A summary of some of the practical difficulties that arise in using NSP ELISA to help substantiate FMD freedom is provided in Supplementary Table 4. Three inhibitors workshops in 2007 examined the design and interpretation of post FMD-vaccination serosurveillance by NSP tests [52]. Their aim was to test the feasibility and consequences of applying the above-described rules after applying emergency

vaccination in three plausible scenarios involving different outbreak sizes, affected species and livestock densities. The summary recommendations of the workshops are provided in Supplementary Table 5 and the following key issues are further discussed below: (1) the requirement to sample all vaccinated selleck chemicals animals; (2) the follow-up investigation required to establish the significance of seroreactors identified;

(3) the criteria for removal of seropositive animals and herds; (4) what can be done with such animals (slaughter for consumption or destruction); (5) the impact of finding seroreactors during the process of surveillance with the Akt inhibitor objective of regaining the status “FMD free where vaccination is not practised”. Even with tests of suboptimal sensitivity (70–90%), a low prevalence of infection can be detected with high confidence in large groups of animals without sampling and testing every animal. However, in large herds, the animals are often segregated in smaller groups that may be considered as separate epidemiological

units and in this case, the number of animals per epidemiological unit would be the denominator for calculation of sample sizes. For NSP serosurveillance, using a test with Sp = 0.995 and Se = 0.7, then detection of seroconversion at 95% confidence, at a prevalence of 2%, in an epidemiological unit of 1000 animals, would require 513 animals to be sampled and the cut-point would be five (i.e. finding five or fewer reactors could still be consistent with absence of true seroconversion, i.e. probability of 2% or more seropositive animals is less than 5%). If it were accepted that only strongly seroconverting animals are likely to (have) spread infection, then the Se figure could be increased to 0.9, in which case 366 samples would need to be tested and the cut-point would become four (FreeCalc; [53]). Reduction L-NAME HCl of the numbers sampled in large herds is often relevant for pigs which also do not have risks associated with the development of FMDV carriers. Clinical disease is also rather obvious in pigs so that NSP surveys add less value. Therefore, surveillance in pigs should be targeted towards the identification of disease and virus circulation. Studies on vaccinated pig herds in Hong Kong suggested an all-or-nothing effect, with widespread clinical disease and NSP seroconversion (49–82% seroprevalence) or neither clinical disease nor seroconversion [54].

A p-value <0.05 was considered as statistically significant. All statistical analysis was performed by SAS software version 9.1.3 (SAS Institute, Cary, NC, USA). For planning the study, we assumed that approximately 20% of enrolled AGE cases might get detected as RV positive and it was based on earlier outpatient setting studies in India [15] and [16]. With this expected proportion of rotavirus positivity, 500 was the targeted (PP) population for enrolling AGE subjects. It was planned that each Libraries region would provide complete data of at least 100

subjects. We initiated the study at a total of 10 sites with two sites located in each geographical region (i.e., north, south, east, west, and center) of India. These sites started enrolling subjects from December 2011. Due to inadequate enrollment from one site and region as a whole, in northern region, we initiated enrollment at an additional site Selleck LEE011 in July 2012, taking GSK126 the total number of sites to 11. Enrollment at the new site and existing site in the region was competitive. We screened a total of 616 children for eligibility for participation in this study (Fig. 1). We found 98.2% (605/616) eligible subjects and enrolled them

in the study. The study collected stool samples from all subjects (n = 605). Site staff contacted the parent/guardian of all subjects (n = 605) by telephone for data collection after Day 7 and Day 14, for collecting information for Non-specific serine/threonine protein kinase Day 1–Day 7 and Day 8–Day 14, respectively. Out of 552 subjects in PP population, three sites in

north India had 109 (16 + 59 + 34) subjects; two sites each in south, east, west, and center of India had 99 (47 + 52), 113 (55 + 58), 111 (58 + 53), 120 (45 + 75) subjects, respectively. From majority of the subjects (89.7% [495/552]) stool samples were collected within 2 days of enrollment. EIA testing was possible for samples of 91.2% (552/605) subjects’ stool samples. EIA testing could not be performed for stool samples of 8.8% (53/605) subjects for reasons such as insufficient quantity of samples (n = 46), samples not labeled (n = 4), and inappropriate enrollment (disease symptoms occurred >3 days prior to enrollment as opposed to protocol requirement) (n = 3). In addition to laboratory results (for EIA), complete per protocol data was available for these 552 subjects and they formed the PP population. The demographic characteristics are presented in Table 1. Mean (±SD) age of subjects was 17.0 (±12.6) months. RV positive subjects were younger compared to RV negative subjects (mean age ± SD was 14.8 ± 10.1 months vs. 17.6 ± 13.2 months); this difference was not statistically significant. The distribution of cases by age revealed statistically significant (p = 0.0081) proportion of RV positive cases in ≤24 months age group.

