Mirror numbers activate quantity representations, but show no SNARC effect: A working memory explanation.

The Spatial-Numerical Association of Response Code (SNARC) effect refers to the finding that people respond to small numbers faster with the left hand and to large numbers faster with the right hand. This effect is often explained by hypothesizing that the mental representation of quantities has a spatial component: left to right in ascending order (Mental Number Line). Here we assess the relation between quantity and spatial representation by investigating mirror numbers.

[Dmt1]N/OFQ(1-13)-NH2: a potent nociceptin/orphanin FQ and opioid receptor universal agonist.

Background And Purpose: Intrathecally (i.t.) administered nociceptin/orphanin FQ (N/OFQ) evokes antinociceptive effects in rodents.

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial.

Background: Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services.

Methods/design: The Psychosis early Intervention and Assessment of Needs and Outcome (PIANO) trial is part of a larger research program (Genetics, Endophenotypes and Treatment: Understanding early Psychosis - GET UP) which aims to compare, at 9 months, the effectiveness of a multi-component psychosocial intervention versus treatment as usual (TAU) in a large epidemiologically based cohort of patients with FEP and their family members recruited from all public community mental health centers (CMHCs) located in two entire regions of Italy (Veneto and Emilia Romagna), and in the cities of Florence, Milan and Bolzano. The GET UP PIANO trial has a pragmatic cluster randomized controlled design.

[tBu-D-Gly5]NPS, a pure and potent antagonist of the neuropeptide S receptor: in vitro and in vivo studies.

Neuropeptide S (NPS) regulates various biological functions by selectively activating the NPS receptor (NPSR). Recently, the NPSR ligand [(t)Bu-D-Gly(5)]NPS was generated and in vitro characterized as a pure antagonist at the mouse NPSR. In the present study the pharmacological profile of [(t)Bu-D-Gly(5)]NPS has been investigated.

Behavioural phenotypic characterization of CD-1 mice lacking the neuropeptide S receptor.

Neuropeptide S (NPS) is the endogenous ligand of a previously orphan receptor now named NPSR. In the brain NPS regulates several biological functions including anxiety, arousal, locomotion, food intake, learning and memory, pain and drug abuse. Mice lacking the NPSR gene (NPSR(-/-)) represent an useful tool to investigate the neurobiology of the NPS/NPSR system.

Nociceptin/orphanin FQ receptor knockout rats: in vitro and in vivo studies.

Nociceptin/orphanin FQ (N/OFQ) regulates several biological functions via selective activation of the N/OFQ peptide (NOP) receptor. Recently knockout rats for the NOP receptor gene (NOP(-/-)) have been generated; these animals were used in the present study to investigate their emotional (open field, elevated plus maze, and forced swimming test), locomotor (drag and rotarod test), and nociceptive (plantar and formalin test) phenotypes in comparison with their NOP(+/+) littermates. In addition, N/OFQ sensitivity has been assessed in electrically stimulated vas deferens tissues taken from NOP(+/+) and NOP(-/-) rats.

Anti-inflammatory and analgesic effects displayed by peptides derived from PKI55 protein, an endogenous protein kinase C inhibitor.

We recently characterized the PKI55 protein as an endogenous protein kinase C (PKC) inhibitor and investigated, in vitro, the potential anti-inflammatory actions of its N-terminal peptides 1-16 (peptide 5), 1-8 (peptide 8) and 1-5 (peptide 9). We showed their ability to inhibit chemotaxis in human polymorphonuclear leukocytes activated by the N-formyl tripeptide for-Met-Leu-Phe-OMe. In this work, we evaluated the anti-inflammatory and the analgesic effects of the selected peptides by in vivo experiments carried out in the mouse.

Further studies on the pharmacological features of the nociceptin/orphanin FQ receptor ligand ZP120.

ZP120 is a nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) ligand. In previous studies, the effects of ZP120 were found to be sensitive to J-113397 in mouse tissues while resistant to UFP-101 in rat tissues. The aim of this study was to further investigate the ZP120 pharmacological profile using mouse and rat preparations, J-113397 and UFP-101, as well as NOP receptor knockout (NOP(-/-)) mice.

In vitro and in vivo pharmacological characterization of the neuropeptide s receptor antagonist [D-Cys(tBu)5]neuropeptide S.

