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Background: Our previous studies proved that neurogenic inflammatory spots (or neurogenic spots) have the same physiological features as acupuncture points and that neurogenic spot stimulation generates therapeutic effects in various animal models. However, it is unclear how deeply the neurogenic spots should be stimulated to generate therapeutic effects. Methods: The effects of acupuncture at various needle depths below the neurogenic spot were examined in a rat immobilization stress-induced hypertension (IMH) model. Electroacupuncture was applied to a neurogenic spot at depths of 1, 2, or 3 mm using a concentric bipolar electrode. Results: Electrical stimulation of the neurogenic spot at a 3-mm depth most effectively lowered blood pressure compared with controls and stimulation at 1- and 2-mm depths, which was inhibited by pretreatment with a local anesthetic lidocaine. Electrical stimulation of the neurogenic spot or injection of substance P (SP) at a 3-mm depth significantly excited the rostral ventrolateral medulla (rVLM) compared with superficial stimulation. Electrical stimulation applied at a 3-mm depth on neurogenic spots dominantly caused c-fos expression from rVLM and ventrolateral periaqueductal gray (vlPAG) in IMH rats. Pretreatment with resiniferatoxin (RTX) injection into the neurogenic spot to ablate SP or calcitonin gene-related peptide (CGRP) prevented the effects of 3-mm neurogenic spot stimulation on blood pressure in IMH rats. Conversely, artificial injection of SP or CGRP generated anti-hypertensive effects in IMH rats. Conclusion: Our data suggest that neurogenic spot stimulation at a 3-mm depth generated anti-hypertensive effects through the local release of SP and CGRP and activation of rVLM and vlPAG.
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BACKGOUND: Pyeongwi-san (PWS) is a widely used formula for treating digestive disorders in Korea and China. Inflammatory bowel disease (IBD) is characterized by progressive inflammation of the gastrointestinal tract. Emerging evidence supports the protective effect of PWS against IBD, but specific mechanisms are still elusive. METHODS: Active compounds of PWS were screened from the medicinal materials and chemical compounds in Northeast Asian traditional medicine (TM-MC) in the consideration of drug-likeness and oral bioavailability. Target candidates of active compounds were predicted using the ChEMBL database. IBD-related targets were obtained from the GeneCards and DisGeNET databases. The network of composition-targets-disease was constructed. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed. Molecular docking was used to simulate the binding affinity of active compounds on target proteins and molecular dynamics was used to validate the molecular docking result. RESULTS: A total of 26 core target proteins of PWS were related to IBD. Enrichment analysis suggested that PWS is highly associated with tumor necrosis factor signaling pathway, apoptosis, and the collapse of tight junctions. Moreover, molecular docking and molecular dynamics simulation proposed ß-eudesmol and (3R,6R,7S)-1,10-bisaboladien-3-ol to ameliorate IBD through the binding to TNF and MMP9, respectively. CONCLUSION: Present in silico analysis revealed potential pathways and insight of PWS to regulate IBD. These results imply that the therapeutic effect of PWS might be achieved via an inhibitory effect.
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The medial prefrontal cortex (mPFC) and the lateral habenula (LHb) play roles in drug addiction and cognitive functions. Our previous studies have suggested that acupuncture at Shenmen (HT7) points modulates mesolimbic reward system in order to suppress drug-induced addiction behaviours. To explore whether an mPFC-LHb circuit mediates the inhibitory effects of acupuncture on addictive behaviours, we examined the projection from mPFC to LHb, excitation of mPFC neurons during acupuncture stimulation, the effects of optogenetic modulation of mPFC-LHb on HT7 inhibition of cocaine-induced locomotion and the effect of mPFC lesion on HT7 inhibition of nucleus accumbens (NAc) dopamine release. Acupuncture was applied at bilateral HT7 points for 20 s, and locomotor activity was measured in male Sprague-Dawley rats. Although cocaine injection significantly increased locomotor activity, HT7 acupuncture suppressed the cocaine-induced locomotion. The inhibitory effect of HT7 on cocaine-enhanced locomotion was blocked by optogenetic silencing of the mPFC-LHb circuit. In vivo extracellular recordings showed that HT7 acupuncture evoked an increase in the action potentials of mPFC neurons. Optopatch experiment proved glutamatergic projections from mPFC to LHb. HT7 acupuncture suppressed NAc dopamine release following cocaine injection, which was blocked by electrolytic lesion of mPFC. These results suggest the mediation of mPFC-LHb circuit in the inhibitory effects of acupuncture on cocaine psychomotor activity in rats.