, 2012). The findings

presented above may reassure parents and providers who are reluctant to vaccinate due to concerns about risk compensation. However, as noted by Stupiansky and Zimet (2013), “… it is important to remember that risk compensation (real or imagined) is see more not a rationale for withholding vaccine. Instead, it is a rationale for ensuring adequate education both pre- and post-vaccination” (p. 262). Underlying some parental HPV Modulators vaccine concerns (e.g., feeling that HPV vaccine is too new) are questions about vaccine safety (Fisher, 2012; Krawczyk et al., unpublished results). Fear-inducing news stories may have contributed to these concerns as they sometimes have misreported Vaccine Adverse Event Reporting System data, incorrectly suggesting that HPV vaccination has often led to severe adverse health effects, including death (see, for example the August, 2007 edition of Maclean’s magazine in Canada; Gulli, 2007). Numerous large-scale studies on HPV vaccine safety have been published and show little or no evidence of severe side-effects associated with vaccination

(Agorastos et al., 2009, Chao et al., 2012, Gee et al., 2011, Klein et al., 2012 and Lu et al., 2011). www.selleckchem.com/products/PLX-4032.html The most frequently reported side-effects are similar to those reported with other vaccines and are transient events, such as mild pain and bruising at the injection site, faintness, and syncope (Naleway et al., 2012). It is important to highlight that a reported adverse event after vaccination does not automatically mean that it was caused by the vaccine. A major challenge, however, is how to effectively communicate to parents the evidence that HPV vaccine is quite safe. As noted following, an additional challenge involves communicating 17-DMAG (Alvespimycin) HCl the very substantial risks of non-vaccination, in the context of generalized, relatively early, sexual debut, delayed marriage, serial monogamy, and the accumulation of risk of HPV infection over

time. Development of effective strategies for clearly and accurately communicating information about risk of vaccines has been an enduring focus of vaccine researchers (Ball et al., 1998, Betsch and Sachse, 2013, Davis et al., 2001 and Offit and Coffin, 2003). Best practices in this regard may rest on the nature of the vaccine (routine versus elective), the controversies that may surround the vaccine (e.g., MMR and autism, HPV and risk compensation), and, importantly, whether parents or patients harbor ongoing concerns about HPV vaccine safety, actively ask about vaccine safety, or have no concerns in this area. Suggestions for communication about HPV vaccine safety include asking patients whether they have any questions about the vaccine and providing accurate information (including credible websites) that can address concerns about safety.

We conclude that opportunities are being missed to identify children with incomplete vaccination; and that strategies to enhance vaccination coverage should pay special attention to the needs of families living in inadequate housing; and that surveillance and health promotion actions in primary health facilities

and DCCs should be improved Tyrosine Kinase Inhibitor Library molecular weight performed as concomitant activities [19]. Finally, given the relevance of parental–childhood characteristics, we recommend that qualitative studies approaching the parental perception of the need and security to have their children inoculated with vaccine and cultural dimension aspects should be performed to evidence behavioral characteristics susceptible to health interventions [20]. The present study is integral part of Projeto CrechEficiente, financed by the Fundacão de Amparo à Pesquisa do Estado de São Paulo (FAPESP), process no. 2006/02597-0. The authors thank

the principals of the day-care centres for their assistance in the process of obtaining the informed consent and in data collection. The authors also express their appreciation to Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) for funding the research project. Contributors: Crizotinib T.K. wrote the article, selected the study design, and performed the data analysis and interpretation. L.C.R. contributed to the data analysis and interpretation, and collaborated writing the article. T.K. and J.A.A.C.T. collaborated in the study

conception, participated in the process of selecting the survey instrument and sampling 3-mercaptopyruvate sulfurtransferase strategy, and collaborated in the data collection. All authors approved the contents of the manuscript. Conflict of interest statement: The authors have no conflict of interest. “
“Dengue is a major public health concern throughout tropical and sub-tropical regions of the world. It is the most rapidly spreading mosquito-borne viral disease, with a 30-fold increase in worldwide incidence over the last 50 years [1]. It is estimated that there are more than 50 million dengue infections each year and almost half the world’s population live in countries in which dengue is endemic [1] and [2]. While dengue is a global concern, with a steady increase in the number of countries reporting dengue, currently close to 75% of the global dengue burden is borne by the Asia-Pacific region [1]. Attempts to control dengue are focused on control of the mosquito vector [3]. Integrated vector management programmes have been shown to be effective in reducing total numbers of the vector [4]. However, many vector control programmes have little to no effect on dengue incidence [5] and those that are successful can have difficulties with sustainability [6]. The limitations of vector control include the cost of maintaining control programmes, the difficulty of Libraries destroying all mosquitoes in an area, and the movement of mosquitoes across borders.

