Post-traumatic stress disorder (PTSD) is a stress-associated complex and debilitating psychiatric disorder due to an imbalance of neurotransmitters in response to traumatic events or fear. PTSD is characterized by re-experiencing, avoidance behavior, hyperarousal, negative emotions, insomnia, personality changes, and memory problems following exposure to severe trauma. However, the biological mechanisms and symptomatology underlying this disorder are still largely unknown or poorly understood. Considerable evidence shows that PTSD results from a dysfunction in highly conserved brain systems involved in regulating stress, anxiety, fear, and reward circuitry. This review provides a contemporary update about PTSD, including new data from the clinical and preclinical literature on stress, PTSD, and fear memory consolidation and extinction processes. First, we present an overview of well-established laboratory models of PTSD and discuss their clinical translational value for finding various treatments for PTSD. We then highlight the research progress on the neural circuits of fear and extinction-related behavior, including the prefrontal cortex, hippocampus, and amygdala. We further describe different molecular mechanisms, including GABAergic, glutamatergic, cholinergic, and neurotropic signaling, responsible for the structural and functional changes during fear acquisition and fear extinction processes in PTSD.

Objective: Reverse cholesterol transport, removing excess cholesterol from peripheral tissues, is an important therapeutic target for atherosclerosis treatment. In this study, we propose a new small molecule, E17241, that may be used to treat atherosclerosis by promoting reverse cholesterol transport via ABCA1 (ATP-binding cassette transporter A1) upregulation. Approach and Results: E17241 (4-(1,3-dithiolan-2-yl)-N-(3-hydroxypyridin-2-yl)benzamide) was first identified as an ABCA1 upregulator using a cell-based reporter assay. E17241 significantly increases the mRNA and protein expression levels of ABCA1 in both hepatic cells and macrophages. It promotes cholesterol efflux to apo AI in macrophage cells, and this effect depends on ABCA1. It also decreases total cholesterol content in Ox-LDL (oxidized low-density lipoprotein) loading macrophage cells. E17241 treatment increases the content of ³ H-labeled cholesterol in the feces of male C57BL/6J mice intraperitoneally injected with ³ H-cholesterol-labeled macrophage J774 cells, indicating that it could promote in vivo macrophage reverse cholesterol transport. Compared with the western diet group (western diet–fed male ApoE ^−/− mice), the E17241 group (western diet+E17241 treatment) shows decreased plasma cholesterol, liver cholesterol, and triglyceride levels, with increased fecal cholesterol content. Importantly, E17241 reduces atherosclerotic lesion areas in the en face aorta and aortic sinus while increasing ABCA1 protein levels in both liver and macrophages. Human proteome microarray, coimmunoprecipitation, and other assays demonstrate that PKCζ (protein kinase C zeta) is a binding target of E17241, and this small molecule increases ABCA1 expression in macrophages via the PKCζ-NR (nuclear receptor) pathway. Conclusions: E17241 may be developed as a new lead or drug candidate for the treatment of atherosclerosis by upregulating ABCA1.

Background: Attentional bias plays an important role in sustaining various types of drug addiction. No prior studies examined methamphetamine (MA)-associated psychosis (MAP) relationships between ERP time course and performance on an addiction Stroop task in MA abusers. The aim of the present study was to determine whether MA abusers with (MAP+) or without (MAP-) psychosis exhibit alterations of the ERP during the addiction Stroop task.Methods: Thirty-one healthy controls (CTRL), 14 MAP-, and 24 MAP+ participants were recruited and completed the addiction Stroop task during EEG recording using 32 electrodes. Group variations were compared on measures of behavioral task performance and event-related potentials (ERP) of performance monitoring (N200, P300, N450). The Barratt impulsiveness scores were analyzed to investigate correlations with ERP changes.Results: MA-related word stimulus elicited a more negative N200 amplitude over left-anterior electrodes in MAP- abusers; furthermore, a positive association between the N200 amplitude and Barratt attentional scores and non-planning scores was observed, while no such differences were found in MAP+ abusers. There were no significant differences in reaction time (RT) and error rate between each group.Conclusion: This is the first study to examine psychosis relationships between ERP time course and performance on an addiction Stroop task in MA abusers with or without psychosis. These findings support the association between attentional bias measured by the MA addiction Stroop task and N200 component as well as indicate the possibility of using this cognitive task in combination with ERP technology to detect psychosis factors among abstinent MA abusers.