavior style.
Abstract Many studies in preclinical animal models have described fear-reducing effects of the neuropeptide oxytocin in the central nucleus of the amygdala. However, recent studies have refined the role of oxytocin in the central amygdala, which may extend to the selection of an active defensive coping style in the face of immediate threat, and also fear-enhancing effects have been reported. On top of this, oxytocin enables the discrimination of unfamiliar conspecifics on the basis of their emotional state, which could allow for the selection of an appropriate coping style. This is in line with many observations t...
Source: Neuropharmacology - May 7, 2020 Category: Drugs & Pharmacology Authors: van den Burg EH, Hegoburu C Tags: Neuropharmacology Source Type: research

Cebranopadol reduces cocaine self-administration in male rats: Dose, treatment and safety consideration.
Abstract As a novel first-in-class potent analgesic acting as an agonist of multiple opioid receptors, cebranopadol showed high efficacy and good tolerability in a broad range of preclinical models and clinical trials related to pain. In the present study, to evaluate the efficacy and safety of cebranopadol as a potential treatment of cocaine dependence, we tested the effects of cebranopadol with single and repeated doses (25, 50, 75, or 100 μg/kg, oral gavage) using rat models of cocaine fixed-ratio (FR) self-administration (SA), cocaine progressive-ratio (PR) SA, and sucrose pellet SA. In single-dosing trea...
Source: Neuropharmacology - May 7, 2020 Category: Drugs & Pharmacology Authors: Wei H, Zhang T, Zhan CG, Zheng F Tags: Neuropharmacology Source Type: research

Opportunities for multiscale computational modelling of serotonergic drug effects in Alzheimer's disease.
Abstract Alzheimer's disease (AD) is an age-specific neurodegenerative disease that compromises cognitive functioning and impacts the quality of life of an individual. Pathologically, AD is characterised by abnormal accumulation of beta-amyloid (Aβ) and hyperphosphorylated tau protein. Despite research advances over the last few decades, there is currently still no cure for AD. Although, medications are available to control some behavioural symptoms and slow the disease's progression, most prescribed medications are based on cholinesterase inhibitors. Over the last decade, there has been increased attention t...
Source: Neuropharmacology - May 4, 2020 Category: Drugs & Pharmacology Authors: Joshi A, Wang DH, Watterson S, McClean PL, Behera CK, Sharp T, Wong-Lin K Tags: Neuropharmacology Source Type: research

Ventral tegmental area GABAergic neurons induce anxiety-like behaviors and promote palatable food intake.
Abstract The obesity epidemic is a global problem and a great challenge for public health. Overconsumption of food, especially palatable food, is the leading cause of obesity. The precise neural circuits underlying food overconsumption remain unclear and require further characterization. In the present study, we showed that Ca2+ signals of GABAergic neurons within the ventral tegmental area (VTA) increased after the onset of food intake, especially high-fat or high-sugar chow. Optogenetic activation of VTA GABAergic neurons evoked immediate eating of palatable food and significantly increased palatable food intake...
Source: Neuropharmacology - May 3, 2020 Category: Drugs & Pharmacology Authors: Chen L, Lu YP, Chen HY, Huang SN, Guo YR, Zhang JY, Li QX, Luo CY, Lin SW, Chen ZN, Hu LH, Wang WX, Li HY, Cai P, Yu CX Tags: Neuropharmacology Source Type: research

Repeated norepinephrine receptor stimulation in the BNST induces sensorimotor gating deficits via corticotropin releasing factor.
Abstract Intense stress precipitates symptoms in disorders such as post-traumatic stress (PTSD) and schizophrenia. Patients with these disorders have dysfunctional sensorimotor gating as indexed by disrupted prepulse inhibition of the startle response (PPI), which refers to decreased startle response when a weak pre-stimulus precedes a startling stimulus. Stress promotes release of norepinephrine (NE) and corticotrophin releasing factor (CRF) within the brain, neurotransmitters that also modulate PPI. We have shown that repeated stress causes sensitization of NE receptors within the basolateral amygdala (BLA) via ...
Source: Neuropharmacology - April 29, 2020 Category: Drugs & Pharmacology Authors: Rajbhandari AK, Bakshi VP Tags: Neuropharmacology Source Type: research