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Terapia por Acupuntura , Cocaína , Habénula , Masculino , Animales , Ratas , Ratas Sprague-Dawley , Dopamina , Corteza Prefrontal , Cocaína/farmacologíaRESUMEN
Introduction: We and others have shown that electrical stimulation of the PC-6 acupoint over the wrist relieves hypertension by stimulating afferent sensory nerve fibers and activating the central endogenous opioid system. Warm needle acupuncture has long been utilized to treat various diseases in clinics. Methods: Here, we developed a temperature-controllable warm needle acupuncture instrument (WAI) and investigated the peripheral mechanism underlying the effect of warm needle acupuncture at PC-6 on hypertension in a rat model of immobilization stress-induced hypertension. Results: Stimulation with our newly developed WAI and traditional warm needle acupuncture attenuated hypertension development. Such effects were reproduced by capsaicin (a TRPV1 agonist) injection into PC-6 or WAI stimulation at 48°C. In contrast, PC-6 pretreatment with the TRPV1 antagonist capsazepine blocked the antihypertensive effect of WAI stimulation at PC-6. WAI stimulation at PC-6 increased the number of dorsal root ganglia double-stained with TRPV1 and CGRP. QX-314 and capsaicin perineural injection into the median nerve for chemical ablation of small afferent nerve fibers (C-fibers) prevented the antihypertensive effect of WAI stimulation at PC-6. Additionally, PC-6 pretreatment with RTX ablated the antihypertensive effect of WAI stimulation. Conclusion: These findings suggest that warm needle acupuncture at PC-6 activates C-fiber of median nerve and the peripheral TRPV1 receptors to attenuate the development of immobilization stress-induced hypertension in rats.
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Adolescent cocaine exposure (ACE) increases risk of developing psychiatric problems such as anxiety, which may drive relapse in later life, however, its underlying molecular mechanism remains poorly understood. Methods: ACE male mice model were established by exposing to cocaine during adolescent period. Elevated plus maze (EPM) were used to assess anxiety-like behaviors in mice. Within claustrum, local injection of SCH-23390, a specific antagonist for dopamine receptor 1 (D1R), or D1R knocking-down virus were used to regulate D1R function or expression on CaMKII-positive neurons (D1RCaMKII) in vivo. Electro-acupuncture (EA) treatment was performed at acupoints of Baihui and Yintang during withdrawal period. Results: We found that ACE mice exhibited anxiety-like behaviors, along with more activated CaMKII-positive neurons and increased D1RCaMKII levels in claustrum during adulthood. Inhibiting D1R function or knocking-down D1RCaMKII levels in claustrum efficiently reduced claustrum activation, and ultimately suppressed anxiety-like behaviors in ACE mice during adulthood. EA treatment alleviated ACE-evoked claustrum activation and anxiety-like behaviors by suppressing claustrum D1RCaMKII. Conclusion: Our findings identified a novel role of claustrum in ACE-induced anxiety-like behaviors, and put new insight into the D1RCaMKII in the claustrum. The claustrum D1RCaMKII might be a promising pharmacological target, such as EA treatment, to treat drug-induced anxiety-like behaviors.
