Peripubertal cannabidiol treatment rescued behavioral and neurochemical abnormalities in MAM model of schizophrenia.
Abstract In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produced long-lasting behavioral alterations such as social withdrawal and cognitive impairment in the social interaction test and in the novel object recognition test, respectively. At molecular level, an increased cannabinoid receptor type-1 (CB1) mRNA and protein expression which might be due to a reduction in DNA methylation at gene promoter in the prefrontal cortex (PFC), coincided with deficits in the social interaction test ...
Source: Neuropharmacology - November 26, 2018 Category: Drugs & Pharmacology Authors: Stark T, Ruda-Kucerova J, Iannotti FA, D'Addario C, Di Marco R, Pekarik V, Drazanova E, Piscitelli F, Bari M, Babinska Z, Giurdanella G, Di Bartolomeo M, Salomone S, Sulcova A, Maccarrone M, Wotjak CT, Starcuk Z, Drago F, Mechoulam R, Di Marzo V, Micale V Tags: Neuropharmacology Source Type: research
Early life stress alters the developmental trajectory of corticolimbic endocannabinoid signaling in male rats.
Abstract Early-life stress modulates the development of cortico-limbic circuits and increases vulnerability to adult psychopathology. Given the important stress-buffering role of endocannabinoid (eCB) signaling, we performed a comprehensive investigation of the developmental trajectory of the eCB system and the impact of exposure to early life stress induced by repeated maternal separation (MS; 3 h/day) from postnatal day 2 (PND2) to PND12. Tissue levels of the eCB molecules anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were measured after MS exposures, as well under basal conditions at juvenile (PND14), ad...
Source: Neuropharmacology - November 26, 2018 Category: Drugs & Pharmacology Authors: Hill MN, Eiland L, Lee TTY, Hillard CJ, McEwen BS Tags: Neuropharmacology Source Type: research
Ketamine may exert antidepressant effects via suppressing NLRP3 inflammasome to upregulate AMPA receptors.
Abstract Recent studies have indicated that sub-anesthetic dose of ketamine exerts rapid antidepressant effects. Upregulation of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors contributes to rapid antidepressant effects of ketamine. A recent study indicated that the increasing expression of AMPARs is related to the inhibition of NLRP3 inflammasome. Thus, we postulated that NLRP3 inflammasome might play an important role in ketamine's antidepressant effects. We found that sub-anesthesia dose of ketamine (10ml/kg) ameliorated LPS-induced depressive-like behaviors, including decreased suc...
Source: Neuropharmacology - November 26, 2018 Category: Drugs & Pharmacology Authors: Li JM, Liu LL, Su WJ, Wang B, Zhang T, Zhang Y, Jiang CL Tags: Neuropharmacology Source Type: research
Oleoylethanolamide restores alcohol-induced inhibition of neuronal proliferation and microglial activity in striatum.
seca F, Suárez J Abstract Previous findings demonstrate a homeostatic role for oleoylethanolamide (OEA) signaling in the ethanol-related neuroinflammation and behavior. However, extensive research is still required in order to unveil the effects of OEA on a number of neurobiological functions such as adult neurogenesis, cell survival and resident neuroimmunity that become notably altered by alcohol. Daily consumption of ethanol (10%) for 2 weeks (6.3±1.1 g/kg/day during last 5 days) caused hypolocomotor activity in rats. This effect appears to rely on central signaling mechanisms given that alcohol i...
Source: Neuropharmacology - November 26, 2018 Category: Drugs & Pharmacology Authors: Rivera P, Silva-Peña D, Blanco E, Vargas A, Arrabal S, Serrano A, Pavón FJ, Bindila L, Lutz B, Rodríguez de Fonseca F, Suárez J Tags: Neuropharmacology Source Type: research
Early memory consolidation window enables drug induced state-dependent memory.
ute;dez-Rattoni F Abstract It is well established that newly acquired information is stabilized over time by processes underlying memory consolidation, these events can be impaired by many drug treatments administered shortly after learning. The consolidation hypothesis has been challenged by a memory integration hypothesis, which suggests that the processes underlying new memories are vulnerable to incorporation of the neurobiological alterations induced by amnesic drugs generating a state-dependent memory. The present experiments investigated the effects of amnesic drugs infused into the insular cortex of male W...
Source: Neuropharmacology - November 25, 2018 Category: Drugs & Pharmacology Authors: Osorio-Gómez D, Saldivar-Mares KS, Perera-López A, McGaugh JL, Bermúdez-Rattoni F Tags: Neuropharmacology Source Type: research
Pharmacological classification of centrally acting drugs using EEG in freely moving rats: An old tool to identify new atypical dopamine uptake inhibitors.
Abstract Atypical dopamine uptake inhibitors (DUIs) bind to the dopamine transporter and inhibit the reuptake of dopamine but have lower abuse potential than psychostimulants. Several atypical DUIs can block abuse-related effects of cocaine and methamphetamine, thus making them potential medication candidates for psychostimulant use disorders. The aim of the current study is to establish an in-vivo assay using EEG for the rapid identification of atypical DUIs with potential for medication development. The typical DUIs cocaine and methylphenidate dose-dependently decreased the power of the alpha, beta, and gamma ba...
Source: Neuropharmacology - November 24, 2018 Category: Drugs & Pharmacology Authors: Zanettini C, Scaglione A, Keighron JD, Giancola JB, Lin SC, Newman AH, Tanda G Tags: Neuropharmacology Source Type: research
Distinct influence of COX-1 and COX-2 on neuroinflammatory response and associated cognitive deficits during high altitude hypoxia.