Tau immunotherapies: Lessons learned, current status and future considerations.
Abstract The majority of clinical trials targeting the tau protein in Alzheimer's disease and other tauopathies are tau immunotherapies. Because tau pathology correlates better with the degree of dementia than amyloid-β lesions, targeting tau is likely to be more effective in improving cognition than clearing amyloid-β in Alzheimer's disease. However, the development of tau therapies is in many ways more complex than for amyloid-β therapies as briefly outlined in this review. Most of the trials are on humanized antibodies, which may have very different properties than the original mouse antibodies. ...
Source: Neuropharmacology - April 28, 2020 Category: Drugs & Pharmacology Authors: Sandusky-Beltran LA, Sigurdsson EM Tags: Neuropharmacology Source Type: research

Lessons from nature: Structural studies and drug design driven by a homologous surrogate from invertebrates, AChBP.
Abstract It has been almost 20 years since the discovery and crystallization of a structural surrogate, the Lymnaea stagnalis acetylcholine binding protein (Ls-AChBP), comprising the extracellular domain of the nicotinic acetylcholine receptors (nAChRs). Structural characterization of this soluble protein has increased our understanding of the requirements for agonist and antagonist interactions at the ligand recognition site of the nAChRs. Application can be extended to orthologs in the pentameric ligand-gated ion channel superfamily, encompassing receptors that depolarize or hyperpolarize upon neurotransmitter a...
Source: Neuropharmacology - April 27, 2020 Category: Drugs & Pharmacology Authors: Camacho-Hernandez GA, Taylor P Tags: Neuropharmacology Source Type: research

In vitro and in vivo pharmacological characterization of the synthetic opioid MT-45.
Abstract MT-45 is a synthetic opioid that was developed in the 1970s as an analgesic compound. However, in recent years MT-45 has been associated with multiple deaths in Europe and has been included in the class of novel psychoactive substances known as novel synthetic opioids (NSOs). Little is known about the pharmaco-toxicological effects of MT-45. Therefore, we used a dynamic mass redistribution (DMR) assay to investigate the pharmacodynamic profile of this NSO in vitro compared with morphine. We then used in vivo studies to investigate the effect of the acute systemic administration of MT-45 (0.01-15 mg/kg i...
Source: Neuropharmacology - April 25, 2020 Category: Drugs & Pharmacology Authors: S B, Neto J A, R A, M T, A G, G S, De-Giorgio F, P F, M N, G C, M M Tags: Neuropharmacology Source Type: research

Insulin and leptin as potential cognitive enhancers in metabolic disorders and Alzheimer's disease.
Abstract Recent clinical and epidemiological observations point to a correlation between disorders of energy metabolism, such as obesity and diabetes, and cognitive decline and dementia. Many studies indicate that these age-related conditions closely interact with each other, but the underlying molecular and physiological mechanisms for such correlations are largely unknown. Insulin and leptin, hormones classically implicated in diabetes and obesity, are gaining increasing attention for their participation in cognitive processes and memory. Disrupted signaling by those hormones is associated with impaired brain fu...
Source: Neuropharmacology - April 25, 2020 Category: Drugs & Pharmacology Authors: Mejido DCP, Andrade J, Vieira MNN, Ferreira ST, De Felice FG Tags: Neuropharmacology Source Type: research

Acute vitamin B12 supplementation evokes antidepressant response and alters Ntrk-2.
n O Abstract Depression is the leading cause of disability worldwide. Although most research into risk factors focuses on stress, dietary factors also have a strong link with depression. For instance, chronic vitamin B12-supplementation may reduce depression risk and helps to reverse the prodepressive effects of early life stress in animal models. However, it is still unclear whether a single acute dose of vitamin B12 is sufficient to induce antidepressant effects on molecular or behavioral levels. Based on pharmacological work and CRISPR-dCas9 epigenome editing in Neuro2A-cells we provide in vitro evidence for a ...
Source: Neuropharmacology - April 23, 2020 Category: Drugs & Pharmacology Authors: Trautmann C, Bock A, Urbach A, Hübner C, Engmann O Tags: Neuropharmacology Source Type: research

