ABSTRACT
Opiates produce a strong rewarding effect, but abstinence from opiate use emerges with severe negative emotions. Depression is one of the most frequent emotion disorders associated with opiate abstinence, which is thought to be a main cause for relapse. However, neurobiological bases of such an aversive emotion processing are poorly understood. Here, we find that morphine abstinence activates κ-opioid receptors (KORs) by increasing endogenous KOR ligand dynorphin expression in the amygdala, which in turn facilitates glutamate transporter 1 (GLT1) expression by activation of p38 mitogen-activated protein kinase (MAPK). Upregulation of GLT1 expression contributes to opiate-abstinence-elicited depressive-like behaviors through modulating amygdalar glutamatergic inputs to the nucleus accumbens (NAc). Intra-amygdala injection of GLT1 inhibitor DHK or knockdown of GLT1 expression in the amygdala significantly suppresses morphine-abstinence-induced depressive-like behaviors. Pharmacological and pharmacogenetic activation of amygdala-NAc projections prevents morphine-abstinence-induced behaviors. Overall, our study provides key molecular and circuit insights into the mechanisms of depression associated with opiate abstinence.
Subject(s)
Amygdala/metabolism , Behavior, Animal , Depression/metabolism , Glucose Transporter Type 1/metabolism , Glutamic Acid/metabolism , Morphine , Nucleus Accumbens/metabolism , Receptors, Opioid, kappa/metabolism , Substance Withdrawal Syndrome/metabolism , Amygdala/physiopathology , Animals , Depression/chemically induced , Depression/physiopathology , Depression/psychology , Disease Models, Animal , Dynorphins/metabolism , Excitatory Postsynaptic Potentials , Glucose Transporter Type 1/genetics , Male , Mice, Inbred C57BL , Mice, Knockout , Neural Pathways/metabolism , Neural Pathways/physiopathology , Nucleus Accumbens/physiopathology , Receptors, Opioid, kappa/genetics , Signal Transduction , Substance Withdrawal Syndrome/physiopathology , Substance Withdrawal Syndrome/psychology , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Metal tungstates, expressed by the general formula of MWO4, have important properties and applications in photoluminescence, microwave applications, optical fibers, scintillator materials, humidity sensors, magnetic properties, and catalysts. In this paper, we report a successful synthesis of CaWO4:Eul+ crystals with various morphologies in mild hydrothermal conditions with surfacntant including sodium citrate, CTAB, PEG and citrate acid (CA). The formation of the crystals are strongly dependent on the employment of surfactant. The surfactant concentration has been found significant influence in the resulting morphologies due to different properties of each one. Extensive characterization have been performed by using X-ray diffraction (XRD), field emission scanning electron microscope (FE-SEM) in search of the formation mechanism of multi-morphological CaWO4:Eu3+ crystals. The growth mechanism of monodispersed CaWO4:EuS+ crystal are proposed. And the photoluminescence properties were investigated.
ABSTRACT
To research the intestinal toxicity of n-BuOH fraction in Phytolacca Radix before and after being processed with vinegar. Toxic n-BuOH fractions were separated from Phytolacca Radix. In the animal model, the level of intestinal edema, water content of intestine and stool, IC50 values of HT-29 and IEC-6 were detected with MTT method to compare the changes in toxicity of n-BuOH fractions from Phytolacca Radix before and after being processed with vinegar. n-BuOH fractions of Phytolacca Radix could cause intestinal edema in mice, increase the edema of duodenum, jejunum and the water content in stool, inhibit the proliferation of HT-29 cells and IEC-6 cells, indicating its intestinal toxicity, with HT-29 IC50 at 14.59 mgâ¢L⻹ and IEC-6 IC50 at 43.77 mgâ¢L⻹. After being processed with vinegar, the level of intestinal edema, edema of duodenum and jejunum and the water content in stool and inhibition ratio of cells line were reduced, with HT-29 IC50 at 58.51 mgâ¢L⻹ and IEC-6 IC50 at 84.37 mgâ¢L⻹. After being processed with vinegar, the toxicity of n-BuOH fractions from Phytolacca Radix decreased obviously.
Subject(s)
Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/isolation & purification , Edema/drug therapy , Phytolacca/chemistry , Acetic Acid/chemistry , Animals , Chemistry, Pharmaceutical , Drugs, Chinese Herbal/chemistry , Edema/immunology , Humans , Intestines/drug effects , Intestines/immunology , Male , Mice , Mice, Inbred ICR , Plant Roots/chemistryABSTRACT
This study was to investigate the mechanism of gingerols antagonizing the inflammatory effect of toxic raphides from Pinella pedatisecta. Mice peritonitis models induced by toxic raphides from P. pedatisecta were applied to observe the effect of gingerols on inflammatory mediators PGE2 in the exudates of abdominal inflammation in mice; rats peritoneal macrophage in vitro culture models were adopted to study the anti-inflammatory effects of gingerol against toxic raphides, with TNF-α and IL-1ß in supernatant as indexes. Scanning electron microscopy was used to observe the changes in surface morphology of macrophages treated by raphides and gingerols. Macrophages-neutrophils co-cultured models were used to study the antagonism of gingerols against the effect of toxic raphides' stimulation on neutrophils migration. Results showed that gingerols could significantly inhibit the production of PGE2 in the exudates of abdominal inflammation induced by toxic raphides from P. pedatisecta in mice. Gingerols could significantly inhibit the toxic raphides from P. pedatisecta to induce the release of inflammatory factors, with certain dose dependence. Scanning electron microscopy showed that gingerols could significantly inhibit phagocytosis of macrophages, cytomembrane injury, and neutrophils migration induced by toxic raphides from P. pedatisecta. The results showed that the antagonism mechanism of gingerols against the toxic raphides from P. pedatisecta may be associated with inhibiting the pro-inflammatory toxicity including macrophage activation, inflammatory factors release, and neutrophils migration.
Subject(s)
Anti-Inflammatory Agents/administration & dosage , Catechols/antagonists & inhibitors , Drugs, Chinese Herbal/toxicity , Fatty Alcohols/antagonists & inhibitors , Inflammation/drug therapy , Pinellia/toxicity , Animals , Catechols/administration & dosage , Disease Models, Animal , Drug Antagonism , Fatty Alcohols/administration & dosage , Humans , Inflammation/etiology , Inflammation/immunology , Interleukin-1beta/immunology , Macrophages/drug effects , Macrophages/immunology , Male , Mice , Mice, Inbred ICR , Neutrophils/drug effects , Neutrophils/immunology , Phagocytosis/drug effects , Pinellia/chemistry , Rats , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/immunologyABSTRACT
To look for the toxicity fraction of Euphorbia pekinensis and discuss the vinegar processing mechanism. The level of intestinal edema, water content of intestine and stool, IC50 values of IEC-6 were applied to evaluate the toxicity of different fractions. RT-PCR was employed for detecting AQP1, AQP3 mRNA expression. The petroleum ether (PE) fraction and ethyl acetate (EtOAc) fraction could significant cause intestinal edema in mice, increase the water content of duodenum, colon and stool, inhibited the mRNA expression of AQP1 and increased the mRNA level of AQP3 in colon, and the petroleum ether (PE) fraction was more poisonous. After the petroleum ether (PE) fraction was processed with vinegar, the level of intestinal edema, water content of duodenum, colon, stool and inhibition ratio of cells line were reduced. And we compared the composition change after vinegar processing, finding that the conpekinensis.
