Laboratory Investigation (2010) 90, 1628-1636; doi:10 1038/labinv

Laboratory Investigation (2010) 90, 1628-1636; doi:10.1038/labinvest.2010.158;

published online 23 August 2010″
“Periodic sharp wave complexes observed on an electroencephalographic recording and the presence of a 14-3-3 protein in the cerebrospinal Selleckchem CHIR-99021 fluid (CSF) are both included in the diagnostic criteria for the Creutzfeldt-Jakob disease (CJD) supplied by the World Health Organization; however, the presence or absence of the 14-3-3 protein in the CSF is sometimes difficult to discern on a western blot because of equivocal bands. The goal of this study was to establish a standard 14-3-3 protein assay and to determine the threshold level of a 14-3-3 protein that can be assayed by western blot. We searched for the most suitable isoform of the 14-3-3 protein to test for in protein assays, and the most sensitive antibody among four antibodies with PD0332991 an affinity for 14-3-3. We measured the levels of all 14-3-3 isoforms in 112 patients with CJD and in 100 patients with other diseases. We compared the performances of four different

antibodies. We carried out a semi-quantitative analysis of gamma-isoform levels using the LAS 3000 system, which was capable of producing a digital image from the luminescence on a western blot. We determined that the most suitable isoform of the 14-3-3 protein for conducting a standardized assay was the gamma-isoform. Among the four commercially available antibodies for this protein, the most sensitive and specific was 18647 (IBL, Japan). We report the high repeatability of the detection of the 14-3-3 protein by this antibody to the gamma-isoform, showing that western blot can be used for semi-quantitative

analysis. Laboratory Investigation (2010) 90, 1637-1644; Epacadostat molecular weight doi:10.1038/labinvest.2009.68; published online 9 August 2010″
“In this study, we investigated the involvement of dystrophin-associated proteins (DAPs) and their relationship with the perivascular basement membrane in the brains of mdx mice and controls at the age of 2 months. We analyzed (1) the expression of glial DAPs alpha-beta-dystroglycan (DG), alpha-syntrophin, aquaporin-4 (AQP4) water channel, Kir 4.1 and dystrophin isoform (Dp71) by immunocytochemistry, laser confocal microscopy, immunogold electron microscopy, immunoblotting and RT-PCR; (2) the ultrastructure of the basement membrane and expression of laminin and agrin; and (3) the dual immunofluorescence colocalization of AQP4/alpha-beta-DG, and of Kir 4.1/agrin.

“We previously showed conjugated linoleic acids (CLA) inhi

“We previously showed conjugated linoleic acids (CLA) inhibited TNF-alpha-induced monocyte (THP-1) adhesion to human umbilical vein endothelial cells (HUVEC) in vitro which involved an increase in platelet activating factor (PAF). Here we show adhesion molecule (ADM) regulation by fatty acids and the differing role of nuclear factor kappa B (NF-kappa B) activation in HUVEC and vascular smooth muscle cells (vSMC). CLA and omega-3 long-chain polyunsaturated fatty acids (PUFA) (FA) reduced TNF-alpha-induced expression of ADMs (intercellular AZD4547 clinical trial adhesion molecule-1

(ICAM-1); vascular cell adhesion molecule-1 (VCAM-1) but not E-selectin) on HUVEC and vSMC to different extents depending on FA type and concentration, cell type and method of analysis. I kappa B alpha phosphorylation in HUVEC and vSMC and transient transfection with NF-kappa

B-luciferase reporter plasmid (HUVEC only) indicated differential NF-kappa B involvement during FA modulation (cis-9, trans-11; trans-10, cis-12 and a 50:50 mix of both CLA isomers; eicosapentaenoic acid (EPA); docosahexaenoic acid (DHA)). TNF-a-induced ADM expression in both cell types by 2-10-fold. In HUVEC, CLA t10, c12 and CLA mix (50:50 mixture of CLA c9, t11 and t10, c12) and EPA and DHA reduced ICAM-I expression (15-35%) at 12.5, 25 and/or 50 mu M. VCAM-I expression SRT2104 in vivo was reduced by 25 mu M 00, c12 isomer and mix; omega-3 PUFA and other concentrations of CLA and TNF-a-induced E-selectin expression were unaffected. TNF alpha-induced inhibitor kappa B (I kappa B) phosphorylation was biphasic peaking at 5 min in both cell types and 60 and 120 min in HUVEC