Abstract High-altitude hypoxia (HH) causes a spectrum of pathophysiological effects, including headaches, gliovascular dysfunction, and cognitive slowing. Previous studies have shown arachidonic acid (AA) metabolism due to cyclooxygenase (COX) activity before clinical manifestations in many diseases. AA metabolites, including COXs and prostaglandin E2 (PGE2), are well known immunomodulators. However, the relative contribution of COX-2 and COX-1 isoforms in the downstream proinflammatory responses and cognitive deficit in HH remains unknown. In the present study, AA metabolism via the COX pathway was investigated i...
Source: Neuropharmacology - November 23, 2018 Category: Drugs & Pharmacology Authors: Chauhan G, Roy K, Kumar G, Kumari P, Alam S, Kishore K, Panjwani U, Ray K Tags: Neuropharmacology Source Type: research
Neuro-metabolite profiles of rodent models of psychiatric dysfunctions characterised by MR spectroscopy.
Abstract Neuroimaging endophenotypes in animal models provide an objective and translationally-relevant alternative to cognitive/behavioral traits in human psychopathologies. Metabolic alterations, such as those involved in the glutamate-cycle, have been proposed to play a preponderant role in both depression and schizophrenia. Chronic Mild Unpredictable Stress (CMUS) and sub-chronic administration of NMDA receptor antagonist generate animal models of depression and schizophrenia, respectively. The models are based on etiologically-relevant factors related to the induction and support of these psychopathologies. T...
Source: Neuropharmacology - November 22, 2018 Category: Drugs & Pharmacology Authors: Sekar S, Grandjean J, Garnell JF, Willems R, Duytschaever H, Seramani S, Su H, Ver Donck L, Bhakoo KK Tags: Neuropharmacology Source Type: research
Partial restoration of physiological UP-state activity by GABA pathway modulation in an acute brain slice model of epilepsy.
Abstract In addition to reducing seizures, anti-epileptic treatments should preserve physiological network activity. Here, we used a thalamocortical slice preparation displaying physiological slow oscillations to investigate the effects of anticonvulsant drugs on physiological activity and epileptiform activity in two pharmacological epilepsy models. Thus, we compared the effects of GABA pharmacology on spontaneous physiological and pathological events in slices of the mouse barrel cortex. We show that both reducing inhibition using GABAAR blockers and enhancing excitation by lowering Mg2+ concentration allow for ...
Source: Neuropharmacology - November 22, 2018 Category: Drugs & Pharmacology Authors: Koerling AL, Fuchsberger T, Paulsen O, Hay YA Tags: Neuropharmacology Source Type: research
Zinc reduces antiseizure activity of neurosteroids by selective blockade of extrasynaptic GABA-A receptor-mediated tonic inhibition in the hippocampus.
Abstract Zinc is an abundant trace metal in the hippocampus nerve terminals. Previous studies demonstrate the ability of zinc to selectively block neurosteroid-sensitive, extrasynaptic GABA-A receptors in the hippocampus (Carver et al, 2016). Here we report that zinc prevents the seizure protective effects of the synthetic neurosteroid ganaxolone (GX) in an experimental model of epilepsy. GABA-gated and tonic currents were recorded from dissociated dentate gyrus granule cells (DGGCs), CA1 pyramidal cells (CA1PCs), and hippocampal slices from adult mice. Antiseizure effects of GX and the reversal of these effects b...
Source: Neuropharmacology - November 21, 2018 Category: Drugs & Pharmacology Authors: Chuang SH, Reddy DS Tags: Neuropharmacology Source Type: research
Mechanical allodynia and enhanced responses to capsaicin are mediated by PI3K in a paclitaxel model of peripheral neuropathy.
Abstract Paclitaxel chemotherapy treatment often leads to neuropathic pain resistant to available analgesic treatments. Recently spinal Toll-like receptor 4 (TLR4) and the transient receptor potential cation channel subfamily V member 1 (TRPV1) were identified to be involved in the pro-nociceptive effect of paclitaxel. The aim of this study was to investigate the role of phosphatidylinositol 3-kinase (PI3K) and serine/threonine kinases in this process, with the use of their antagonists (wortmannin, LY-294002 and staurosporine). The single paclitaxel administration (8 mg/kg i.p.) in mice induced robust mechanical a...
Source: Neuropharmacology - November 21, 2018 Category: Drugs & Pharmacology Authors: Adamek P, Heles M, Palecek J Tags: Neuropharmacology Source Type: research
Graphene quantum dots inhibit T cell-mediated neuroinflammation in rats.
Abstract We investigated the therapeutic capacity of nano-sized graphene sheets, called graphene quantum dots (GQD), in experimental autoimmune encephalomyelitis (EAE), an animal model of immune-mediated central nervous system (CNS) damage. Intraperitoneally administered GQD (10 mg/kg/day) accumulated in the lymph node and CNS cells of Dark Agouti rats in which EAE was induced by immunization with spinal cord homogenate in complete Freund's adjuvant. GQD significantly reduced clinical signs of EAE when applied throughout the course of the disease (day 0-32), while the protection was less pronounced if the treatm...
Source: Neuropharmacology - November 21, 2018 Category: Drugs & Pharmacology Authors: Tosic J, Stanojevic Z, Vidicevic S, Isakovic A, Ciric D, Martinovic T, Kravic-Stevovic T, Bumbasirevic V, Paunovic V, Jovanovic S, Todorovic-Markovic B, Markovic Z, Danko M, Micusik M, Spitalsky Z, Trajkovic V Tags: Neuropharmacology Source Type: research
Neuroprotection by cannabidiol and hypothermia in a piglet model of newborn hypoxic-ischemic brain damage.