Double dissociation between actions of dopamine D1 and D2 receptors of the ventral and dorsolateral striatum to produce reinstatement of cocaine seeking behavior.
Abstract One of the hallmarks of addiction is the enduring vulnerability to relapse. Following repeated use, cocaine (COC) induces neuroadaptations within the dopamine (DA) system, arguably underlying several aspects of COC-seeking behavior. Peripheral stimulation of D2, but not D1, receptors induces relapse. However, where in the brain these effects occur is still matter of debate. The D1 and D2 receptors (D1R; D2R) are highly expressed in the nucleus accumbens (NAcc) and the dorsolateral striatum (DLS), but their specific involvement in the reinstatement of COC-seeking remains elusive. We assessed the reinstatin...
Source: Neuropharmacology - April 23, 2020 Category: Drugs & Pharmacology Authors: Campos RC, Dias C, Darlot F, Cador M Tags: Neuropharmacology Source Type: research

Efficient detoxification of nerve agents by oxime-assisted reactivation of acetylcholinesterase mutants.
Abstract The recent advancements in crystallography and kinetics studies involving reactivation mechanism of acetylcholinesterase (AChE) inhibited by nerve agents have enabled a new paradigm in the search for potent medical countermeasures in case of nerve agents exposure. Poisonings by organophosphorus compounds (OP) that lead to life-threatening toxic manifestations require immediate treatment that combines administration of anticholinergic drugs and an aldoxime as a reactivator of AChE. An alternative approach to reduce the in vivo toxicity of OP centers on the use of bioscavengers against the parent organophos...
Source: Neuropharmacology - April 22, 2020 Category: Drugs & Pharmacology Authors: Kovarik Z, Hrvat NM Tags: Neuropharmacology Source Type: research

MK-801 impairs working memory on the Trial-Unique Nonmatch-to-Location test in mice, but this is not exclusively mediated by NMDA receptors on PV+ interneurons or forebrain pyramidal cells.
Abstract NMDA receptors are widely expressed throughout the brain on many cell types, and loss of function of these receptors (ie: NMDAr hypofunction) is a candidate mechanism explaining working memory impairment in schizophrenia. However, the cellular source driving the working memory deficits caused by NMDA hypofunction has not been explored. The aim of this study was to assess the contribution of NMDAr on pyramidal cells and parvalbumin (PV+) interneurons to impairments in working memory induced by NMDAr hypofunction. We excised GluN1 - the gene encoding the obligatory subunit of the NMDAr from PV + i...
Source: Neuropharmacology - April 21, 2020 Category: Drugs & Pharmacology Authors: Sokolenko E, Nithianantharajah J, Jones NC Tags: Neuropharmacology Source Type: research

The role of pituitary adenylyl cyclase-activating polypeptide in the motivational effects of addictive drugs.
Abstract Pituitary adenylyl cyclase activating polypeptide (PACAP) was originally isolated from the hypothalamus and found to stimulate adenylyl cyclase in the pituitary. Later studies showed that this peptide and its receptors (PAC1, VPAC1, and VPAC2) are widely expressed in the central nervous system (CNS). Consistent with its distribution in the CNS, the PACAP/PAC1 receptor system is involved in several physiological responses, such as mediation of the stress response, modulation of nociception, regulation of prolactin release, food intake, etc. This system is also implicated in different pathological states, e...
Source: Neuropharmacology - April 20, 2020 Category: Drugs & Pharmacology Authors: Stojakovic A, Ahmad SM, Malhotra S, Afzal Z, Ahmed M, Lutfy K Tags: Neuropharmacology Source Type: research

Hippocampal synaptic dysfunction in the SOD1G93A mouse model of Amyotrophic Lateral Sclerosis: Reversal by adenosine A2AR blockade.
M, Vaz SH Abstract Amyotrophic Lateral Sclerosis (ALS) mostly affects motor neurons, but non-motor neural and cognitive alterations have been reported in ALS mouse models and patients. Here, we evaluated if time-dependent biphasic changes in synaptic transmission and plasticity occur in hippocampal synapses of ALS SOD1G93A mice. Recordings were performed in hippocampal slices of SOD1G93A and age-matched WT mice, in the pre-symptomatic and symptomatic stages. We found an enhancement of pre-synaptic function and increased adenosine A2A receptor levels in the hippocampus of pre-symptomatic mice. In contrast, in sympt...
Source: Neuropharmacology - April 17, 2020 Category: Drugs & Pharmacology Authors: N R, Rombo DM, Ferreira MF, Baqi Y, Müller CE, Ribeiro JA, Sebastião AM, Vaz SH Tags: Neuropharmacology Source Type: research