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Claustro , Cocaína , Ratones , Masculino , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Claustro/metabolismo , Cocaína/metabolismo , Cocaína/farmacología , Neuronas/metabolismo , Ansiedad/inducido químicamente , Ansiedad/terapia , Receptores de Dopamina D1/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Lythrum salicaria L., also called purple loosestrife, has traditionally been used as a medicinal plant to treat internal dysfunction, such as gastrointestinal disorders or hemorrhages. It contains numerous phytochemical compounds, including orientin, and has been reported to have anti-diarrheal, anti-inflammatory, antioxidant, and antimicrobial properties. AIM OF THE STUDY: The effects of Lythrum salicaria L. on obesity have not been explored. Therefore, we investigated the anti-obesity effects of Lythri Herba, the aerial part of this plant, in vitro and in vivo. MATERIALS AND METHODS: Using distilled water, Lythri Herba water extracts (LHWE) were prepared by extracting Lythri Herba at 100°Ï¹. The contents of orientin in LHWE were identified using High Performance Liquid Chromatography (HPLC) analysis. To evaluate the anti-obesity effect of LHWE, 3T3-L1 adipocytes and a high-fat diet (HFD)-fed mice were used. Oil-red O staining was performed to examine the anti-adipogenic effects of LHWE in vitro. The histological changes in epididymal white adipose tissue (epiWAT) by LHWE were examined using hematoxylin and eosin staining. Serum leptin levels were measured by enzyme-linked immunosorbent assay. Specific quantification kits measured total cholesterol and triglyceride levels in the serum. The relative fold induction of protein and mRNA was determined using western blot and Quantitative real-time Polymerase Chain Reaction analysis, respectively. RESULTS: HPLC analysis demonstrated the presence of orientin in LHWE. LHWE treatment markedly reduced lipid accumulation in differentiated 3T3-L1 adipocytes. LHWE administration also conferred resistance to HFD-induced weight gain in mice and reduced epiWAT mass. Mechanistically, LHWE significantly decreased lipogenesis by downregulating lipoprotein lipase (LPL), glucose-6-phosphate dehydrogenase, ATP-citrate lyase, fatty acid synthase, stearoyl-CoA desaturase 1, sterol regulatory element binding transcription factor 1, and carbohydrate response element binding protein expression and increased the expression of genes involved in fatty acid oxidation (FAO), peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase 1 in 3T3-L1 adipocytes and epiWAT. Furthermore, LHWE significantly up-regulated the phosphorylation of AMP-activated protein kinase in 3T3-L1 adipocytes and epiWAT. CONCLUSION: LHWE decreases white adipogenesis in vitro and HFD-induced weight gain in vivo, which is associated with reduced lipogenesis and enhanced FAO.
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Fármacos Antiobesidad , Agua , Ratones , Animales , Agua/farmacología , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/uso terapéutico , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Metabolismo de los Lípidos , Aumento de Peso , Adipogénesis , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Células 3T3-L1 , Dieta Alta en Grasa/efectos adversos , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Mechanoreceptor activation modulates GABA neuron firing and dopamine (DA) release in the mesolimbic DA system, an area implicated in reward and substance abuse. The lateral habenula (LHb), the lateral hypothalamus (LH), and the mesolimbic DA system are not only reciprocally connected, but also involved in drug reward. We explored the effects of mechanical stimulation (MS) on cocaine addiction-like behaviors and the role of the LH-LHb circuit in the MS effects. MS was performed over ulnar nerve and the effects were evaluated by using drug seeking behaviors, optogenetics, chemogenetics, electrophysiology and immunohistochemistry. RESULTS: Mechanical stimulation attenuated locomotor activity in a nerve-dependent manner and 50-kHz ultrasonic vocalizations (USVs) and DA release in nucleus accumbens (NAc) following cocaine injection. The MS effects were ablated by electrolytic lesion or optogenetic inhibition of LHb. Optogenetic activation of LHb suppressed cocaine-enhanced 50 kHz USVs and locomotion. MS reversed cocaine suppression of neuronal activity of LHb. MS also inhibited cocaine-primed reinstatement of drug-seeking behavior, which was blocked by chemogenetic inhibition of an LH-LHb circuit. CONCLUSION: These findings suggest that peripheral mechanical stimulation activates LH-LHb pathways to attenuate cocaine-induced psychomotor responses and seeking behaviors.
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Trastornos Relacionados con Cocaína , Cocaína , Habénula , Humanos , Trastornos Relacionados con Cocaína/terapia , Trastornos Relacionados con Cocaína/metabolismo , Habénula/metabolismo , Cocaína/farmacología , Cocaína/metabolismo , Neuronas , Dopamina/metabolismo , Dopamina/farmacología , Hipotálamo/metabolismoRESUMEN
Background and aim: It has been reported that acupuncture at GB34 can enhance neurogenesis in the subventricular zone (SVZ) of mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, the signaling pathway that plays a critical role in neurogenesis needs to be established. Herein, we investigated the neurogenesis-promoting pathway mediated by acupuncture, focusing on extracellular signal-regulated kinase (ERK) signaling. Experimental procedure: Male 10-week-old C57BL/6 mice were intraperitoneally injected with 30 mg/kg MPTP once daily for 5 days. Subsequently, mice were intraperitoneally injected with 50 mg/kg bromodeoxyuridine (BrdU), and electroacupuncture (EA) was performed at GB34 and BL60 for 3 weeks. The survival of dopaminergic neurons in the nigrostriatal pathway, cell proliferation in the SVZ, and expression levels of brain-derived neurotrophic factor (BDNF) and phosphorylated ERK (pERK) were evaluated. Results and conclusion: MPTP induced dopaminergic neuronal death in the nigrostriatal pathway, and reduced the number of BrdU-positive and BrdU/doublecortin double-positive cells in the SVZ; these parameters were restored by EA. Moreover, EA prevented MPTP-induced reduction in striatal expression of BDNF and pERK. These results indicate that EA could prevent dopaminergic neuronal death in the nigrostriatal pathway and restore neurogenesis in the SVZ, which may be attributed to the activation of the BDNF-ERK pathway.
