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Effective medical treatment of opiate addiction is limited by a high relapse rate in abstinent addicts. Opiate withdrawal causes cAMP superactivation, but the underlying molecular mechanisms are not clear. Recent evidence implicates an activator of G-protein signaling 3 (AGS3) in opiate addiction. We found previously that during a 10-min activation of(More)
There is no effective treatment for cocaine addiction despite extensive knowledge of the neurobiology of drug addiction. Here we show that a selective aldehyde dehydrogenase-2 (ALDH-2) inhibitor, ALDH2i, suppresses cocaine self-administration in rats and prevents cocaine- or cue-induced reinstatement in a rat model of cocaine relapse-like behavior. We also(More)
The nucleus accumbens (NAc) is central to heroin addiction. Activation of opiate receptors in the NAc dissociates G(i/o) into alpha and betagamma subunits. Galpha(i) inhibits cAMP production, but betagamma regulates several molecular pathways, including protein kinase A (PKA). We show in NAc/striatal neurons that opiates paradoxically activate PKA signaling(More)
With increasing adoption and presence of Web services, designing novel approaches for efficient Web services recommendation has become steadily more important. Existing Web services discovery and recommendation approaches focus on either perishing UDDI registries, or keyword-dominant Web service search engines, which possess many limitations such as(More)
Antagonists of adenosine A2A receptors (A2A-antagonists) with different chemical structures have been developed by several pharmaceutical companies for the potential treatment of Parkinson’s disease. Pharmacological characterization of these antagonists was incomplete, and different assay conditions were used in different labs. Therefore, we characterized(More)
Relapse is the most serious limitation of effective medical treatment of opiate addiction. Opiate-related behaviors appear to be modulated by cannabinoid CB1 receptors (CB1) through poorly understood cross-talk mechanisms. Opiate and CB1 receptors are coexpressed in the nucleus accumbens (NAc) and dorsal striatum. These regions also have the highest density(More)
Dopamine release is activated by ethanol and addicting drugs, but molecular mechanisms linking dopaminergic signaling to neuronal responses and drinking behavior are poorly understood. We report that dopamine-D2 receptors induce PKA Calpha translocation and increase CRE-regulated gene expression. Ethanol also activates PKA signaling. Subthreshold(More)
Inhibition of cardiac late sodium current (late I(Na)) is a strategy to suppress arrhythmias and sodium-dependent calcium overload associated with myocardial ischemia and heart failure. Current inhibitors of late I(Na) are unselective and can be proarrhythmic. This study introduces GS967(More)
H ypertrophic cardiomyopathy (HCM) is the most prevalent monogenic cardiac disorder, with a reported prevalence of 1 in 500 worldwide. 1 Despite its epidemiological relevance, HCM is largely an orphan condition because it lacks a disease-specific pharmacological treatment. 2 HCM is the most common cause of arrhythmic sudden cardiac death in young athletes.(More)
Point-of-Interest (POI) recommendation is a new type of recommendation task that comes along with the prevalence of location-based social networks in recent years. Compared with traditional tasks, it focuses more on personalized, context-aware recommendation results to provide better user experience. To address this new challenge, we propose a Collaborative(More)