CONCLUSIONS: cannabidiol administration after hypoxia-ischemia in piglets offers some neuroprotective effects but the combination of cannabidiol and hypothermia shows some additive effect leading to more complete neuroprotection than cannabidiol or hypothermia alone. PMID: 30468796 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - November 20, 2018 Category: Drugs & Pharmacology Authors: Barata L, Arruza L, Rodríguez MJ, Aleo E, Vierge E, Criado E, Sobrino E, Vargas C, Ceprián M, Gutiérrez-Rodríguez A, Hind W, Martínez-Orgado J Tags: Neuropharmacology Source Type: research
Lipopolysaccharide-induced depressive-like, anxiogenic-like and hyperalgesic behavior is attenuated by acute administration of α-(phenylselanyl) acetophenone in mice.
Lipopolysaccharide-induced depressive-like, anxiogenic-like and hyperalgesic behavior is attenuated by acute administration of α-(phenylselanyl) acetophenone in mice. Neuropharmacology. 2018 Nov 20;: Authors: Sabedra Sousa FS, Birmann PT, Bampi SR, Balaguez R, Alves D, Leite MR, Nogueira CW, Brüning CA, Savegnago L Abstract The lipopolysaccharide (LPS) is an endotoxin derived from gram-negative bacteria, which induces inflammation. The aims of this study were to evaluate the possible α-(phenylselanyl) acetophenone (PSAP) activity in reducing comorbid hyperalgesia, depressive-like and ...
Source: Neuropharmacology - November 20, 2018 Category: Drugs & Pharmacology Authors: Sabedra Sousa FS, Birmann PT, Bampi SR, Balaguez R, Alves D, Leite MR, Nogueira CW, Brüning CA, Savegnago L Tags: Neuropharmacology Source Type: research
The high efficacy of muscarinic M4 receptor in D1 medium spiny neurons reverses striatal hyperdopaminergia.
Abstract The opposing action of dopamine and acetylcholine has long been known to play an important role in basal ganglia physiology. However, the quantitative analysis of dopamine and acetylcholine signal interaction has been difficult to perform in the native context because the striatum comprises mainly two subtypes of medium-sized spiny neurons (MSNs) on which these neuromodulators exert different actions. We used biosensor imaging in live brain slices of dorsomedial striatum to monitor changes in intracellular cAMP at the level of individual MSNs. We observed that the muscarinic agonist oxotremorine decreases...
Source: Neuropharmacology - November 20, 2018 Category: Drugs & Pharmacology Authors: Nair AG, Castro LRV, El Khoury M, Gorgievski V, Giros B, Tzavara ET, Hellgren-Kotaleski J, Vincent P Tags: Neuropharmacology Source Type: research
Molecular basis involved in the blocking effect of antidepressant metergoline on C-type inactivation of Kv1.4 channel.
Abstract Voltage-gated potassium channels (VGKCs) are transmembrane ion channels specific for potassium. Currently there are nine kinds of VGKCs. Kv1.4 is one of shaker-related potassium channels. It is a representative alpha subunit of potassium channels that can inactivate A type-currents, leading to N pattern inactivation. Inactivation of Kv channels plays an important role in shaping electrical signaling properties of neuronal and muscular cells. The shape of N pattern inactivation can be modified by removing the N-terminal (NT) domain which results in non-inactivated currents and C pattern inactivation. In a ...
Source: Neuropharmacology - November 19, 2018 Category: Drugs & Pharmacology Authors: Bai HW, Eom S, Yeom HD, Nguyen KVA, Lee J, Sohn SO, Lee JH Tags: Neuropharmacology Source Type: research
Differential effect of amphetamine over the corticotropin-releasing factor CRF2 receptor, the orexin OX1 receptor and the CRF2-OX1 heteroreceptor complex.
nco R Abstract Stress is one of the factors underlying drug seeking behavior that often goes in parallel with loss of appetite. We here demonstrate that orexin 1 receptors (OX1R) may form heteromeric complexes with the corticotropin releasing factor CRF2 receptor. Two specific features of the heteromer were a cross-antagonism and a blockade by CRF2 of OX1R signaling. In cells expressing one of the receptors, agonist-mediated signal transduction mechanisms were potentiated by amphetamine. Sigma 1 (σ1) and 2 (σ2) receptors are targets of drugs of abuse and, despite sharing a similar name, the two recepto...
Source: Neuropharmacology - November 19, 2018 Category: Drugs & Pharmacology Authors: Navarro G, Medrano M, Aguinaga D, Vega-Quiroga I, Lillo A, Jiménez J, Casanovas M, Canela EI, Mallol J, Gysling K, Franco R Tags: Neuropharmacology Source Type: research
Amyloid- ß promotes neurotoxicity by Cdk5-induced p53 stabilization.
Amyloid-ß promotes neurotoxicity by Cdk5-induced p53 stabilization. Neuropharmacology. 2018 Nov 16;: Authors: Lapresa R, Agulla J, Sánchez-Morán I, Zamarreño R, Prieto E, Bolaños JP, Almeida A Abstract Neurodegeneration in selective brain areas underlies the pathology of Alzheimer's disease (AD). Although oligomeric amyloid-β (Aβ) plays a central role in the AD pathogenesis, the mechanism of neuronal loss in response to Aβ remains elusive. The p53 tumor suppressor protein, a key regulator of cell apoptosis, has been described to accumulate in affected b...