Rewarding information presented during reactivation attenuates fear memory: Methylphenidate and fear memory updating.
res L Abstract In the last decade it became clear that a previously consolidated memory can be modified during the plastic state induced by retrieval. This updating process opens the possibility to adapt undesired memory. Here we investigated whether fear memory could be updated to less-aversive/positive level by inserting hedonic information during retrieval. Considering that methylphenidate has strong rewarding propriety, we injected 3 or 10 mg/kg pre or post-reactivation in rats previously trained in contextual fear conditioning. We found that memory reactivation under effect of methylphenidate attenuates fea...
Source: Neuropharmacology - April 16, 2020 Category: Drugs & Pharmacology Authors: Arellano Pérez AD, Popik B, de Oliveira Alvares L Tags: Neuropharmacology Source Type: research

Oxytocin treatment for alcoholism: Potential neurocircuitry targets.
Abstract Oxytocin (OT) has gained considerable interest in recent years as a potential treatment for alcoholism and other substance use disorders. Evidence continues to mount that OT administered either centrally, peripherally or intranasally can decrease ethanol intake in both humans and animal models. The potential mechanisms for the ability of OT to decrease ethanol reward, and importantly, cue- and stress-induced ethanol relapse, are explored by reviewing the specific neuronal circuits involved in mediating these actions and their sensitivity to OT. In addition to dopamine neurons that project from ventral teg...
Source: Neuropharmacology - April 15, 2020 Category: Drugs & Pharmacology Authors: Peris J, Steck M, Krause EG Tags: Neuropharmacology Source Type: research

Possible synergies between isatin, an endogenous MAO inhibitor, and antiparkinsonian agents on the dopamine release from striatum of freely moving rats.
e;n R Abstract Isatin is an endogenous indole that inhibits monoamine oxidase (MAO). When exogenously administered, it increases the striatal dopamine and acetylcholine levels and presents neuroprotective effects in the brain. Previous studies show that intrastriatal administration of isatin increased the in vivo dopamine release from striatum in a concentration-dependent form. In the present work, we investigated the effects of combined administration of isatin together with other substances actually used in antiparkinsonian pharmacotherapy on in vivo dopamine overflow. For this, we co-administered isatin with th...
Source: Neuropharmacology - April 15, 2020 Category: Drugs & Pharmacology Authors: Faro LRF, Justo LA, Alfonso M, Durán R Tags: Neuropharmacology Source Type: research

Maturation of newborn neurons predicts social memory persistence in mice.
Abstract Memory transience is essential to gain cognitive flexibility. Recently, hippocampal neurogenesis is emerging as one of the mechanisms involved in the balance between persistence and forgetting. Social recognition memory (SRM) has its duration prolonged by neurogenesis. However, it is still to be determined whether boosting neurogenesis in distinct phases of SRM may favor forgetting over persistence. In the present study, we used enriched environment (EE) and memantine (MEM) to increase neurogenesis. SRM was ubiquitously prolonged by both, while EE after the memory acquisition did not favor forgetting. Int...
Source: Neuropharmacology - April 14, 2020 Category: Drugs & Pharmacology Authors: Jaimes LF, Mansk LMZ, Almeida-Santos AF, Pereira GS Tags: Neuropharmacology Source Type: research

Inhibition of EZH2 attenuates inhibitory synaptic transmission via the pro-inflammatory pathway in rats.
This study focused on exploring whether EZH2 regulated gamma-aminobutyric acid (GABA)-mediated neurotransmission during seizure generation. Hyperthermia-induced seizures were generated in Sprague-Dawley (SD) rats using a hot (43.5 °C) bath method, and seizure severity was evaluated according to the Racine scale. The effect of treatment with the EZH2 pharmacological inhibitor GSK 126 on the GABA and pro-inflammatory cytokine levels was tested using enzyme-linked immunosorbent assay (ELISA). Miniature inhibitory postsynaptic currents (mIPSCs) were recorded using whole-cell patch clamp. In this study, our results showed...
Source: Neuropharmacology - April 13, 2020 Category: Drugs & Pharmacology Authors: Zhang Y, Han Y, Chen Z, Zhao D, Xia Q Tags: Neuropharmacology Source Type: research