and SMC, respectively. I kappa B alpha phosphorylation and NF-kappa B activity was reduced (29% and 30%, respectively) by 25 mu M CLA mix. n-3 PUFA did not reduce I kappa B alpha phosphorylation or NF-kappa B activity but reduced ADM expression. We show that n-3 PUFA and CLA reduce expression of ADM on HUVEC and vSMC. This reflected reduced adherence of monocytes to HUVEC previously reported by our group. Reduction of ICAM-1 and VCAM-1 protein expression by n-3 PUFA was less dependent on the NF-kappa B pathway than reduction by CLA which reflected the parallel attenuation of NF-kappa B activity. This indicated involvement of other SU5402 concentration transcription factors (i.e. AP-1) in the FA regulation of ADM expression and has, to our knowledge, not been previously reported. (C) 2007 Elsevier Ltd. All rights reserved.”
“The Epstein-Barr virus (EBV) genome is maintained as an extrachromosomal episome during latent infection of B lymphocytes. Episomal maintenance is conferred by the interaction of the EBV-encoded nuclear antigen 1 (EBNA1) with a tandem array of high-affinity binding sites, referred to as the family of repeats (FR), located within the viral origin of plasmid replication (OriP).

This structure of the early gene promoter might be selectively ma

This structure of the early gene promoter might be selectively maintained by allowing fast growth of the virus. With amino acid limitation, there exist finite optimal ratio of early/late gene promoter activity. (C) 2009 Elsevier Ltd. All rights reserved.”
“Repetitive transcranial magnetic stimulation (rTMS) has been increasingly evaluated as a therapeutic tool for the treatment of

depression, using various stimulation parameters and protocols. Heterogeneous results have been reported with regard to clinical outcome, at least partly due to the variety of procedures for buy NU7441 coil placement above the desired site of stimulation. This article reviews the strategies for coil positioning in the treatment of depression. Considering preliminary clinical evidence, neuronavigated rTMS appears desirable to treat

depression, compared to the standard targeting SHP099 cell line procedure (5 cm anterior to the motor cortex). Coil positioning strategy might improve in the future by taking into consideration the individual abnormalities revealed by functional neuroimaging data. (C) 2009 Elsevier Masson SAS. All rights reserved.”
“Tinnitus affects 10% of the population, its pathophysiology remains incompletely understood, and treatment is elusive. Both animal models and functional imaging data in tinnitus patients suggest that tinnitus is associated with increased neuronal activity, increased synchronicity and functional reorganisation in the auditory cortex. Therefore, targeted modulation of auditory cortex has Selleck VE-822 been proposed as a new therapeutic approach for chronic tinnitus. Repetitive

transcranial magnetic stimulation (rTMS), a non invasive method for modulation of cortical activity, has been applied in different ways in patients with chronic tinnitus. Single sessions of high-frequency rTMS over the temporal cortex have been used to transiently interfere with the intensity of tinnitus. Repeated sessions of low-frequency rTMS have been investigated as a treatment for tinnitus. Here, we review data from clinical trials and discuss potential neurobiological mechanisms with special focus on the relevance of the stimulation target and the method of TMS coil positioning. Different functional neuroimaging techniques are used for detecting tinnitus-related changes in brain activity. They converge in the finding of increased neuronal activity in the central auditory system, but they differ in the exact localisation of these changes, which in turn results in uncertainty about the optimal target for rTMS treatment. In this context, it is not surprising that the currently available studies do not demonstrate clear evidence for superiority of neuronavigational coil positioning. Further development of rTMS as a treatment for tinnitus will depend on a more detailed understanding of both the neuronal correlates of the different forms of tinnitus and of the neurobiological effects mediating the benefit of TMS on tinnitus perception. (C) 2009 Elsevier Masson SAS. All rights reserved.

When a single generalized seizure was elicited 10 min following

When a single generalized seizure was elicited 10 min following

phenytoin administration, average phenytoin brain dialysate levels were significantly lower (up to 45%) than those of control animals. During a self-sustained status epilepticus, phenytoin access to the site of seizure initiation tended to be lower in the early phase following drug administration, but reached control level 2 h later.