Source: Neuropharmacology - November 16, 2018 Category: Drugs & Pharmacology Authors: Lapresa R, Agulla J, Sánchez-Morán I, Zamarreño R, Prieto E, Bolaños JP, Almeida A Tags: Neuropharmacology Source Type: research
Neuroprotective effect of l-serine against white matter demyelination by harnessing and modulating inflammation in mice.
This study was designed to evaluate the neuroprotective effect of l-serine and the underlying mechanisms against the demyelinating injury of white matter. A model of focal demyelinating lesions (FDL) was established using the two-point stereotactic injection of 0.25% lysophosphatidylcholine (LPC, 10 μg per point) into the corpus callosum of mice. Mice were then intraperitoneally injected with one of three doses of l-serine (114, 342, or 1026 mg/kg) 2 h after FDL, and then twice daily for the next five days. Behavior tests and histological analysis were assessed for up to twenty-eight days post-FDL induction. Elect...
Source: Neuropharmacology - November 16, 2018 Category: Drugs & Pharmacology Authors: Wang G, Ding L, Gao C, Zhang N, Gan D, Sun Y, Xu L, Luo Q, Jiang Z Tags: Neuropharmacology Source Type: research
Opioid system modulators buprenorphine and samidorphan alter behavior and extracellular neurotransmitter concentrations in the Wistar Kyoto rat.
Abstract Approximately two-thirds of major depressive disorder (MDD) patients do not respond adequately to current therapies. BUP/SAM (ALKS 5461), a combination of buprenorphine (BUP) and samidorphan (SAM), is a novel opioid system modulator in development as an adjunct treatment for MDD. Using a rat strain (Wistar Kyoto rat) that is predisposed to stress and has an inadequate response to selective serotonin reuptake inhibitors (SSRIs), we investigated the effect of BUP and SAM, individually and in combination, in established nonclinical assays used to study antidepressants (the forced swim test, FST) and anxiolyt...
Source: Neuropharmacology - November 15, 2018 Category: Drugs & Pharmacology Authors: Smith KL, Cunningham JI, Eyerman DJ, Dean RL, Deaver DR, Sanchez C Tags: Neuropharmacology Source Type: research
Evaluation of ultrasonic vocalizations in a neurodevelopmental model of schizophrenia during the early life stages of rats.
Abstract In an animal neurodevelopmental model of schizophrenia, we investigated ultrasonic communication and social behavior in male and female rats. Pregnant dams were treated with methylazoxymethanol acetate (MAM; 22 mg/kg) at 17 days of gestation. First, we examined the ultrasonic vocalizations (USVs) emitted by 8-day-old pups isolated from their mothers and placed in a familiar or an unfamiliar environment. Second, we assessed tickling-induced USVs, social play (SP) behavior and accompanying USVs in 30-day-old juveniles. Independent of the prenatal treatment, sex differences were noted at both ages. In the ...
Source: Neuropharmacology - November 15, 2018 Category: Drugs & Pharmacology Authors: Potasiewicz A, Holuj M, Piotrowska D, Zajda K, Wojcik M, Popik P, Nikiforuk A Tags: Neuropharmacology Source Type: research
Oxytocin prevents the increase of cocaine-related responses produced by social defeat.
In conclusion, the long-lasting effects of RSD are counteracted by administering OXT prior to stress, and changes in BDNF expression may underlie these protective effects. PMID: 30448423 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - November 15, 2018 Category: Drugs & Pharmacology Authors: Ferrer-Pérez C, Castro-Zavala A, Luján MÁ, Filarowska J, Ballestín R, Miñarro J, Valverde O, Rodríguez-Arias M Tags: Neuropharmacology Source Type: research
Ultrasonic vocalizations as a tool in studying emotional states in rodent models of social behavior and brain disease.
Abstract Rodents emit ultrasonic vocalizations (USVs) to communicate the presence of positive or negative emotional states and to coordinate social interactions. On this basis, USVs are increasingly being used as a behavioral readout in rodent studies of affect, motivation and social behavior. Notably, several investigations have demonstrated that rodents emit USVs when tested in experimental paradigms that are used in preclinical studies of psychiatric and neurological diseases. Moreover, it has been shown that calling behavior may be influenced by genetic and/or environmental factors (i.e., stress), early rearin...
Source: Neuropharmacology - November 13, 2018 Category: Drugs & Pharmacology Authors: Simola N, Granon S Tags: Neuropharmacology Source Type: research
Crosstalk between Receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCR) in the brain: focus on heteroreceptor complexes and related functional neurotrophic effects.
rdo N Abstract Neuronal events are regulated by the integration of several complex signaling networks in which G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) are considered key players of an intense bidirectional cross-communication in the cell, generating signaling mechanisms that, at the same time, connect and diversify the traditional signal transduction pathways activated by the single receptor. For this receptor-receptor crosstalk, the two classes of receptors form heteroreceptor complexes resulting in RTKs transactivation and in growth-promoting signals. In this review, we describe ...
Source: Neuropharmacology - November 13, 2018 Category: Drugs & Pharmacology Authors: Di Liberto V, Mudò G, Belluardo N Tags: Neuropharmacology Source Type: research
Transcranial direct current stimulation induces hippocampal metaplasticity mediated by brain-derived neurotrophic factor.
Abstract Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique used to modulate neuronal excitability via externally applied electric fields. Despite the positive effects of tDCS in a wide range of neurological disorders in humans, its mechanism of action remains poorly understood. Here we investigated cellular and molecular mechanisms underlying the aftereffects of anodal tDCS on the induction of long-term potentiation (LTP), a cellular correlate of learning and memory, at Schaffer collateral-CA1 synapses. We found that hippocampal CA1 LTP was enhanced in slices from rats su...