Modulation of cholinergic activity through lynx prototoxins: Implications for cognition and anxiety regulation.
PMID: 32298703 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - April 13, 2020 Category: Drugs & Pharmacology Authors: Miwa JM, Anderson KR, Rogu PJ Tags: Neuropharmacology Source Type: research

Pain-modulating effects of oxytocin in patients with chronic low back pain.
Abstract The neuropeptide oxytocin (OT) has been shown to play a modulatory role in nociception. However, analgesic effects of OT in chronic pain conditions remain elusive and the neural underpinnings have not yet been investigated in humans. Here, we conducted an exploratory, randomized, placebo-controlled, cross-over study to examine effects of intranasal OT in male patients suffering from chronic low back pain (CBP) versus healthy controls (HC). N = 22 participants with CBP and 22 HCs were scanned using functional magnetic resonance imaging (fMRI) while they continuously rated either spontaneously occurri...
Source: Neuropharmacology - April 13, 2020 Category: Drugs & Pharmacology Authors: Boll S, Ueltzhoeffer K, Roth C, Bertsch K, Desch S, Nees F, Grinevich V, Herpertz SC Tags: Neuropharmacology Source Type: research

New hopes for disease modification in Parkinson's Disease.
Abstract To date, despite numerous clinical trials, no intervention has been demonstrated to modify the progression of Parkinson's disease (PD). However, over the past decades encouraging progress has been made towards a better understanding of molecular pathways relevant for the neurodegenerative process in PD. This is also based on new insights into the genetic architecture of the disease, revealing multiple novel targets for potentially disease-modifying interventions. Important achievements have also been made in the field of risk markers, and combinations thereof, in the form of risk algorithms, will hopefull...
Source: Neuropharmacology - April 13, 2020 Category: Drugs & Pharmacology Authors: Poewe W, Seppi K, Marini K, Mahlknecht P Tags: Neuropharmacology Source Type: research

Lactate enhances Arc/arg3.1 expression through hydroxycarboxylic acid receptor 1- β-arrestin2 pathway in astrocytes.
Lactate enhances Arc/arg3.1 expression through hydroxycarboxylic acid receptor 1-β-arrestin2 pathway in astrocytes. Neuropharmacology. 2020 Apr 12;:108084 Authors: Ma K, Ding X, Song Q, Han Z, Yao H, Ding J, Hu G Abstract In recent years, with the discovery and research of lactate-specific receptor HCAR1(hydroxycarboxylic acid receptor 1), lactate is not only as a product of Glycolysis in astrocytes, but also as a signaling molecule which has gradually received attention. Studies have found that lactate can be used as an intercellular signaling molecule involved in synaptic plasticity, and so tha...
Source: Neuropharmacology - April 12, 2020 Category: Drugs & Pharmacology Authors: Ma K, Ding X, Song Q, Han Z, Yao H, Ding J, Hu G Tags: Neuropharmacology Source Type: research

NADPH oxidase contributes to oxidative damage and mitochondrial impairment induced by acute ethanol treatment in rat hippocampal neurons.
la RA Abstract Acute ethanol treatment induces neurodegeneration in cultured neurons and can lead to brain damage in animal models. Neuronal cells exposed to ethanol showed an increase in reactive oxygen species (ROS), oxidative damage and mitochondrial impairment contributing to synaptic failure. However, the underlying mechanisms of these events are not well understood. Here, we studied the contribution of NADPH oxidase, as a relevant source of ROS production in the brain, to mitochondrial impairment and oxidative stress induced by ethanol. We used primary hippocampal neurons subjected to an acute treatment of e...
Source: Neuropharmacology - April 11, 2020 Category: Drugs & Pharmacology Authors: Pérez MJ, Loyola R, Canelo F, Aranguiz A, Tapia-Monsalves C, Osorio-Fuentealba C, Quintanilla RA Tags: Neuropharmacology Source Type: research