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Odd-chain saturated fatty acids generally serve as specific biomarkers of dietary components and dairy intake, some of which have anticancer properties. This study was performed to assess the anticancer effects of heptadecanoic acid (HDNA) in human pancreatic carcinoma cells. MTT (thiazolyl blue tetrazolium bromide) assay showed that HDNA exerted stronger cytotoxic effects than pentadecanoic acid, palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), and linoleic acid (18:2) on both Panc-1 and MIA PaCa-2 pancreatic cancer cells. In addition, HDNA reduced colony formation and induced apoptosis in these pancreatic cancer cells as indicated by Hoechst 33342 staining, Annexin V/propidium iodide staining, cell cycle analysis, and Western blotting analysis in a dose-dependent manner. Moreover, HDNA synergistically reduced cell viability and promoted apoptosis when combined with gemcitabine (GEM), a chemotherapeutic agent commonly used in the treatment of pancreatic cancer. GEM-resistant MIA PaCa-2 (GR-MIA PaCa-2) cells with a resistance indices (RI) value of 215.09 [RI = half-maximal inhibitory concentration (IC50) of GR-MIA PaCa-2 cells/IC50 of MIA PaCa-2 cells] were established, and the efficacy of HDNA on GEM chemosensitivity was confirmed. Surprisingly, HDNA exhibited even higher antiproliferative efficacy against GR-MIA PaCa-2 cells (IC50 = 71.45 ± 6.37 µM) than parental MIA PaCa-2 cells (IC50 = 77.47 ± 2.10 µM). Finally, HDNA treatment inhibited the Hippo pathway and induced apoptosis of GR-MIA PaCa-2 cells. These findings suggest the beneficial effects of a HDNA-rich diet during pancreatic cancer treatments.
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Gemcitabina , Neoplasias Pancreáticas , Humanos , Proliferación Celular , Línea Celular Tumoral , Neoplasias Pancreáticas/genética , Ácidos Grasos/farmacología , Apoptosis , Neoplasias PancreáticasRESUMEN
Objectives: A powerful analgesic called Morphine causes addiction behaviors and immune suppression as a potential oxidative stressor. Acupuncture showed to inhibit oxidative stress-induced hepatic damage, regulate reactive oxygen species, and attenuate morphine addiction behaviors. Therefore, we investigated the potential effects of acupuncture on morphine-induced immune suppression. Materials and Methods: Rats received morphine intravenously through implanted catheters for 3, 7, or 21 days to determine the optimal condition for morphine-induced immune suppression. Second, we examined whether intravenous (iv.) or intraperitoneal (ip.) administration produced different results. Third, the effects of acupuncture in rats who received morphine for 21 days were investigated. Spleen and submandibular lymph node (S-LN) weights and natural killer (NK) cell activity were measured, and the white pulp diameter, total and cortical spleen thicknesses, and the number of lymphoid follicles in S-LNs were examined. The number of immunoreactive cells was also measured. Results: Decreased organ weights and increased atrophic changes were observed as morphine-induced immune suppression. However, dose-dependent increased immune suppression was not observed between 5.0 mg/kg and 10.0 mg/kg of morphine. And, 3-day withdrawal did not affect. Similar histopathological findings were observed in 5.0 and 10.0 ip. rats when compared to equal dosages of iv., respectively. The morphine induced-immune suppression evidenced by spleen and left S-LN weights, splenic NK cell activities, histopathological findings, and the immunoreactive cell number were normalized by acupuncture. Conclusion: These results indicate that acupuncture inhibits morphine-induced immune suppression, maybe via antioxidative action.