Source: Neuropharmacology - November 12, 2018 Category: Drugs & Pharmacology Authors: Yu TH, Wu YJ, Chien ME, Hsu KS Tags: Neuropharmacology Source Type: research
Inhibition of N-acylethanolamine acid amidase reduces nicotine-induced dopamine activation and reward.
Abstract Tobacco smoke is the leading preventable cause of death in the world and treatments aimed to increase success rate in smoking cessation by reducing nicotine dependence are sought. Activation of peroxisome proliferator-activated receptor-alpha (PPARα) by synthetic or endogenous agonists was shown to suppress nicotine-induced activation of mesolimbic dopamine system, one of the major neurobiological substrates of nicotine dependence, and nicotine-seeking behavior in rats and monkeys. An alternative indirect way to activate PPARα is inhibition of N-acylethanolamine acid amidase (NAAA), one of the...
Source: Neuropharmacology - November 12, 2018 Category: Drugs & Pharmacology Authors: Sagheddu C, Scherma M, Congiu M, Fadda P, Carta G, Banni S, Wood JT, Makriyannis A, Malamas MS, Pistis M Tags: Neuropharmacology Source Type: research
Concomitant THC and stress adolescent exposure induces impaired fear extinction and related neurobiological changes in adulthood.
errendero F Abstract Δ9-tetrahydrocannabinol (THC) consumption during adolescence is reported to be a risk factor for the appearance of psychiatric disorders later in life. The interaction between genetic or environmental events and cannabinoid exposure in the adolescent period can also contribute to exacerbate behavioural deficits in adulthood. Here we investigate the effects of THC treatment as well as the consequences of concomitant THC and stress exposure during adolescence in the extinction of fear memory in adult mice. Adolescent mice treated with THC and exposed to stress exhibit impaired cued fear ex...
Source: Neuropharmacology - November 12, 2018 Category: Drugs & Pharmacology Authors: Saravia R, Ten-Blanco M, Julià-Hernández M, Gagliano H, Andero R, Armario A, Maldonado R, Berrendero F Tags: Neuropharmacology Source Type: research
Liraglutide and a lipidized analog of prolactin-releasing peptide show neuroprotective effects in a mouse model of β-amyloid pathology.
Liraglutide and a lipidized analog of prolactin-releasing peptide show neuroprotective effects in a mouse model of β-amyloid pathology. Neuropharmacology. 2018 Nov 11;: Authors: Holubová M, Hrubá L, Popelová A, Bencze M, Pražienková V, Gengler S, Kratochvílová H, Haluzík M, Železná B, Kuneš J, Hölscher C, Maletínská L Abstract Obesity and type 2 diabetes mellitus (T2DM) are important risk factors for Alzheimer's disease (AD). Drugs originally developed for T2DM treatment, e.g., analog of glucagon-like peptide 1 li...
Source: Neuropharmacology - November 11, 2018 Category: Drugs & Pharmacology Authors: Holubová M, Hrubá L, Popelová A, Bencze M, Pražienková V, Gengler S, Kratochvílová H, Haluzík M, Železná B, Kuneš J, Hölscher C, Maletínská L Tags: Neuropharmacology Source Type: research
GPR37 and GPR37L1 differently interact with dopamine 2 receptors in live cells.
Abstract Receptor-receptor interactions are essential to fine tune receptor responses and new techniques enable closer characterization of the interactions between involved proteins directly in the plasma membrane. Fluorescence cross-correlation spectroscopy (FCCS), which analyses concurrent movement of bound molecules with single-molecule detection limit, was here used to, in live N2a cells, study interactions between the Parkinson's disease (PD) associated orphan receptor GPR37, its homologue GPR37L1, and the two splice variants of the dopamine 2 receptor (D2R). An interaction between GPR37 and both splice forms...
Source: Neuropharmacology - November 10, 2018 Category: Drugs & Pharmacology Authors: Hertz E, Terenius L, Vukojević V, Svenningsson P Tags: Neuropharmacology Source Type: research
Ethanol and a rapid-acting antidepressant produce overlapping changes in exon expression in the synaptic transcriptome.
Abstract Alcohol use disorder (AUD) and major depressive disorder (MDD) are prevalent, debilitating, and highly comorbid disorders. The molecular changes that underlie their comorbidity are beginning to emerge. For example, recent evidence showed that acute ethanol exposure produces rapid antidepressant-like biochemical and behavioral responses. Both ethanol and fast-acting antidepressants block N-methyl-D-aspartate receptor (NMDAR) activity, leading to synaptic changes and long-lasting antidepressant-like behavioral effects. We used RNA sequencing to analyze changes in the synaptic transcriptome after acute treat...
Source: Neuropharmacology - November 9, 2018 Category: Drugs & Pharmacology Authors: Wolfe SA, Farris SP, Mayfield JE, Heaney CF, Erickson EK, Harris RA, Mayfield RD, Raab-Graham KF Tags: Neuropharmacology Source Type: research
Arrestin recruitment and signaling by G protein-coupled receptor heteromers.
Abstract G protein-coupled receptors (GPCR) have a long history of being considered a prime target for drug development to treat a plethora of diseases and disorders. In fact in 1827, the first approved therapeutic in the United States was morphine, a drug that targets a GPCR, namely the mu opioid receptor. However, with the rise in biologics over the last two decades, the market share of small molecules targeting GPCRs has declined. Still, two phenomena concerning GPCR pharmacology, specifically heteromerization and biased signaling, have bolstered new interests in this particular class of drug targets. Heteromer...