Inhibiting the interaction between apoptosis inducing factor and cyclophilin a prevents brain injury in neonatal mice after hypoxia-ischemia.
Abstract The interaction between apoptosis-inducing factor (AIF) and cyclophilin A (CypA) has been shown to contribute to caspase-independent apoptosis. Blocking the AIF/CypA interaction protects against glutamate-induced neuronal cell death in vitro, and the purpose of this study was to determine the in vivo effect of an AIF/CypA interaction blocking peptide (AIF(370-394)-TAT) on neonatal mouse brain injury after hypoxia ischemia (HI). The pups were treated with AIF (370-394)-TAT peptide intranasally prior to HI. Brain injury was significantly reduced at 72 h after HI in the AIF(370-394)-TAT peptide treatment g...
Source: Neuropharmacology - April 8, 2020 Category: Drugs & Pharmacology Authors: Rodriguez J, Xie C, Li T, Sun Y, Wang Y, Xu Y, Li K, Zhang S, Zhou K, Wang Y, Mallard C, Hagberg H, Doti N, Wang X, Zhu C Tags: Neuropharmacology Source Type: research

Progress in nicotinic receptor structural biology.
Abstract Here we begin by briefly reviewing landmark structural studies on the nicotinic acetylcholine receptor. We highlight challenges that had to be overcome to push through resolution barriers, then focus on what has been gleaned in the past few years from crystallographic and single particle cryo-EM studies of different nicotinic receptor subunit assemblies and ligand complexes. We discuss insights into ligand recognition, ion permeation, and allosteric gating. We then highlight some foundational aspects of nicotinic receptor structural biology that remain unresolved and are areas ripe for future exploration....
Source: Neuropharmacology - April 7, 2020 Category: Drugs & Pharmacology Authors: Gharpure A, Noviello CM, Hibbs RE Tags: Neuropharmacology Source Type: research

Neurotensin induces hypothermia by activating both neuronal neurotensin receptor 1 and astrocytic neurotensin receptor 2 in the median preoptic nucleus.
Abstract Neurotensin (NTS) is a neuropeptide acting as a neuromodulator in the brain and is a very potent hypothermic agent. However, the cellular mechanisms of actions are not fully understood. Here we report that NTS increases the firing rate of preoptic GABAergic neurons by activating both neurotensin receptor 1 (NTSR1) and neurotensin receptor 2 (NTSR2), expressed by neurons and astrocytes, respectively. Downstream of NTSR1 the neuropeptide activated an inward current, calcium release from intracellular stores and, postsynaptically, increased frequency and amplitude of inhibitory synaptic events. NTSR2 activat...
Source: Neuropharmacology - April 7, 2020 Category: Drugs & Pharmacology Authors: Tabarean I Tags: Neuropharmacology Source Type: research

Neuropathic and cAMP-induced pain behavior is ameliorated in mice lacking CNGB1.
ko A Abstract Cyclic nucleotide-gated (CNG) channels, which are directly activated by cAMP and cGMP, have long been known to play a key role in retinal and olfactory signal transduction. Emerging evidence indicates that CNG channels are also involved in signaling pathways important for pain processing. Here, we found that the expression of the channel subunits CNGA2, CNGA3, CNGA4 and CNGB1 in dorsal root ganglia, and of CNGA2 in the spinal cord, is transiently altered after peripheral nerve injury in mice. Specifically, we show using in situ hybridization and quantitative real-time RT-PCR that CNG channels contain...
Source: Neuropharmacology - April 6, 2020 Category: Drugs & Pharmacology Authors: Kallenborn-Gerhardt W, Metzner K, Lu R, Petersen J, Kuth MS, Heine S, Drees O, Paul M, Becirovic E, Kennel L, Flauaus C, Groß T, Wack G, Hohmann SW, Nemirovski D, Del Turco D, Biel M, Geisslinger G, Michalakis S, Schmidtko A Tags: Neuropharmacology Source Type: research

