Morphine activation of mu opioid receptors causes disinhibition of neurons in the ventral tegmental area mediated by β-arrestin2 and c-Src

Abstract The tyrosine kinase, c-Src, participates in mu opioid receptor (MOP) mediated inhibition in sensory neurons in which β-arrestin2 (β-arr2) is implicated in its recruitment. Mice lacking β-arr2 exhibit increased sensitivity to morphine reinforcement; however, whether β-arr2 and/or c-Src participate in the actions of opioids in neurons within the reward pathway is unknown. It is also unclear whether morphine acts exclusively through MOPs, or involves delta opioid receptors (DOPs). We examined the involvement of MOPs, DOPs, β-arr2 and c-Src in the inhibition by morphine of GABAergic inhibitory postsynaptic currents (IPSCs) recorded from neurons in the mouse ventral tegmental area. Morphine inhibited spontaneous IPSC frequency, mainly through MOPs, with only a negligible effect remaining in MOP−/− neurons. However, a reduction in the inhibition by morphine for DOP−/− c.f. WT neurons and a DPDPE-induced decrease of IPSC frequency revealed a role for DOPs. The application of the c-Src inhibitor, PP2, to WT neurons also reduced inhibition by morphine, while the inactive PP3, and the MEK inhibitor, SL327, had no effect. Inhibition of IPSC frequency by morphine was also reduced in β-arr2−/− neurons in which PP2 caused no further reduction. These data suggest that inhibition of IPSCs by morphine involves a β-arr2/c-Src mediated mechanism

Measurement of the B0 anti-B0 oscillation frequency using l- D*+ pairs and lepton flavor tags

The oscillation frequency Delta-md of B0 anti-B0 mixing is measured using the partially reconstructed semileptonic decay anti-B0 -> l- nubar D*+ X. The data sample was collected with the CDF detector at the Fermilab Tevatron collider during 1992 - 1995 by triggering on the existence of two lepton candidates in an event, and corresponds to about 110 pb-1 of pbar p collisions at sqrt(s) = 1.8 TeV. We estimate the proper decay time of the anti-B0 meson from the measured decay length and reconstructed momentum of the l- D*+ system. The charge of the lepton in the final state identifies the flavor of the anti-B0 meson at its decay. The second lepton in the event is used to infer the flavor of the anti-B0 meson at production. We measure the oscillation frequency to be Delta-md = 0.516 +/- 0.099 +0.029 -0.035 ps-1, where the first uncertainty is statistical and the second is systematic.Comment: 30 pages, 7 figures. Submitted to Physical Review

Massage-like stroking boosts the immune system in mice

Recent clinical evidence suggests that the therapeutic effect of massage involves the immune system and that this can be exploited as an adjunct therapy together with standard drug-based approaches. In this study, we investigated the mechanisms behind these effects exploring the immunomodulatory function of stroking as a surrogate of massage-like therapy in mice. C57/BL6 mice were stroked daily for 8 days either with a soft brush or directly with a gloved hand and then analysed for differences in their immune repertoire compared to control non-stroked mice. Our results show that hand-but not brush-stroked mice demonstrated a significant increase in thymic and splenic T cell number (p lt 0.05; p lt 0.01). These effects were not associated with significant changes in CD4/CD8 lineage commitment or activation profile. The boosting effects on T cell repertoire of massage-like therapy were associated with a decreased noradrenergic innervation of lymphoid organs and counteracted the immunosuppressive effect of hydrocortisone in vivo. Together our results in mice support the hypothesis that massage-like therapies might be of therapeutic value in the treatment of immunodeficiencies and related disorders and suggest a reduction of the inhibitory noradrenergic tone in lymphoid organs as one of the possible explanations for their immunomodulatory function

Nutritive value of unconventional fibrous ingredients fed to Guinea pigs in the Democratic Republic of Congo

peer reviewedThe energy and protein value for Guinea pigs (GP) of 9 forages (7 dicots and 2 grasses) and 5 hay-based diets was determined. The apparent faecal digestibility of dry matter, organic matter, crude protein and energy was measured on GP housed in metabolic cages. The forages and the diets were digested in vitro using pepsin and pancreatin hydrolysis and gas fermentation test to simulate stomach, small intestine and large intestine, respectively. Most of the dicots had high digestible crude protein content (152–201 g/kg DM) and the 2 grasses showed lower values (80–85 g/kg DM). Digestible energy content of the forages ranged between 5.79 to 13.08 MJ/kg DM. None of the forage species or hay-based diets provided sufficient energy to supply the 11.7 MJ/kg metabolic energy requirements. The influence of intestinal fermentation on energy and protein values was highlighted by correlations (P<0.05) between in vivo and in vitro data, including gas fermentation. It is the first time that such relationships are reported in single-stomach animals

