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The mammalian target of rapamycin (mTOR) governs cell growth and proliferation by mediating the mitogen- and nutrient-dependent signal transduction that regulates messenger RNA translation. We identified phosphatidic acid (PA) as a critical component of mTOR signaling. In our study, mitogenic stimulation of mammalian cells led to a phospholipase D-dependent(More)
Locomotor activity is a polygenic trait that varies widely among inbred strains of mice (). To characterize the role of D2 dopamine receptors in locomotion, we generated F2 hybrid (129/Sv x C57BL/6) D2 dopamine receptor (D2R)-deficient mice by gene targeting and investigated the contribution of genetic background to open-field activity and rotarod(More)
Genotoxic stress triggers the activation of checkpoints that delay cell-cycle progression to allow for DNA repair. Studies in fission yeast implicate members of the Rad family of checkpoint proteins, which includes Rad17, Rad1, Rad9 and Hus1, as key early-response elements during the activation of both the DNA damage and replication checkpoints. Here we(More)
1. The present study was designed to investigate further the effects of the newly discovered orphanin FQ (OFQ)-the endogenous ligand for the orphan opioid receptor (called, e.g., ORL, and LC132)-on pain modulation in the rat. We used the tail-flick assay as a nociceptive index. 2. When injected into a cerebral ventricle, OFQ (4 fmol-10 nmol) has no effect(More)
Recent studies suggest that the novel opioid peptide orphanin FQ (OFQ) is involved in pain modulation. We found that intracerebroventricular (i.c.v.) administration of OFQ in the rat produced a dose-dependent antagonism of the analgesia induced by 100 Hz electroacupuncture (EA) stimulation as measured in the radiant heat tail-flick assay. Antisense(More)
Low and high frequency electroacupuncture (EA)-produced analgesia have been shown to be mediated by different brain substrates and different opioid peptides. In this study, Fos-like immunoreactivity (FLI) and in situ hybridization of the three opioid mRNAs were used to examine the effect of low (2 Hz) and high (100 Hz) frequency EA on neuronal activities,(More)
Antisense oligodeoxynucleotides (ODNs) of c-fos and/or c-jun were used in this study to investigate the role of Fos and Jun proteins in electroacupuncture (EA)-induced transcription of the opioid genes, preproenkephalin (PPE), preprodynorphin (PPD) and proopiomelanocortin (POMC). As the results showed, EA-induced Fos and fun expression was blocked(More)
There is compelling evidence that endogenous opioid peptides are regulated by exogenous opiates. Our previous studies have shown that the mu-opioid receptor protein and mRNA are down-regulated in the mediobasal hypothalamus of the female guinea pig following chronic morphine treatment. In addition, electrophysiological studies have shown that hypothalamic(More)
1. Our previous work has demonstrated that exogenously administered orphanin FQ (OFQ) antagonizes morphine analgesia and electroacupuncture analgesia (EAA) in the brain and potentiates morphine analgesia and EAA in the spinal cord of the rat. In the present study we evaluated the role of endogenously released OFQ in the development of tolerance to morphine(More)
Recent data suggest that brain-derived neurotrophic factor (BDNF) plays an essential role in neuronal plasticity and etiology of bipolar disorders (BPD). However, results from different studies have been inconsistent. In present study, 342 patients who met DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) criteria for bipolar(More)