Neuropeptide S (NPS) was identified as the endogenous ligand of an orphan receptor now referred to as the NPS receptor (NPSR). In the frame of a structure-activity study performed on NPS Gly5, the NPSR ligand [D-Cys(tBu)(5)]NPS was identified. [D-Cys(tBu)(5)]NPS up to 100 microM did not stimulate calcium mobilization in human embryonic kidney (HEK) 293 cells stably expressing the mouse NPSR; however, in a concentration-dependent manner, the peptide inhibited the stimulatory effects elicited by 10 and 100 nM NPS (pK(B), 6.

Neuropeptide S is a stimulatory anxiolytic agent: a behavioural study in mice.

Background And Purpose: Neuropeptide S (NPS) was recently identified as the endogenous ligand of an orphan receptor, now referred to as the NPS receptor. In vivo, NPS produces a unique behavioural profile by increasing wakefulness and exerting anxiolytic-like effects. In the present study, we further evaluated the effects of in vivo supraspinal NPS in mice.

In vitro and in vivo studies on UFP-112, a novel potent and long lasting agonist selective for the nociceptin/orphanin FQ receptor.

[(pF)Phe(4)Aib(7)Arg(14)Lys(15)]N/OFQ-NH(2) (UFP-112) has been designed as a novel ligand for the nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) by combining into the same peptide different chemical modifications reported to increase N/OFQ potency. In vitro data obtained in the electrically stimulated mouse vas deferens demonstrated that UFP-112 behaved as a high potency (pEC(50) 9.43) full agonist at the NOP receptor.

Altered anxiety-related behavior in nociceptin/orphanin FQ receptor gene knockout mice.

Studies showed that nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) agonists produce anxiolytic-like actions, while little is known about the effects of blockade of NOP receptor signaling in anxiety. To this aim, we investigated the behavioral phenotype of NOP receptor gene knockout mice (NOP(-/-)) in different assays. In the elevated plus-maze and light-dark box, NOP(-/-) mice displayed increased anxiety-related behavior.

Pharmacological characterization of the nociceptin/orphanin FQ receptor antagonist SB-612111 [(-)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol]: in vivo studies.

The excellent pharmacological profile displayed by the selective nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor antagonist SB-612111 [(-)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol] in vitro prompted us to investigate the actions of this compound in vivo. In the mouse tail withdrawal assay, SB-612111 given i.p.

Endogenous nociceptin/orphanin FQ signalling produces opposite spinal antinociceptive and supraspinal pronociceptive effects in the mouse formalin test: pharmacological and genetic evidences.

Nociceptin/orphanin FQ (N/OFQ) has been demonstrated to modulate nociceptive transmission via selective activation of N/OFQ peptide (NOP) receptors. Despite huge research efforts, the role(s) of the endogenous N/OFQ-NOP receptor system in pain processing remains incompletely understood. In the present study, we investigated the role of endogenous N/OFQ in the processing of tonic nociceptive input.

Ascorbic and 6-Br-ascorbic acid conjugates as a tool to increase the therapeutic effects of potentially central active drugs.

Ascorbic acid (AA) or 6-Br-ascorbate (BrAA) conjugation has been investigated as a tool to improve brain drug delivery by the Vitamin C transporter SVCT2. To this aim, the effects of AA- or BrAA-conjugation on drug affinity and uptake have been assessed in vitro, by using human retinal pigment epithelium (HRPE) cells, and compared in vivo on mice. Nipecotic, kynurenic and diclofenamic acids were chosen as model drugs.

[(pF)Phe4,Arg14,Lys15]N/OFQ-NH2 (UFP-102), a highly potent and selective agonist of the nociceptin/orphanin FQ receptor.

A novel ligand for the nociceptin/orphanin FQ (N/OFQ) receptor (NOP), [(pF)Phe(4),Arg(14),Lys(15)]N/OFQ-NH(2) (UFP-102), has been generated by combining in the N/OFQ-NH(2) sequence two chemical modifications, [Arg(14),Lys(15)] and [(pF)Phe(4)], that have been previously demonstrated to increase potency. In vitro, UFP-102 bound with high affinity to the human NOP receptor, showed at least 200-fold selectivity over classical opioid receptors, and mimicked N/OFQ effects in CHO(hNOP) cells, isolated tissues from various species, and mouse cortical synaptosomes releasing 5-hydroxytryptamine. UFP-102 showed similar maximal effects but higher potency (2- to 48-fold) relative to N/OFQ.

Antidepressant-like effects of the nociceptin/orphanin FQ receptor antagonist UFP-101: new evidence from rats and mice.