Source: Neuropharmacology - November 9, 2018 Category: Drugs & Pharmacology Authors: Mores KL, Cassell RJ, van Rijn RM Tags: Neuropharmacology Source Type: research
Synergistic effect of aripiprazole and escitalopram in increasing serotonin but not norepinephrine neurotransmission in the rat hippocampus.
This study investigated how aripiprazole, escitalopram and their combination affect the net effect of 5-HT and NE neurotransmission in the rat hippocampus. Electrophysiological recordings of hippocampus CA3 pyramidal neurons were conducted in anaesthetized Sprague-Dawley rats after 2- and 14-day administration regimens. Aripiprazole and escitalopram (2 and 5 mg/kg/day, respectively) were delivered alone or in combination through subcutaneous injections and implanted osmotic minipumps, respectively. Overall neurotransmission of 5-HT and NE were assessed by determining possible enhancements in tonic activation of 5-HT1A rece...
Source: Neuropharmacology - November 8, 2018 Category: Drugs & Pharmacology Authors: Ebrahimzadeh M, El Mansari M, Blier P Tags: Neuropharmacology Source Type: research
Therapeutic impacts of environmental enrichment: Neurobiological mechanisms informing molecular targets for enviromimetics.
an AJ PMID: 30408485 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - November 5, 2018 Category: Drugs & Pharmacology Authors: Kelly Á, Hannan AJ Tags: Neuropharmacology Source Type: research
Neuroprotective action of diazepam at very low and moderate doses in Alzheimer's disease model rats.
Abstract Early manifestations of Alzheimer's disease (AD) include neuroinflammation, disrupted neurotransmission and cognitive deficits. Impairment of the GABAergic system is essentially involved in the pathogenesis of AD. Traditionally, agonists of GABAA receptors at doses above 1 mg/kg are known to possess memory impairing effects. However, we have previously found that GABAA receptor GABA site ligand muscimol at very low doses acted contrary - enhanced spatial learning/memory, as well as prevented neuroinflammation and augmented neurotransmission in AD model rats. Therefore, in the present study we focused on t...
Source: Neuropharmacology - November 5, 2018 Category: Drugs & Pharmacology Authors: Pilipenko V, Narbute K, Pupure J, Rumaks J, Jansone B, Klusa V Tags: Neuropharmacology Source Type: research
Enhancement of synaptic plasticity and reversal of impairments in motor and cognitive functions in a mouse model of Angelman Syndrome by a small neurogenic molecule, NSI-189.
Abstract NSI-189 Phosphate, (4-benzylpiperazin-1-yl)-[2-(3-methyl-butylamino)pyridin-3-yl] methanone is a new chemical entity under development for the treatment of MDD, based upon preclinical data demonstrating stimulation of neurogenesis of human hippocampus-derived neural stem cells in vitro and in mouse hippocampus in vivo. Previous studies have examined the tolerability and efficacy of NSI-189 for treating major depressive disorder (MDD). NSI-189 has shown significant potential as a treatment for MDD, with concurrent improvement of a cognition scale in a small double-blind, placebo-controlled study. The curre...
Source: Neuropharmacology - November 5, 2018 Category: Drugs & Pharmacology Authors: Liu Y, Johe K, Sun J, Hao X, Wang Y, Bi X, Baudry M Tags: Neuropharmacology Source Type: research
Heterosynaptic modulation in the paraventricular nucleus of the hypothalamus.
Abstract The stress response-originally described by Hans Selye as "the nonspecific response of the body to any demand made upon it"-is chiefly mediated by the hypothalamic-pituitary-adrenal (HPA) axis and is activated by diverse sensory stimuli that inform threats to homeostasis. The diversity of signals regulating the HPA axis is partly achieved by the complexity of afferent inputs that converge at the apex of the HPA axis: this apex is formed by a group of neurosecretory neurons that synthesize corticotropin-releasing hormone (CRH) in the paraventricular nucleus of the hypothalamus (PVN). The afferent...
Source: Neuropharmacology - November 5, 2018 Category: Drugs & Pharmacology Authors: Sunstrum JK, Inoue W Tags: Neuropharmacology Source Type: research
Prosocial effects of an oxytocin metabolite, but not synthetic oxytocin receptor agonists, in a mouse model of autism.
Abstract Currently, there are no established pharmaceutical strategies that effectively treat social deficits in autism spectrum disorder (ASD). Oxytocin, a neurohormone that plays a role in multiple types of social behaviors, has been proposed as a possible therapeutic against social impairment and other symptoms in ASD. However, from the standpoint of pharmacotherapy, oxytocin has several liabilities as a standard clinical treatment, including rapid metabolism, low brain penetrance, and activity at the vasopressin (antidiuretic hormone) receptors. The present studies describe findings from a preclinical screenin...
Source: Neuropharmacology - November 3, 2018 Category: Drugs & Pharmacology Authors: Moy SS, Teng BL, Nikolova VD, Riddick NV, Simpson CD, Van Deusen A, Janzen WP, Sassano MF, Pedersen CA, Jarstfer MB Tags: Neuropharmacology Source Type: research
Conditioned media from AICAR-treated skeletal muscle cells increases neuronal differentiation of adult neural progenitor cells.
Abstract Exercise has profound benefits for brain function in animals and humans. In rodents, voluntary wheel running increases the production of new neurons and upregulates neurotrophin levels in the hippocampus, as well as improving synaptic plasticity, memory function and mood. The underlying cellular mechanisms, however, remain unresolved. Recent research indicates that peripheral organs such as skeletal muscle, liver and adipose tissue secrete factors during physical activity that may influence neuronal function. Here we used an in vitro cell assay and proteomic analysis to investigate the effects of proteins...