The data clearly demonstrate that seizure-induced alterations in BBB integrity and function do not increase extracellular brain levels of phenytoin in affected brain regions, but rather tend to decrease the eFT-508 ic50 free concentration of phenytoin in the extracellular compartment. (C) 2011 Elsevier Ltd. All rights reserved.”
“Nuclear factor E2 related Evofosfamide purchase factor-2 (Nrf2) transcription factor is one of the main regulators of intracellular redox balance and a sensor of oxidative and electrophilic stress. Low Nrf2 activity is usually associated with carcinogenesis, but Nrf2 is also considered as an oncogene because it increases survival of transformed cells. Because intracellular redox balance alterations :ire involved in both senescence and tumorigenesis, we investigated the impact of Nrf2 genetic deletion on cellular immortalization and life span of murine embryonic Fibroblasts. We report that Nrf2 genetic deletion promotes immortalization due to

an early loss of p53-dependent gene expression. However, compared with control cells, immortalized Nrf2-/- murine embryonic fibroblasts exhibited decreased growth, lower cycl in E levels, and impaired expression of NQO1 and cytochrome b(5) reductase. Moreover, SirT1 was also significantly reduced in immortalized Nrf2-/- murine embryonic fibroblasts, and these cells exhibited shorter life

span. Our results underscore the dual role of Nrf2 in protection against carcinogenesis and in the delay of cellular aging.”
“Two-pore-domain K(+) (K(2)P) channels are highly expressed in neurons and cardiac myocytes. In this JIB04 concentration study we investigated the potency of the antidepressant fluoxetine to inhibit brain and cardiac K(2)P channels, TREK-1, TASK-1 and THIK-1. Maximal sensitivity was detected for TREK-1, which was inhibited by 77% when expressed in HEK-293 cells and Xenopus oocytes. Alternative translation initiation (ATI) generates two different protein products from a single transcript of TREK-1. Electrophysiological analysis of two polypeptides engineered by mutagenesis (TREK-1[M53I], TREK-1[Delta N52]) revealed reduced current amplitude and K(+) selectivity of the truncated TREK-1 isoform. The sensitivity of TREK-1[Delta N52] to fluoxetine decreased by 70%, indicating that the first 52 amino acids are essential for TREK-1 sensitivity to this drug. (C) 2011 Elsevier Ltd. All rights reserved.”
“Werner syndrome is a premature aging disorder caused by mutations in a RecQ-like DNA helicase.

Transmission electron microscopy (TEM) revealed that the dissocia

Transmission electron microscopy (TEM) revealed that the dissociated HBcAg was able to re-associate into particles when the applied denaturing

agents were physically removed. In order to evaluate the potential of the Particles in capturing molecules, purified green fluorescent protein (GFP) was applied to the dissociated HBcAg for encapsidation. The HBcAg particles harbouring the GFP molecules were Purified using sucrose density gradient ultracentrifugation and analysed using native agarose gel electrophoresis and TEM. A method for the encapsidation of GFP in HBcAg particles which has the potential to Capture drugs or nucleic acids was established. (c) 2008 Elsevier B.V. All rights reserved.”
“Group I metabotropic glutamate receptors have been often implicated in various models of neuronal toxicity, however, the role played by the individual receptors and their putative mechanisms of action contributing to neurotoxicity or neuroprotection remain unclear. Here, E7080 purchase using primary cultures of rat cerebellar granule cells and mouse cortical neurons, we show that conditions

Tozasertib order of trophic deprivation increased mGlu1 expression which correlated with the developing cell death. The inhibition of mGlu1 expression by specific siRNA attenuated toxicity, while adenovirus-mediated overexpression of mGlu1 resulted in increased cell death, indicating a causal relationship between the level of receptor expression and neuronal survival. In pharmacological experiments selective mGlu1 antagonists failed to protect from mGlu1-induced cell death, instead. neuronal Survival was promoted by glutamate acting at mGlu1 receptors. Such properties are characteristics of a novel heterogeneous family of dependence receptors which control neuronal apoptosis. Our findings indicate that increased expression of mGlu1 in neurons creates a state of cellular dependence on the presence of its endogenous agonist glutamate. We propose a new role and a new mechanism for mGlu1 action. This receptor may play a crucial role in determining the fate of individual neurons during the development of the nervous system. (C) 2008 Elsevier Ltd. All rights reserved.”

stripe virus (RSV) is an important pathogen affecting rice production in subtropical and temperate regions. One-step real time RT-PCR methods using the TaqMan probe are described for quantitative detection of RSV in rice tissues and in Laodelphax striatellus Fallen, the small brown planthopper(SBPH). primers and probe for specific detection of RSV were designed within the conserved region identified within the coat protein (CP) gene sequence. A DNA fragment was amplified for mimicking the complementary RNA by PCR-based gene assembly, and was used for generation of standard RNA templates. A sensitivity assay showed that the detection limit of the assay was 20 copies, and the standard curve had a linear range from 20 to 2 x 10(5) copies, with good reproducibility.