Association between perinatal depression in mothers and the risk of childhood infections in offspring: a population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Previous studies have suggested that children of mothers who experience depression during the perinatal period may have more infections, but such studies are few in number and none have been carried out in the United Kingdom (UK) population. The aim of this study was to investigate the association between perinatal depression in mothers and the risk of childhood infections in offspring in the UK general population.</p> <p>Methods</p> <p>We used data from The Health Improvement Network (THIN), a large database of electronic primary care medical records to conduct a cohort study among all first-born singleton children born and enrolled in THIN between 1988 and 2004. We used Poisson regression to compare the incidence of gastrointestinal infections and lower respiratory tract infections reported between birth and age 4 years among children of mothers with a record of perinatal depression with those born to mothers with no such history.</p> <p>Results</p> <p>Children of mothers with perinatal depression had a 40% increased risk of gastrointestinal infections and a 27% increased risk of lower respiratory tract infections compared with children of mothers without perinatal depression (incidence rate ratios = 1.40 and 1.27; 95% confidence intervals 1.37-1.42 and 1.22-1.32, respectively). On restricting to antibiotic-treated infections there was a slight increase in the magnitude of association with gastrointestinal infections but a decrease in that with lower respiratory tract infections (incidence rate ratios = 1.47 and 1.19; 95% confidence intervals 1.34-1.61 and 1.11-1.27, respectively).</p> <p>Conclusions</p> <p>Maternal perinatal depression is associated with increased rates of childhood gastrointestinal infections, particularly more severe infections, and lower respiratory tract infections in the UK. Preventing maternal perinatal depression may avoid substantial morbidity among offspring, although further work is also needed to investigate the detailed reasons for these findings.</p

Pregnant women become insensitive to cold stress

BACKGROUND: The function of the hypothalamic-pituitary-adrenal (HPA) axis is known to be altered during pregnancy, but it has not been tested with a natural stressor. METHODS: A group of pregnant women (n = 10) were tested towards the end of pregnancy (mean 36.8 ± 2.5 weeks gestation) and about 8 weeks postpartum (mean 7.8 ± 1.5 weeks), together with a matched control group, with a one minute cold hand stressor test. Saliva samples were collected before and 10 and 20 minutes after the test, and stored for later radioimmunoassay of cortisol. RESULTS: The control group showed a highly significant response to the test. The pregnant group showed no response, and the postpartum group a variable but non significant one CONCLUSIONS: This shows that the HPA axis becomes hypofunctional to a natural stressor at the end of pregnancy. It is suggested that one possible evolutionary function for this is to protect the fetus from the stress responses of the mother

Search for Neutral Supersymmetric Higgs Bosons in ppˉp\bar{p} Collisions at s=1.8\sqrt{s}=1.8 TeV

We present the results of a search for neutral Higgs bosons produced in association with $b$ quarks in $p\bar{p}\to b\bar{b} \phi\to b\bar{b}b\bar{b}$ final states with $91 \pm 7$ pb$^{-1}$ of $p\bar{p}$ collisions at $\sqrt{s}=1.8$ TeV recorded by the Collider Detector at Fermilab. We find no evidence of such a signal and the data is interpreted in the context of the neutral Higgs sector of the Minimal Supersymmetric extension of the Standard Model. With basic parameter choices for the supersymmetric scale and the stop quark mixing, we derive 95% C.L. lower mass limits for neutral Higgs bosons for \tb values in excess of 35.Comment: 2 tex files 3 figure

Measurement of the Top Quark p T Distribution

We have measured the p(T) distribution of top quarks that are pair produced in p (p) over bar collisions at roots = 1.8 TeV using a sample of t (t) over bar decays in which we observe a single high-P-T charged lepton, a neutrino, and four or more jets. We use a likelihood technique that corrects for the experimental bias introduced due to event reconstruction and detector resolution effects. The observed distribution is consistent with the standard model prediction. We use these data to place limits on the production of high-p(T) top quarks suggested in some models of anomalous top quark pair production