Source: Neuropharmacology - November 1, 2018 Category: Drugs & Pharmacology Authors: Moon HY, Javadi S, Stremlau M, Yoon KJ, Becker B, Kang SU, Zhao X, van Praag H Tags: Neuropharmacology Source Type: research
Computation-guided analysis of paroxetine binding to hSERT reveals functionally important structural elements and dynamics.
In this study, by carrying out and analyzing the results of extensive and comparative molecular dynamics simulations while also re-evaluating the transport and binding properties of the thermostabilized constructs, we identified functionally important structural elements that are perturbed by these mutations, revealed unexpected dynamics in the central primary binding site of SERT, and uncovered a conceivable ambiguity in paroxetine's binding orientation. We propose that the favored entropy contribution plays a significant role in paroxetine's extraordinarily high affinity for SERT. Our findings lay the foundation for futu...
Source: Neuropharmacology - October 31, 2018 Category: Drugs & Pharmacology Authors: Abramyan AM, Slack RD, Meena S, Davis BA, Newman AH, Singh SK, Shi L Tags: Neuropharmacology Source Type: research
Comparison of the behavioral responses induced by phenylalkylamine hallucinogens and their tetrahydrobenzodifuran ("FLY") and benzodifuran ("DragonFLY") analogs.
Comparison of the behavioral responses induced by phenylalkylamine hallucinogens and their tetrahydrobenzodifuran ("FLY") and benzodifuran ("DragonFLY") analogs. Neuropharmacology. 2018 Oct 29;: Authors: Halberstadt AL, Chatha M, Stratford A, Grill M, Brandt SD Abstract In recent years, rigid analogues of phenylalkylamine hallucinogens have appeared as recreational drugs. Examples include 2-(8-bromo-2,3,6,7-tetrahydrobenzo[1,2-b:4,5-b']difuran-4-yl)ethan-1-amine (2C-B-FLY) and 1-(8-bromobenzo[1,2-b;4,5-b']difuran-4-yl)-2-aminopropane (Bromo-DragonFLY, DOB-DFLY). Although some rigid...
Source: Neuropharmacology - October 29, 2018 Category: Drugs & Pharmacology Authors: Halberstadt AL, Chatha M, Stratford A, Grill M, Brandt SD Tags: Neuropharmacology Source Type: research
S-ketamine reduces marble burying behaviour: involvement of ventromedial orbitofrontal cortex and AMPA receptors.
In conclusion, the reduction of MBB by S-ketamine strengthens its possible anti-compulsive effect. The vmOFC is involved in this S-ketamine effect, which is dependent on the activation of AMPA receptors. PMID: 30385254 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - October 29, 2018 Category: Drugs & Pharmacology Authors: Tosta CL, Silote GP, Fracalossi MP, Sartim AG, Andreatini R, Lourenço Joca SR, Beijamini V Tags: Neuropharmacology Source Type: research
Bradykinin B1 receptor contributes to interleukin-8 production and glioblastoma migration through interaction of STAT3 and SP-1.
Abstract Glioblastoma (GBM), the most aggressive brain tumor, has a poor prognosis due to the ease of migration to surrounding healthy brain tissue. Recent studies have shown that bradykinin receptors are involved in the progression of various cancers. However, the molecular mechanism and pathological role of bradykinin receptors remains unclear. We observed the expressions of two major bradykinin receptors, B1R and B2R, in two different human GBM cell lines, U87 and GBM8901. Cytokine array analysis showed that bradykinin increases the production of interleukin (IL)-8 in GBM via B1R. Higher B1R levels correlate wi...
Source: Neuropharmacology - October 23, 2018 Category: Drugs & Pharmacology Authors: Liu YS, Hsu JW, Lin HY, Lai SW, Huang BR, Tsai CF, Lu DY Tags: Neuropharmacology Source Type: research
Habenula-prefrontal resting-state connectivity in reactive aggressive men - A pilot study.
Abstract Disproportionate anger and reactive aggression in response to provocation are core symptoms of intermittent-explosive disorder (IED). Previous research shows a link between the propensity for aggression in healthy individuals and altered functioning of prefrontal-limbic and default-mode networks (DMN) at rest when no provocation is present. In a pilot study, we used resting-state functional magnetic resonance imaging to investigate the effects of pronounced reactive aggression in men, exemplified by IED, on the functional organization of resting-state brain networks including subcortical nodes such as the...
Source: Neuropharmacology - October 23, 2018 Category: Drugs & Pharmacology Authors: Gan G, Zilverstand A, Parvaz MA, Preston-Campbell RN, d'Oleire Uquillas F, Moeller SJ, Tomasi D, Goldstein RZ, Alia-Klein N Tags: Neuropharmacology Source Type: research
Development of the MAM model of schizophrenia in mice: Sex similarities and differences of hippocampal and prefrontal cortical function.
In this study, we report the establishment of the neurodevelopmental MAM model of schizophrenia in mice and compare the schizotypic-like characteristics and cognitive functions in both sexes. Pregnant mice were injected with methylazoxymethanol acetate (MAM) or saline on gestational day (GD) 16 (MAM-16) or 17 (MAM-17). Female MAM-16, but not MAM-17 treated mice exhibited enhanced hyperlocomotion after acute MK-801 administration, compared to saline treated mice. Male MAM-16, but not MAM-17, treated mice showed reduced pre-pulse inhibition of the acoustic startle reflex. Both male and female MAM-16 and MAM-17 treated mice e...
