Rats

were trained to self-administer cocaine (0.23 mg/kg per infusion) for 8-10 days. Subsequently, responding for drug was extinguished, and tests for reinstatement were conducted following: (1) pretreatment with the CRF receptor antagonist, d-Phe CRF(12-41) [1 mu g, intracerebroventricular (i.c.v.)], prior to i.c.v. injections of NA (10 mu g; Experiment 1); (2) pretreatment with the alpha(2) adrenoceptor agonist, clonidine (40 mu g/kg, i.p.), prior to i.c.v. injections of CRF (0.5 mu g; Experiment 2); (3) pretreatment with d-Phe (1, 5 mu g, i.c.v.), prior to systemic injections of the alpha(2) adrenoceptor antagonist, yohimbine (1.25 mg/kg; Experiment 3A); or (4) pretreatment with clonidine (40 mu g/kg, i.p.) prior to systemic injections of yohimbine (0.625 mg/kg, 1.25 mg/kg; Experiment 3B).

NA reliably induced reinstatement, an Tucidinostat in vitro effect that was blocked by pretreatment with d-Phe. In contrast, CRF-induced reinstatement was not attenuated by pretreatment with clonidine. Pretreatment with neither d-Phe nor clonidine was effective RG7112 in blocking yohimbine-induced reinstatement.

Together, the present findings suggest a functional interaction between NA and CRF systems in mediating stress-induced reinstatement of cocaine seeking, whereby

activation of CRF receptors occurs subsequent to, and downstream of, the sites of action of NA.”
“Epstein-Barr virus (EBV) infection

is causatively associated with a variety of human cancers, including nasopharyngeal carcinoma (NPC). The only viral nuclear protein expressed in NPC is EBNA1, DMH1 manufacturer which can alter cellular properties in ways that may promote oncogenesis. Here, we used 2-dimensional difference gel electrophoresis (2-D DiGE) to profile changes in the nuclear proteome that occur after stable expression of EBNA1 in the EBV-negative NPC cell line CNE2. We found that EBNA1 consistently altered the levels of a small percentage of the nuclear proteins. The identification of 19 of these proteins by mass spectrometry revealed that EBNA1 upregulated three proteins affecting metastatic potential (stathmin 1, maspin, and Nm23-H1) and several proteins in the oxidative stress response pathway, including the antioxidants superoxide dismutase 1 (SOD1) and peroxiredoxin 1 (Prx1). Western blot analysis verified that EBNA1 expression upregulated and EBNA1 silencing downregulated these proteins. In addition, transcripts for stathmin 1 were induced by EBNA1, whereas EBNA1 only affected Prx1 and SOD1 at the protein level. Further investigation of the EBNA1 effects on the redox pathway showed that long-term EBNA1 expression in NPC resulted in increased reactive oxygen species (ROS) and increased levels of the NADPH oxidases NOX1 and NOX2, known to generate ROS. In addition, EBNA1 depletion in EBV-positive cells decreased NOX2 and ROS.