This study now identifies two domains of VP24 required for inhibi

This study now identifies two domains of VP24 required for inhibition of IFN-beta-induced gene expression and PY-STAT1 nuclear accumulation. We demonstrate that loss of function correlates with BI-D1870 mouse loss of binding to KPN alpha proteins. Thus, the VP24 IFN antagonist function requires the ability of VP24 to interact with KPN alpha.”
“The central cholinergic system is involved in several cognitive functions such as attention, consciousness, learning and memory. Functional

imaging of this neurotransmitter system may provide novel opportunities in the diagnosis and evaluation of cognitive disorders. The aim of this study was to investigate the spatial and temporal activation patterns of muscarinic acetylcholine receptor (mAChR) stimulation in rat brain with pharmacological magnetic resonance imaging (phMRI). We performed blood Wortmannin research buy oxygenation level-dependent (BOLD) MRI and contrast-enhanced cerebral blood volume (CBV)-weighted MRI combined with injection of pilocarpine, a non-selective mAChR agonist. BOLD and CBV responses were assessed after pretreatment with methyl-scopolamine in order to block peripheral muscarinic effects. Region-of-interest analysis in individual animals and group-level independent component analysis failed to show significant BOLD signal changes following pilocarpine injection. However, with contrast-enhanced CBV-weighted MRI,

positive CBV responses were detected in the cerebral cortex, thalamus, and hippocampus whereas a negative about CBV response was observed in the striatum. Thus, pilocarpine-induced significant activation responses in brain regions that are known to have a high density of muscarinic receptors. Our study demonstrates that phMRI of mAChR stimulation in rats allows functional assessment of the cholinergic system in vivo. (C) 2010 Elsevier Ltd. All rights reserved.”
“Clade B of the New World arenaviruses contains both pathogenic and

nonpathogenic members, whose surface glycoproteins (GPs) are characterized by different abilities to use the human transferrin receptor type 1 (hTfR1) protein as a receptor. Using closely related pairs of pathogenic and nonpathogenic viruses, we investigated the determinants of the GP1 subunit that confer these different characteristics. We identified a central region (residues 85 to 221) in the Guanarito virus GP1 that was sufficient to interact with hTfR1, with residues 159 to 221 being essential. The recently solved structure of part of the Machupo virus GP1 suggests an explanation for these requirements.”
“Inhibition of pro-survival Bcl-2 family proteins by BH3-only proteins is a key initial step leading to apoptotic cell death. In neurons, investigating cell death pathways is often hampered by the multifactorial nature of the stress stimuli employed. Here we investigate the action of ABT-737, a small molecule inhibitor which specifically targets the BH3-protein binding domain of pro-survival Bcl-2, Bcl-X-L, and Bcl-w.

These results demonstrate that, in these cultured cells, the NR s

These results demonstrate that, in these cultured cells, the NR spontaneous current is almost entirely due by NR2B-containing receptors and that Ni2+ affects the electrical activity through a specific effect on NR channels. (C) 2011 IBRO. Published by Elsevier Ltd. All rights

“We present the case of a patient with retrievable inferior vena cava (IVC) filter-related pseudoaneurysms of the infrarenal aorta and right renal artery, with associated erosion into the duodenal wall. The patient was seen 10 months following multiorgan trauma and placement of a prophylactic retrievable IVC filter (R-IVCF). Management required autogenous aortic reconstruction, caval repair, and subsequent right nephrectomy. This case demonstrates that R-IVCFs may be associated with significant risks, which is concerning, as a majority of prophylactic R-IVCFs placed after multisystem trauma TPCA-1 manufacturer are not removed. (J Vasc Surg 2010;52:1041-4.)”
“Neonatal maternal separation alters adult learning and memory. Previously, we showed that neonatal separation impaired eyeblink conditioning

in adult MK-1775 datasheet rats and increased glucocorticoid receptor (GR) expression in the cerebellar interpositus nucleus, a critical site of learning-related plasticity. Daily neonatal separation (1 h/day on postnatal days 2-14) increases neonatal plasma corticosterone levels. Therefore, effects of separation on GR expression in the interpositus and consequently adult eyeblink conditioning may be mediated by neonatal increases in corticosterone. As a first step in exploring a potential VEGFR inhibitor role for corticosterone in the neonatal separation effects we observed, we assessed whether systemic daily (postnatal days 2-14) corticosterone