Source: Neuropharmacology - October 23, 2018 Category: Drugs & Pharmacology Authors: Chalkiadaki K, Velli A, Kyriazidis E, Stavroulaki V, Vouvoutsis V, Chatzaki E, Aivaliotis M, Sidiropoulou K Tags: Neuropharmacology Source Type: research
Apamin treatment accelerates equilibrium recovery and gaze stabilization in unilateral vestibular neurectomized cats: Cellular and behavioral aspects.
Abstract Sudden and complete unilateral loss of peripheral vestibular inputs evokes characteristic vestibular syndrome comprised of posturo-locomotor, oculomotor, vegetative and cognitive symptoms. Subsequently to the vestibular insult, a neurophysiological process called central vestibular compensation promotes the progressive restoration of the posture and balance. The modulation of the excitability of vestibular secondary neurons has been demonstrated to be a key process of this mechanism. However, the molecular mechanisms that support this modulatory process have thus far not been fully identified. The present...
Source: Neuropharmacology - October 23, 2018 Category: Drugs & Pharmacology Authors: Tighilet B, Leonard J, Mourre C, Chabbert C Tags: Neuropharmacology Source Type: research
Activation of trace amine-associated receptor 1 attenuates schedule-induced polydipsia in rats.
Abstract Trace Amine Associated Receptor 1 (TAAR1) is a novel pharmacological target. TAAR1 are well-documented to play a modulatory role in the dopaminergic system. In spite of a growing number of studies of TAAR1 effects, little is still known about the behavioral pharmacology of TAAR1 ligands, including effects of repeated TAAR1 agonist administration. The present study appears to be the first that estimated the action of TAAR1 agonists on schedule-induced polydipsia, a type of adjunctive behavior, which is considered to be useful for evaluating certain aspects of obsessive-compulsive and related disorders (OCD...
Source: Neuropharmacology - October 23, 2018 Category: Drugs & Pharmacology Authors: Sukhanov I, Dorotenko A, Dolgorukova A, Hoener CM, Gainetdinov RR, Bespalov Yu A Tags: Neuropharmacology Source Type: research
The novel psychoactive substance methoxetamine induces persistent behavioral abnormalities and neurotoxicity in rats.
Abstract Methoxetamine (MXE) is a novel psychoactive substance that can induce several short-term effects on emotional states and behavior. However, little is known about the persistent emotional and behavioral effects of MXE. Moreover, neurotoxic effects of MXE have been hypothesized, but never demonstrated in vivo. To clarify these issues, rats received repeated treatment with MXE every other day (0.1-0.5 mg/kg, i.p., × 5), and 7 days later they were challenged with MXE (0.1-0.5 mg/kg, i.p.). Behavioral effects of MXE were first evaluated by measuring emission of ultrasonic vocalizations and locomo...
Source: Neuropharmacology - October 23, 2018 Category: Drugs & Pharmacology Authors: Costa G, Serra M, Pintori N, Casu MA, Zanda MT, Murtas D, De Luca MA, Simola N, Fattore L Tags: Neuropharmacology Source Type: research
Drug-receptor kinetics and sigma-1 receptor affinity differentiate clinically evaluated histamine H3 receptor antagonists.
Abstract The histamine H3 receptor is a G protein-coupled receptor (GPCR) drug target that is highly expressed in the CNS, where it acts as both an auto- and hetero-receptor to regulate neurotransmission. As such, it has been considered as a relevant target in disorders as varied as Alzheimer's disease, schizophrenia, neuropathic pain and attention deficit hyperactivity disorder. A range of competitive antagonists/inverse agonists have progressed into clinical development, with pitolisant approved for the treatment of narcolepsy. Given the breadth of compounds developed and potential therapeutic indications, we as...
Source: Neuropharmacology - October 22, 2018 Category: Drugs & Pharmacology Authors: Riddy DM, Cook AE, Shackleford DM, Pierce TL, Mocaer E, Mannoury la Cour C, Sors A, Charman WN, Summers RJ, Sexton PM, Christopoulos A, Langmead CJ Tags: Neuropharmacology Source Type: research
Amphetamine enantiomers inhibit homomeric α7 nicotinic receptor through a competitive mechanism and within the intoxication levels in humans.
In conclusion, our data present new findings that implicate the α7 nAChR on the pharmacodynamics of ATS, which may be important for behavioral responses to these drugs, indicating a potential role for α7 nAChRs in ATS substance-use disorders. PMID: 30359640 [PubMed - as supplied by publisher] (Source: Neuropharmacology)
Source: Neuropharmacology - October 22, 2018 Category: Drugs & Pharmacology Authors: Garton DR, Ross SG, Maldonado-Hernández R, Quick M, Lasalde-Dominicci JA, Lizardi-Ortiz JE Tags: Neuropharmacology Source Type: research
Muscarinic receptors regulate auditory and prefrontal cortical communication during auditory processing.
Abstract Much of our understanding about how acetylcholine modulates prefrontal cortical (PFC) networks comes from behavioral experiments that examine cortical dynamics during highly attentive states. However, much less is known about how PFC is recruited during passive sensory processing and how acetylcholine may regulate connectivity between cortical areas outside of task performance. To investigate the involvement of PFC and cholinergic neuromodulation in passive auditory processing, we performed simultaneous recordings in the auditory cortex (AC) and PFC in awake head fixed mice presented with a white noise au...
Source: Neuropharmacology - October 20, 2018 Category: Drugs & Pharmacology Authors: James NM, Gritton HJ, Kopell N, Sen K, Han X Tags: Neuropharmacology Source Type: research