Discovery of the EL-0052 as a potential anesthetic drug.

As a γ-aminobutyric acid A receptor (GABAR) inhibitor, etomidate fulfills several characteristics of an ideal anesthetic agent, such as rapid onset with rapid clearance and high potency, along with cardiovascular stability. Unfortunately, etomidate has been reported to inhibit CYP11B1 at hypnotic doses, which is associated with a marked increase in patient deaths due to this unexpected off-target effect. In this study, molecular docking was used to simulate the binding mode of etomidate with GABAR and CYP11B1.

Hippocampal CLOCK protein participates in the persistence of depressive-like behavior induced by chronic unpredictable stress.

Rationale: Circadian disturbances are strongly linked with major depression. The circadian proteins CLOCK and BMAL1 are abundantly expressed but function differently in the suprachiasmatic nucleus (SCN) and hippocampus. However, their roles in depressive-like behavior are still poorly understood.

NMDA receptor glycine modulatory site in the ventral tegmental area regulates the acquisition, retrieval, and reconsolidation of cocaine reward memory.

Rationale And Objectives: Accumulating clinical and preclinical studies have shown that the memories of the rewarding effects of drugs and their paired cues may contribute to relapse and persistent cocaine use. Glutaminergic actions in the ventral tegmental area (VTA) have been shown to regulate the rewarding effect of drugs and conditioned responses to drug-associated cues, but the role of the VTA in the acquisition, retrieval, and reconsolidation of cocaine cues is not yet known.

Methods: In the present study, we used 7-chlorothiokynurenic acid (7-CTKA), an N-methyl-D-aspartate (NMDA) receptor glycine modulatory site antagonist with no rewarding effects, to examine the role of the NMDA receptor glycine modulatory site in the acquisition, retrieval, and reconsolidation of cocaine-related reward memory using the conditioned place preference (CPP) paradigm.

Increased Cdk5/p35 activity in the dentate gyrus mediates depressive-like behaviour in rats.

Depression is one of the most pervasive and debilitating psychiatric diseases, and the molecular mechanisms underlying the pathophysiology of depression have not been elucidated. Cyclin-dependent kinase 5 (Cdk5) has been implicated in synaptic plasticity underlying learning, memory, and neuropsychiatric disorders. However, whether Cdk5 participates in the development of depressive diseases has not been examined.

Chronic unpredictable stress induces a reversible change of PER2 rhythm in the suprachiasmatic nucleus.

Many clinical studies have shown that circadian rhythm abnormalities are strongly associated with major depression. The master clock of the circadian system in mammals is located in the suprachiasmatic nucleus (SCN) within the anterior hypothalamus, where Per1 and Per2 are essential core components of circadian rhythm oscillation. Chronic unpredictable stress (CUS) is a reliable animal model of depression with good face, predictive, and constructive validity.

Circadian alteration in neurobiology during protracted opiate withdrawal in rats.

Protracted opiate withdrawal can extend for months of disrupted hormonal circadian rhythms. We examined rodent behaviors and these circadian disturbances in hormone and peptide levels as well as brain clock gene expression during 60 days of protracted withdrawal. Our behavioral tests included open field, elevated plus maze, and sucrose preference tests at 36 h, 10, 30, and 60 days after stopping chronic morphine.

Morphine withdrawal produces circadian rhythm alterations of clock genes in mesolimbic brain areas and peripheral blood mononuclear cells in rats.

Previous studies have shown that clock genes are expressed in the suprachiasmatic nucleus (SCN) of the hypothalamus, other brain regions, and peripheral tissues. Various peripheral oscillators can run independently of the SCN. However, no published studies have reported changes in the expression of clock genes in the rat central nervous system and peripheral blood mononuclear cells (PBMCs) after withdrawal from chronic morphine treatment.