injections mimic neonatal separation effects on adult eyeblink conditioning and GR expression in the interpositus. Control uninjected animals were compared to animals receiving either daily corticosterone injections or daily injections of an equal volume of vehicle. Plasma corticosterone values were measured in a separate group of control, neonatally separated, vehicle injected, or corticosterone injected pups. In adulthood, rats underwent surgery for implantation of recording and stimulating electrodes. After recovery from surgery, rats underwent 10 daily sessions of eyeblink conditioning. Then, brains were processed for GR immunohistochemistry and GR expression in the interpositus nucleus was assessed. Vehicle and corticosterone injections both produced much larger increases in neonatal plasma corticosterone than did daily maternal separation, with the largest increases occurring in the corticosterone-injected group. Neonatal corticosterone injections impaired adult eyeblink conditioning and decreased GR expression in the interpositus nucleus, while the effects of vehicle injections were intermediate.

Subanalysis was done for stricture etiology by patient age and st

Subanalysis was done for stricture etiology by patient age and stricture site.

Results: The most important causes were idiopathy, transurethral resection, urethral catheterization, pelvic fracture and hypospadias surgery. Overall iatrogenic causes (transurethral resection, urethral catheterization, cystoscopy, prostatectomy, brachytherapy and hypospadias surgery) were the etiology in 45.5% of stricture cases. In patients younger than 45 years the main causes were idiopathy, hypospadias surgery and pelvic fracture. In patients older than 45 years the main causes were transurethral resection and idiopathy.

In cases of penile urethra hypospadias surgery idiopathic stricture, urethral catheterization and lichen sclerosus were the main causes, selleck chemicals while in the bulbar urethra idiopathic BAY 63-2521 mouse strictures were most prevalent, followed by strictures due to transurethral resection. The main cause of multifocal/panurethral anterior stricture disease was urethral catheterization, while

pelvic fracture was the main cause of posterior urethral strictures.

Conclusions: Of strictures treated with urethroplasty today iatrogenic causes account for about half of the urethral stricture cases in the developed world. In about I of 3 cases no obvious cause could be identified. The etiology is significantly different in younger vs older patients and among stricture sites.”
“Several studies have reported that brain-derived neurotrophic factor (BDNF) might be associated with nicotine dependence. However, there are few click here studies on BDNF levels in humans with nicotine dependence. In the present study, we compared the differences in plasma BDNF levels in patients with nicotine dependence and in healthy nonsmokers, and we investigated serial changes in plasma BDNF levels in patients with nicotine dependence following smoking cessation. Forty-five voluntary smokers and 66 nonsmokers were recruited in this study. Of the 45

smokers, 12 were taking varenicline, 21 were using a nicotine patch, and 12 were unaided in their cessation effort by their own choice. Plasma BDNF levels were measured at baseline using an enzyme-linked immunosorbent assay (both smokers and nonsmokers) and at weeks 4 and 12 after smoking cessation (abstinent smokers only). A total of 19 smokers were able to remain abstinent during the entire study period. Baseline plasma BDNF levels were significantly lower in smokers compared to nonsmokers (F = 4.410, p = 0.002). The plasma BDNF levels in the abstinent smokers significantly increased from baseline after 4 weeks of smoking cessation (z = -2.86, p = 0.004) but had a tendency of decrease in the period between weeks 4 and 12. We could not find differences in the plasma BDNF levels among the three smoker subgroups at week 12 following cessation. Changes in plasma BDNF levels might be related to the process of abstinence and the pathophysiology of nicotine dependence. (C) 2009 Elsevier Ireland Ltd.

A fluorescent dye uptake approach in cultured smooth muscle

A fluorescent dye uptake approach in cultured smooth muscle PD0332991 nmr cells was used to determine whether these cells have functional hemichannels. Results: We report for the first time that pannexins are expressed in the cerebral vasculature. We reveal that pannexin 1 is expressed in smooth muscle but not in endothelium and pannexin 2 is expressed in both endothelium and

smooth muscle. Fluorescent dye entered cultured smooth muscle cells in the absence of extracellular calcium or when the cells were depolarized, which was prevented by the putative hemichannel blocker carbenoxolone. Conclusions: The identification of pannexins in rat MCA indicates that pannexin expression is not restricted to neuronal cells. Dye uptake in cultured smooth muscle cells exhibited properties similar to those of connexin and pannexin hemichannels, which may represent another form of cell-to-cell communication within the vasculature. Copyright (C) 2012 S. Karger AG, Basel”
“Antagonists that are sufficiently selective to preferentially block GluN2A-containing N-methyl-D-aspartate receptors (NMDARs) over GluN2B-containing BAY 11-7082 in vitro NMDARs are few in number. In this study we describe a pharmacological characterization of 3-chloro-4-fluoro-N-[4-[[2-(phenylcarbonyl)hydrazino]carbonyl] benzyl]benzenesulphonamide (TCN 201), a sulphonamide derivative, that