16 Negative ESI–MS m/z 609 [M–H]ˉ, m/z 595 [M–H]−m/z 431 [M–H]− of compounds 3, 4 and 7 confirming their structures as rutin, quercetin-3-O-arabinoglucoside and isoquercetin, respectively, together with their aglycone

peak of quercetin at m/z 301 [quercetin-H]−, which is also of compound 10. 17 Compound 6 was obtained as yellow amorphous powder (18 mg), chromatographic properties: Rf values; 0.38 (S1), 0.44 (S2); dark purple spot under UV-light, turned to yellow fluorescence on exposure to ammonia vapors. It gave deep green color and orange fluorescence with FeCl3 and Naturstoff spray reagents, respectively. It showed λmax (nm) (MeOH): 257, 356; (+NaOMe): 272, 326 (sh), 404; (+NaOAC): 273, 323 (sh), 373; (+AlCl3): 275, 433; (+AlCl3/HCl): 270, 360 (sh), 404. Complete acid hydrolysis learn more resulted in l-arabinose in aqueous phase and quercetin in organic phase (CoPC). 1H NMR (300 MHz, DMSO-d6): δ ppm 12.54 (1H, s, H-bonded OH-5), 7.50 (1H, dd, J = 8.4, 2.5 Hz, H-6′), 7.48 (1H,

d, J = 2.5 Hz, H-2′), 6.82 (1H, d, J = 8.4 Hz, H-5′), 6.38 (1H, d, J = 2.4 Hz, H-8), 6.16 (1H, d, J = 2.4 Hz, H-6), 5.50 (1H, d, J = 1.3 Hz, H-1″), 4.11 (1H, br s, H-2″). 13C NMR (75 MHz, DMSO-d6): δ ppm 178.11 (C-4), 164.77 (C-7), 161.63 (C-5), 156.88 (C-2/9), 148.95 (C-4′), 145.52 (C-3′), 133.84 (C-3), 122.23 (C-6′), 121.44 (C-1′), 116.10 SCR7 nmr (C-5′/2′), 108.34 (C-1″), 104.42 (C-10), 99.26 (C-6), 94.20 (C-8), 86.32 (C-4″), 82.55 (C-2″), much 77.43 (C-3″), 61.13 (C-5″). On the basis of its chromatographic properties and UV-spectral data, as the previous explained compounds, compound 6 was expected to be quercetin 3-O-glycoside. The acid hydrolysis of 6 afforded quercetin as an aglycone and the sugar moiety was identified as arabinose by CoPC. Negative ESI-MS spectrum exhibited a molecular ion peak at m/z 433.56 [M–H]−, corresponding to molecular weight 434 and molecular formula C20H18O11 for quercetin pentoside, this was further supported

by the fragment ions at m/z 867.12 [2M–H]−, for the dimeric adduct ion and at 301.30 [quercetin-H]−, for quercetin aglycone. 1H NMR spectrum showed a douplet at δ ppm 5.50 with J = 1.3 Hz was characteristic for the anomeric proton of α-l-arabinofuranoside moiety. 1813C NMR spectrum showed in addition to 15 carbon resonances for 3-O-glycosyl-quercetin, 18 three highly downfield shifted peaks at 108.34, 86.32, 82.55 assignable to C-1″, C-4″, and C-2″ of an arabinofuranoside moiety by inhibitors compared to data. 17, 19 and 20 Accordingly compound 6 was identified as Quercetin 3-O-α-L-arabinofuranoside, which was isolated before from R. polystachya 3 but first time from this species. Compounds 5 and 9 showed UV spectra of two major absorption bands in methanol at λmax 268 nm (band II) and at λmax 333 nm (band I) indicating its flavonoid nature giving the chromatographic properties of the characteristic apigenin nucleus.