Examining the role of muscarinic M5 receptors in VTA cholinergic modulation of depressive-like and anxiety-related behaviors in rats.
Abstract Acetylcholine is implicated in mood disorders including depression and anxiety. Increased cholinergic tone in humans and rodents produces pro-depressive and anxiogenic-like effects. Cholinergic receptors in the ventral tegmental area (VTA) are known to mediate these responses in male rats, as measured by the sucrose preference test (SPT), elevated plus maze (EPM), and the forced swim test (FST). However, these effects have not been examined in females, and the VTA muscarinic receptor subtype(s) mediating the pro-depressive and anxiogenic-like behavioral effects of increased cholinergic tone are unknown. W...
Source: Neuropharmacology - April 5, 2020 Category: Drugs & Pharmacology Authors: Nunes EJ, Rupprecht LE, Foster DJ, Lindsley CW, Conn PJ, Addy NA Tags: Neuropharmacology Source Type: research

Oxytocin in the neural control of eating: At the crossroad between homeostatic and non-homeostatic signals.
Abstract The understanding of the biological substrates regulating feeding behavior is relevant to address the health problems related to food overconsumption. Several studies have expanded the conventional view of the homeostatic regulation of body weight mainly orchestrated by the hypothalamus, to include also the non-homeostatic control of appetite. Such processes include food reward and are mainly coordinated by the activation of the central mesolimbic dopaminergic pathway. The identification of endogenous systems acting as a bridge between homoeostatic and non-homeostatic pathways might represent a significan...
Source: Neuropharmacology - April 4, 2020 Category: Drugs & Pharmacology Authors: Romano A, Friuli M, Cifani C, Gaetani S Tags: Neuropharmacology Source Type: research

Acetylcholinesterase inhibitor exposures as an initiating factor in the development of Gulf War Illness, a chronic neuroimmune disorder in deployed veterans.
Abstract Gulf War Illness (GWI) is a chronic multi-symptom disorder, characterized by symptoms such as fatigue, pain, cognitive and memory impairment, respiratory, skin and gastrointestinal problems, that is experienced by approximately one-third of 1991 Gulf War veterans. Over the nearly three decades since the end of the war, investigators have worked to elucidate the initiating factors and underlying causes of GWI. A significant portion of this research has indicated a strong correlation between GWI and exposure to a number of different acetycholinesterase inhibitors (AChEIs) in theater, such as sarin and cyclo...
Source: Neuropharmacology - April 2, 2020 Category: Drugs & Pharmacology Authors: Michalovicz LT, Kelly KA, Sullivan K, O'Callaghan JP Tags: Neuropharmacology Source Type: research

Differential effects of traxoprodil and S-ketamine on quantitative EEG and auditory event-related potentials as translational biomarkers in preclinical trials in rats and mice.
In conclusion, ketamine and traxoprodil showed very different effects on diverse EEG readouts differentiating selective GluN2B antagonism from non-selective pan-NMDA-R antagonists like ketamine. These readouts are thus perfectly suited to support drug discovery efforts on NMDA-R and understanding the different functions of NMDA-R subtypes. PMID: 32243874 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - March 31, 2020 Category: Drugs & Pharmacology Authors: Raith H, Schuelert N, Duveau V, Roucard C, Plano A, Dorner-Ciossek C, Ferger B Tags: Neuropharmacology Source Type: research

Multi-modal imaging reveals differential brain volumetric, biochemical, and white matter fiber responsivity to repeated intermittent ethanol vapor exposure in male and female rats.
Abstract A generally accepted framework derived predominately from animal models asserts that repeated cycles of chronic intermittent ethanol (EtOH; CIE) exposure cause progressive brain adaptations associated with anxiety and stress that promote voluntary drinking, alcohol dependence, and further brain changes that contribute to the pathogenesis of alcoholism. The current study used CIE exposure via vapor chambers to test the hypothesis that repeated episodes of withdrawals from chronic EtOH would be associated with accrual of brain damage as quantified using in vivo magnetic resonance imaging (MRI), diffusion te...
Source: Neuropharmacology - March 30, 2020 Category: Drugs & Pharmacology Authors: Zahr NM, Lenart AM, Karpf JA, Casey KM, Pohl KM, Sullivan EV, Pfefferbaum A Tags: Neuropharmacology Source Type: research