was recently identified from a high-throughput screen as a potential GluN2A-selective selleck inhibitor antagonist. Using two-electrode

voltage-clamp (TEVC) recordings of NMDAR currents from Xenopus laevis oocytes expressing either GluN1/GluN2A or GluN1/GluN2B NMDARs we demonstrate the selective antagonism by TCN 201 of GluN2A-containing NMDARs. The degree of inhibition produced by TCN 201 is dependent on the concentration of the GluN1-site co-agonist, glycine (or D-serine), and is independent of the glutamate concentration. This GluN1 agonist-dependency is similar to that observed for a related GluN2A-selective antagonist, N-(cyclohexylmethyl)-2[5-[(phenylmethyl)amino]-1,3,4-thiadiazol-2-ylthio]acetamide (TCN 213). Schild analysis of TCN 201 antagonism indicates that it acts in a non-competitive manner but its equilibrium constant at GluN1/GluN2A NMDARs indicates TCN 201 is around 30-times more potent than TCN 213. In cortical neurones TCN 201 shows only modest antagonism of NMDAR-mediated currents recorded from young (DIV 9-10) neurones where GluN2B expression predominates. In older cultures (DIV 15-18) or in cultures where GluN2A subunits have been over-expressed TCN 201 gives a strong block that is negatively correlated with the degree of block produced by the GluN2B-selective antagonist, ifenprodil. Nevertheless, while TCN 201 is a potent antagonist it must be borne in mind that its ability to block GluN2A-containing NMDARs is dependent on the GluN1-agonist concentration and is limited by its low solubility.

The anxiogenic drug yohimbine, which causes stress-like responses

The anxiogenic drug yohimbine, which causes stress-like responses in humans and non-humans, reliably reinstates alcohol and food seeking in a rat relapse model.

Yohimibine is a prototypical alpha-2 adrenoceptor antagonist, but results from studies on noradrenaline’s role in yohimbine-induced reinstatement of drug and food seeking are inconclusive. Here, we further addressed this issue by studying the effect of the alpha-1 adrenoceptor antagonist prazosin and the alpha-2 adrenoceptor agonist guanfacine on yohimbine-induced reinstatement.

In click here exp. 1, we trained rats to self-administer alcohol (12% w/v, 1 h/day), and after extinction of alcohol-reinforced lever pressing, we tested prazosin’s (0.5, 1.0, and 2.0 mg/kg, i.p.) or guanfacine’s (0.125, 0.25, and 0.5 mg/kg, i.p.) effect on yohimbine (1.25 mg/kg, i.p.)-induced reinstatement; we also examined prazosin’s effect on intermittent-footshock-stress-induced reinstatement. In exp. 2, we trained food-restricted rats to self-administer 45 mg food pellets and first examined prazosin’s or guanfacine’s effects on food-reinforced responding, and then, after extinction of lever presses, on yohimbine-induced reinstatement.

Prazosin Tanespimycin chemical structure (0.5-2.0 mg/kg) blocked yohimbine-induced reinstatement

of food and alcohol seeking, as well as footshock-induced reinstatement of alcohol seeking. Guanfacine attenuated yohimbine-induced reinstatement of alcohol seeking at the highest dose (0.5 mg/kg), but its effect on yohimbine-induced reinstatement of food seeking was not significant. Neither prazosin nor guanfacine affected high-rate food-reinforced responding.

Results demonstrate an important role of postsynaptic alpha-1 adrenoceptors in stress-induced reinstatement of alcohol and food seeking.”
“Background Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. We aimed to identify specific variants underlying genetic effects shared between the five selleck products disorders in the Psychiatric

Genomics Consortium: autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia.

Methods We analysed genome-wide single-nucleotide polymorphism (SNP) data for the five disorders in 33 332 cases and 27 888 controls of European ancestory. To characterise allelic effects on each disorder, we applied a multinomial logistic regression procedure with model selection to identify the best-fitting model of relations between genotype and phenotype. We examined cross-disorder effects of genome-wide significant loci previously identified for bipolar disorder and schizophrenia, and used polygenic risk-score analysis to examine such effects from a broader set of common variants. We undertook pathway analyses to establish the biological associations underlying genetic overlap for the five disorders.