For example, the Tmax of levofloxacin was prolonged by 50% following efavirenz concurrent administration and this was ascribed to up-regulation of P-glycoprotein induced by efavirenz.17 Moreover, in our previous study, the Tmax of proguanil was prolonged significantly following efavirenz concurrent administration and this was ascribed to up-regulation

of P-glycoprotein induced by efavirenz.8 The total systemic exposure (AUCT) of amodiaquine was substantially increased (mean of about 80%) in the presence of efavirenz (Table 1) and, this is quite evident in the Modulators significant difference in the plasma concentration profiles of amodiaquine see more with or without efavirenz (Fig. 1A). The increased systemic drug exposure coupled with the markedly diminished oral drug clearance (Cl/F) and significantly prolonged elimination T1/2

of amodiaquine suggests a systemic inhibition of metabolism of the drug by efavirenz. This assertion is buttressed by the observation of an evident marked reduction MK-1775 supplier in plasma levels of the major metabolite (desethylamodiaquine) (Fig. 1B), which is reflected in significant decreases in the Cmax and AUC of the metabolite. Previous studies have shown that both CYP2C8 and CYP3A4 contribute to the metabolism of amodiaquine but the former is the major contributor in the biotransformation.2 and 16 Since efavirenz has been demonstrated as an inhibitor of CYP2C8 as well as a mixed inducer/inhibitor of CYP3A4,9 the increase in plasma levels of amodiaquine following co-administration with efavirenz is most likely due to the inhibition of CYP2C8 and probably a contribution from CYP3A4 inhibition. In a study,18 looking at amodiaquine pharmacokinetics of following co-administration of efavirenz (600 mg once daily) and amodiaquine/artesunate (600/250 mg once daily) in HIV-subjects had to be terminated after the first two subjects developed

asymptomatic but significant elevations of liver transaminases. Addition of efavirenz increased amodiaquine AUC by 114% and 302% in the 1st and 2nd subjects respectively. Table 1 shows a pronounced decrease (68%) in the ratio of AUC of second metabolite to that of unchanged drug, the metabolic ratio (MR). This further strengthens the point that a metabolic interaction occurs between amodiaquine and efavirenz, and that efavirenz inhibits the metabolism of amodiaquine. The increased plasma levels of amodiaquine with efavirenz co-administration may increase the toxicity of amodiaquine. After oral administration, amodiaquine is rapidly absorbed from the gastrointestinal tract. In the liver it undergoes rapid and extensive metabolism to N-desethyl-amodiaquine (DEAQ) which concentrates in blood cells. 2 Amodiaquine is three-times more potent than DEAQ but the concentration of amodiaquine in blood is quite low.

22, 23 and 24The present work aims to study the application of conductometric method in the quality control of loperamide hydrochloride and trimebutine. The present work deals with the investigation

Paclitaxel ic50 of a simple, rapid and accurate method for the determination of LOP.HCl and TB, as raw materials and in some pharmaceutical preparations with no interference of other constituents in their formulations. The conductometric measurements were carried out with a conductivity meter model (702) Conda. The measurements range was 1.0–20.0 microsimens with a Libraries maximum error of ±0.2%. A dip type conductivity cell (K = 1.00) was used. Loperamide hydrochloride (LOP.HCl, M.W. = 513.5 g mol−1) and its pharmaceutical preparation (Imodiumcapsules labeled to contain 2 mg LOPHCl/capsule) was provided from Alexendria for Pharmaceutical Industries, Egypt. Trimebutine (TB, M.W. = 387.48 g mol−1) and its pharmaceutical preparation (Triton tablets labeled to contain 100 mg trimebutine/tablet) were provided from Amoun Pharma, Egypt. Phosphotungestic selleck chemicals llc acid (PTA) H3 [PW12O40 × H2O] was obtained from Aldrich Chemical Company.

Aqueous solutions of PTA was prepared by dissolving the accurately weighed amounts of the pure solid in bi-distilled water using analytical grade purity chemicals, and the exact concentrations of these solutions were determined by Thiamine-diphosphate kinase the appropriate recommended methods.25 and 26 Solutions were kept in the refrigerator for not more than 1 week. Working solutions were freshly prepared

