A withdrawal-associated impairment in β-endorphin neurotransmission in the arcuate nucleus (ARC) of the hypothalamus is associated with alcohol dependence characterized by a chronic relapsing disorder. Although acupuncture activates β-endorphin neurons in the ARC projecting to the nucleus accumbens (NAc), a role for ARC β-endorphin neurons in alcohol dependence and acupuncture effects has not been examined. Here, we show that acupuncture at Shenmen (HT7) points attenuates behavioral manifestation of alcohol dependence by activating endorphinergic input to the NAc from the ARC. Acupuncture attenuated ethanol withdrawal tremor, anxiety-like behaviors, and ethanol self-administration in ethanol-dependent rats, which are mimicked by local injection of β-endorphin into the NAc. Acupuncture also reversed the decreased β-endorphin levels in the NAc and a reduction of neuronal activity in the ARC during ethanol withdrawal. These results suggest that acupuncture may provide a novel, potential treatment strategy for alcohol use disorder by direct activation of the brain pathway.
BACKGROUND/OBJECTIVESStromal cell-derived growth factor 1 (SDF-1), also known as chemokine ligand 12, and chemokine receptor type 4 are involved in cancer cell migration. Compound K (CK), a metabolite of protopanaxadiol-type ginsenoside by gut microbiota, is reported to have therapeutic potential in cancer therapy. However, the inhibitory effect of CK on SDF-1 pathway-induced migration of glioma has not yet been established.MATERIALS/METHODSCytotoxicity of CK in C6 glioma cells was determined using an EZ-Cytox cell viability assay kit. Cell migration was tested using the wound healing and Boyden chamber assay. Phosphorylation levels of protein kinase C (PKC)α and extracellular signal-regulated kinase (ERK) were measured by western blot assay, and matrix metallopeptidases (MMP) were measured by gelatin-zymography analysis.RESULTSCK significantly reduced the phosphorylation of PKCα and ERK1/2, expression of MMP9 and MMP2, and inhibited the migration of C6 glioma cells under SDF-1-stimulated conditions.CONCLUSIONSCK is a cell migration inhibitor that inhibits C6 glioma cell migration by regulating its downstream signaling molecules including PKCα, ERK1/2, and MMPs.
Objective : To suggest a scientific evidence of Aconitum carmichaeli Debx. (Aconiti Lateralis Radix Preparata: ALRP) as one of cooling and heating medicines on the regulation of body temperature, we investigated the effects of ALRP water extract on hypothyroidism. Methods : Hypothyroidism was induced by intradermal injection with PTU for 4 weeks in SD rats. ALRP extract or L-thyroxine as a control drug was orally administrated for 2 weeks with PTU injection in rats. The physiological and serological parameters were measured in rats. The histological change of thyroid tissues was observed by H&E staining, and also the expression of thermo-regulating proteins was determined by Western blot in dorsal root ganglia and brain tissues of rats. Results : The administration of ALRP extract in PTU-induced hypothyroidism rats was significantly increased body temperature, but did not changes on body weight, food and water intake. ALRP extract did not effect on the levels of TSH and T4 in the hypothyroidism rats. ALRP extract significantly decreased the levels of GPT, glucose, HDL-cholesterol, LDL-cholesterol, and total cholesterol in the hypothyroidism rats. In histological observation, the enlarged epithelium and atrophic follicles with higher concentration of follicular cells on hypothyroidism were improved by ALRP extract. In addition, ALRP extract increased the expression of TRPV1 and TRPM8 ion channel proteins in hypothyroidism rats. Conclusion : These results indicate that ALRP extract can improve PTU-induced hypothyroidism through regulation of body temperature and lipid accumulation. The action mechanism of ALRP extract is related with body temperature control by thermoregulation with TRP ion channels.
Drug addiction is a chronic relapsing disease, which causes serious social and economic problems. The most important trial for the successful treatment of drug addiction is to prevent the high rate of relapse to drug-seeking behaviors. Opponent process as a motivational theory with excessive drug seeking in the negative reinforcement of drug dependence reflects both loss of brain reward system and recruitment of brain stress system. The negative emotional state produced by brain stress system during drug withdrawal might contribute to the intense drug craving and drive drug-seeking behaviors via negative reinforcement mechanisms. Decrease in dopamine neurotransmission in the nucleus accumbens and recruitment of corticotropin-releasing factor in the extended amygdala are hypothesized to be implicated in mediating this motivated behavior. Also, a brain stress response system is hypothesized to increase drug craving and contribute to relapse to drug-seeking behavior during the preoccupation and anticipation stage of dependence caused by the exposure to stress characterized as the nonspecific responses to any demands on the body. Acupuncture has proven to be effective for reducing drug addiction and stress-related psychiatric disorders, such as anxiety and depression. Furthermore, acupuncture has been shown to correct reversible brain malfunctions by regulating drug addiction and stress-related neurotransmitters. Accordingly, it seems reasonable to propose that acupuncture attenuates relapse to drug-seeking behavior through inhibition of stress response. In this review, a brief description of stress in relapse to drug-seeking behavior and the effects of acupuncture were presented.
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