Receptor antagonist and knockout studies have demonstrated that blockade of signalling via nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) has antidepressant-like effects in mice submitted to the forced swimming test (FST). The aim of the present study was to explore further the antidepressant-like properties of the NOP antagonist UFP-101 in different species (mouse and rat) and using different assays [FST and tail suspension test (TST)], and to investigate the mechanism(s) involved in its actions.UFP-101 (10 nmol i.

Blockade of nociceptin/orphanin FQ-NOP receptor signalling produces antidepressant-like effects: pharmacological and genetic evidences from the mouse forced swimming test.

Nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the NOP receptor, regulates several central functions such as pain transmission, learning and memory, fear and anxiety and feeding and locomotor activity. It has been recently reported that NOP receptor antagonists induce antidepressant-like effects in the mouse forced swimming test (FST), i.e.

Pharmacological characterization of the novel nociceptin/orphanin FQ receptor ligand, ZP120: in vitro and in vivo studies in mice.

1 This study reports on the pharmacological characterization of ZP120, a novel ligand of the nociceptin/orphanin FQ (N/OFQ) peptide receptor, NOP. ZP120 is a structure inducing probes modified NOP ligand: Zealand Pharma proprietary SIP technology was used to increase the enzymatic stability and half-life of peptide. 2 In vitro, ZP120 mimicked the inhibitory effects of N/OFQ in the electrically stimulated mouse vas deferens, showing however higher potency (pEC(50) 8.

Pharmacological characterisation of [(pX)Phe4]nociceptin(1-13)NH2 analogues. 2. In vivo studies.

As part of a structure-activity study focused on the Phe(4) residue of nociceptin (NC) (1-13)NH(2), we identified two highly potent and selective agonists for the OP(4) receptor, [(pF)Phe(4)]NC(1-13)NH(2) and [(pNO(2))Phe(4)]NC(1-13)NH(2), whose in vitro pharmacological profiles have been described in the companion paper. In the present study, we investigated the actions of [(pF)Phe(4)]NC(1-13)NH(2) and compared it with those of NC(1-13)NH(2) in a battery of vivo assays. In the locomotor activity test in mice, 1 nmol NC(1-13)NH(2) given intracerebroventricularly (i.

[Nphe1,Arg14,Lys15]nociceptin-NH2, a novel potent and selective antagonist of the nociceptin/orphanin FQ receptor.

1. Nociceptin/orphanin FQ (N/OFQ) modulates several biological functions by activating a specific G-protein coupled receptor (NOP). Few molecules are available that selectively activate or block the NOP receptor.

[Arg(14),Lys(15)]nociceptin, a highly potent agonist of the nociceptin/orphanin FQ receptor: in vitro and in vivo studies.

The nociceptin (NC)/orphanin FQ analog, [Arg(14),Lys(15)]NC, has been recently demonstrated to behave as a potent agonist at the human recombinant NC receptors (OP(4)). In this study, we evaluated the pharmacological profile of [Arg(14),Lys(15)]NC in vitro on the native OP(4) receptors expressed in isolated tissues and in vivo in the locomotor activity and the tail-withdrawal assays in mice. On isolated tissues, [Arg(14),Lys(15)]NC mimicked the effects of NC, showing similar maximal effects but higher potencies (17-fold in the mouse vas deferens, 10-fold in the rat vas deferens, and about 5-fold in the guinea pig ileum and mouse colon).

Endogenous nociceptin signaling and stress-induced analgesia.

Nociceptin/orphanin FQ (NC) and its receptor (OP4) have been implicated in pain transmission. The aim of the present study was to investigate the role of the NC/OP4 system in stress-induced analgesia (SIA). The tail-withdrawal assay was performed in mice stressed by forced swimming in water at 15 degrees C (high severity swims) or 32 degrees C (low severity swims).

Characterization of the locomotor activity-inhibiting effect of nociceptin/orphanin FQ in mice.

Nociceptin/orphanin FQ (NC) modulates spontaneous locomotor activity (LA) in mice. NC applied intracerebroventricularly (i.c.

The nociceptin/orphanin FQ receptor antagonist, [Nphe1]NC(1-13)NH2, potentiates morphine analgesia.

Nociceptin/orphanin FQ (NC) and its receptor (OP4) represent a novel peptide/receptor system which has been implicated in the regulation of various central functions, including pain. The aim of the present study was to explore the involvement of the endogenous NC/OP4 system in the modulation of opioid analgesia using the selective OP4 receptor antagonist [Nphe1]NC(1-13)NH2. Experiments were performed in mice exposed to acute as well as chronic treatment with morphine.