by appropriate dilution. Aliquots of working solutions containing 5.13–42.59 mg of LOP.HCl and 3.87–38.75 mg of TB were transferred to 75 mL volumetric flask and made up to the mark with bi-distilled water. The contents of the volumetric flask were transferred to the titration cell, then 1.0 × 10−2 mol L−1 PTA, was added using a micro-burette, and the conductance was measured after 1–2 min after each addition of reagent through stirring. The conductance reading was corrected for dilution27 by means of the following equation, assuming that conductivity is a linear function of dilution: Ωcorr = Ωobs [(V1 + V2)/V1]where Ωcorr and Ωobs are the corrected and the observed electrolytic conductivities, respectively, V1 is the initial volume and V2 is the volume of the added reagent. A graph of corrected conductivity values versus the volume of the added titrant was constructed and the end point was determined. The drug–titrant ratio is then determined from the intercept of the two linear segments of the graph. A suitable aliquots (1.0–10.0) mL of 10−2 mol L−1 LOP.HCl and TB were transferred into a 75 mL volumetric flask and diluted up to the mark with bi-distilled water.

This feature makes it particularly attractive in accounting for the effects of strabismus, where two pathways can be equally active but are not correlated. It is not yet clear

what signaling mechanisms would dissociate STDP from LTD/LTP or other forms of plasticity. Calcium influx through CP-690550 manufacturer NMDARs (Daw et al., 1993) triggers downstream effectors including protein kinases and phosphatases that are hypothesized to regulate ODP by controlling phosphorylation of substrates thought to be important for synaptic transmission, neuronal excitability, and morphological stabilization: RII-α and RII-β isoforms of cAMP-dependent protein kinase (PKA) (Fischer et al., 2004 and Rao et al., 2004), extracellular-signal-regulated kinase (ERK) (Di Cristo et al., 2001), α-calcium/calmodulin-dependent

PI3K Inhibitor Library datasheet protein kinase II (αCaMKII) (Taha et al., 2002), and the phosphatase calcineurin (Yang et al., 2005). In all cases, preventing the activation of the kinases or promoting the activation of the phosphatase prevented the reduction in deprived-eye responses. Collectively, these studies suggest that the balance between protein kinases and phosphatases is important for critical period ODP. The activity-dependent immediate early gene Arc is a potential mediator of protein synthesis-dependent plasticity. Arc gene expression and efficient Arc translation are dependent on NMDAR and group 1 metabotropic glutamate receptor (mGluR) activation (Steward and Worley, 2001). In Arc-knockout mice, 3 days of MD failed to reduce deprived-eye responses (McCurry et al., 2010). Another activity-dependent

immediate early gene, serine protease tissue plasminogen activator (tPA), increases during MD in V1 and targets many downstream effectors including extracellular-matrix proteins, growth factors, membrane receptors, and cell-adhesion molecules (Mataga et al., 2002 and references from therein). In tPA-knockout mice critical period ODP was impaired and could be rescued by exogenous tPA (Mataga et al., 2002). MicroRNAs induced by visual experience may also play a role in ODP. Increasing (Tognini et al., 2011) or decreasing (Mellios et al., 2011) the levels of a microRNA enriched in the brain (miR132), reduced critical period ODP and had dramatic effects on spine morphology. It is not yet clear to what extent the changes in visual responses in vivo during ODP are the product of changes in the anatomical circuits, such as loss of synapses serving the deprived eye, or changes in synaptic efficacy, such as LTD, within stable anatomical circuits. Figure 6 illustrates this distinction for the first phase of ODP.

More importantly, pyramidal neurons in Selleckchem HDAC inhibitor the intact brain are constantly bombarded by synaptic input, so much so that they are chronically depolarized and shunted ( Bernander et al., 1991; Destexhe and Paré, 1999; for review see Destexhe et al., 2003). Moreover, sensory input causes concomitant (albeit momentarily unbalanced) increases in both excitatory

and inhibitory drive ( Borg-Graham et al., 1998; Haider et al., 2013; Pouille et al., 2009; for review see Isaacson and Scanziani, 2011), which implies further increases in total conductance. The reduction in input resistance (R = 1/g) decreases neuronal sensitivity to constant and slowly fluctuating (low-frequency) inputs, but the concomitant reduction in the membrane time constant (τ = RC) makes neurons relatively more sensitive to rapidly fluctuating (high-frequency) inputs. In addition, large membrane potential fluctuations driven by synaptic bombardment increase sensitivity to coincident inputs ( Rossant et al., 2011). This tendency is enhanced by a nonlinear increase in adaptation that can further reduce sensitivity to slow input and thus enhance selectivity for fast input ( Hong et al., 2012; Prescott

et al., 2006, 2008b). The cumulative effect is that pyramidal neurons receiving realistic conductance-based background and stimulus-evoked inputs in vivo, BVD-523 research buy and which therefore exist in a high-conductance state, behave more like coincidence detectors than is suggested by in vitro testing with artificial current-based stimuli (see also Azouz and Gray,

2000, 2003). To be clear, pyramidal neurons do not switch abruptly from one to the other operating mode but, instead, shift along a continuum (see Figure 2) and can exhibit reasonably strong coincidence detector traits. Requirement 2 is satisfied insofar as principal neurons do receive synchronous input. For one, the cortex receives sensory input via synchronized activation of thalamocortical neurons (Alonso et al., 1996; Bruno and Sakmann, 2006) originating from the coactivation of primary sensory neurons (see below). Pyramidal neurons recorded in vivo exhibit irregular out spiking (see above) driven by large fluctuations in membrane potential that, based on the small depolarization produced by unitary synaptic events, can only be accounted for by some degree of synchrony among presynaptic cells (Destexhe and Paré, 1999; DeWeese and Zador, 2006). Indeed, cross-cell correlations in membrane potential (Lampl et al., 1999; Poulet and Petersen, 2008; Yu and Ferster, 2010) and spiking (Cohen and Kohn, 2011; deCharms and Merzenich, 1996; Jadhav et al., 2009; Smith and Kohn, 2008) have been documented in vivo.

Since dysfunction of glutamatergic transmission is considered the core feature and fundamental pathology of mental disorders (Tsai and Coyle, 2002, Moghaddam, 2003 and Frankle et al., 2003), in this study, we sought to determine whether repeated (subchronic) stress might negatively influence PFC-mediated cognitive processes by disturbing glutamatergic signaling in juvenile animals. To test the

impact of stress on cognitive functions, we measured the recognition memory task, a fundamental explicit memory process requiring judgments of the prior occurrence of stimuli based on the relative familiarity of individual objects, the association of objects and places, or the recency information (Ennaceur and Delacour, 1988, Dix and Aggleton, 1999 and Mitchell and Laiacona, 1998). Lesion studies have shown that the medial prefrontal cortex plays an obligatory Galunisertib purchase role in the temporal order recognition (TOR) memory (Barker et al., 2007) so this behavioral task was used. Young (4-week-old) male rats, who had been exposed to 7 day repeated behavioral stressors, were examined at 24 hr after stressor cessation. The control groups spent much more time exploring the novel (less recent) object in the test trial (familiar recent object: 9.9 s ± Tenofovir datasheet 2.4 s, novel object: 19.9 s ±

2.4 s, n = 7, p < 0.01), whereas the stressed rats (restraint, 2 hr/day, 7 day) lost the preference to the novel object (familiar recent object: 15.2 s ± 2.4 s; novel object: 11.0 s ± 2.8 s, n = 5, p > 0.05). The discrimination ratio (DR), an index of the object recognition memory, showed a significant main effect (Figure 1A, F3,24 = 9.8, p < 0.001, analysis of variance [ANOVA]). Post hoc analysis indicated a profound impairment of TOR memory by repeated stress (DR in control: 36.7% ± 6.6%, n = 7; DR in stressed: −19.6% ± 3.8%, n = 5, p < 0.001), which was blocked by systemic injection of the GR antagonist RU486 (DR in RU486: 41.6% ± 9.0%, n = 6; DR in RU486+stress: mafosfamide 38.8% ± 11.2%, n = 7, p > 0.05). To test whether GR in the PFC mediates the detrimental effect of repeated stress on cognition, we performed stereotaxic injections of RU486, vehicle control, or corticosterone to PFC prelimbic regions

bilaterally via an implanted guide cannula (Yuen et al., 2011). A significant main effect was found (Figure 1B, F4,30 = 5.1, p < 0.005, ANOVA), and post hoc analysis indicated that repeated restraint stress impaired TOR memory in rats injected with vehicle (DR in veh: 38.7% ± 12.0%, n = 7; DR in veh+stress: −17.5% ± 9.1%, n = 6, p < 0.01), an effect mimicked by repeated CORT injections (0.87 nmol/g, 7 day, −10.5% ± 12.7%, n = 6, p < 0.05), whereas such impairment was prevented by RU486 delivered to PFC (1.4 nmol/g, 7 day, DR in RU486: 34.2% ± 17.8%, n = 6; DR in RU486+stress: 36.1% ± 6.1%, n = 6, p > 0.05). It suggests that repeated stress influences cognitive processes via GR activation in the PFC. Next, we examined whether other stressors could produce a similar effect.