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Therapeutic activation of mechanoreceptors (MStim) in osteopathy, chiropractic and acupuncture has been in use for hundreds of years with a myriad of positive outcomes. It has been previously shown to modulate the firing rate of neurons in the ventral tegmental area (VTA) and dopamine (DA) release in the nucleus accumbens (NAc), an area of interest in alcohol-use disorder (AUD). In this study, we examined the effects of MStim on VTA GABA neuron firing rate, DA release in the NAc, and behavior during withdrawal from chronic EtOH exposure in a rat model. We demonstrate that concurrent administration of MStim and EtOH significantly reduced adaptations in VTA GABA neurons and DA release in response to a reinstatement dose of EtOH (2.5 g/kg). Behavioral indices of EtOH withdrawal (rearing, open-field crosses, tail stiffness, gait, and anxiety) were substantively ameliorated with concurrent application of MStim. Additionally, MStim significantly increased the overall frequency of ultrasonic vocalizations, suggesting an increased positive affective state.
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Dopamina , Área Tegmental Ventral , Ratas , Animales , Dopamina/farmacología , Neuronas GABAérgicas , Etanol/farmacología , Núcleo AccumbensRESUMEN
OBJECTIVE: Mitophagy is known to contribute towards progression of Parkinson's disease. Korean red ginseng (KRG) is a widely used medicinal herb in East Asia, and recent studies have reported that KRG prevents 1-methyl-4-phenylpyridinium ion (MPP+)-induced cell death. This study was undertaken to investigate whether KRG suppresses MPP+-induced apoptosis and mitophagy. METHODS: SH-SY5Y cells were incubated with KRG for 24 h, and subsequently exposed to MPP+. The MPP+-induced cell death was confirmed with the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. Changes in the structure and function of mitochondria were confirmed using mitotracker, MitoSOX red mitochondrial superoxide indicator, parkin, and phosphatase and tensin homolog deleted on chromosome ten-induced putative kinase 1 (PINK1) immunofluorescent staining. Western blotting was performed to evaluate the expression of apoptosis-related factors in whole cells, including Bax, Bcl-2 and cleaved caspase-3, and mitophagy-related factors in the mitochondrial fraction, including cytochrome c, parkin, PINK1, translocase of the outer membrane 20 (TOM20), p62 and Beclin 1. RESULTS: MPP+ induced cell death by cytochrome c release and caspase-3 activation; however, this effect was suppressed by KRG's regulation of the expressions of Bcl-2 and Bax. Moreover, MPP+ exposure increased the mitochondrial expressions of parkin, PINK1, Beclin 1 and p62, and decreased TOM20, cytochrome c and Bcl-2 expressions. These MPP+-induced changes in the mitochondrial fraction were attenuated by treatment with KRG. CONCLUSION: KRG effectively prevents MPP+-induced SH-SY5Y cell death by regulating cytochrome c release from mitochondria and PINK1/parkin-mediated mitophagy, through regulation of the Bcl-2 family.
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1-Metil-4-fenilpiridinio , Mitofagia , Panax , 1-Metil-4-fenilpiridinio/toxicidad , Apoptosis , Línea Celular Tumoral , Humanos , Mitocondrias , Panax/química , Especies Reactivas de OxígenoRESUMEN
The essential microelement zinc plays immunoregulatory roles via its ability to influence signaling pathways. Zinc deficiency impairs overall immune function and resultantly increases susceptibility to infection. Thus, zinc is considered as an immune-boosting supplement for populations with hypozincemia at high-risk for infection. Besides its role as a structural cofactor of many proteins, zinc also acts as an intracellular messenger in immune cell signaling. T-cell activation instructs zinc influx from extracellular and subcellular sources through the Zip6 and Zip8 zinc transporters, respectively. Increased cytoplasmic zinc participates in the regulation of T-cell responses by modifying activation signaling. However, the mechanism underlying the activation-dependent movement of zinc ions by Zip transporters in T cells remains elusive. Here, we demonstrate that Zip6, one of the most abundantly expressed Zip transporters in T cells, is mainly localized to lipid rafts in human T cells and is recruited into the immunological synapse in response to TCR stimulation. This was demonstrated through confocal imaging of the interaction between CD4+ T cells and antigen-presenting cells. Further, immunoprecipitation assays show that TCR triggering induces tyrosine phosphorylation of Zip6, which has at least three putative tyrosine motifs in its long cytoplasmic region, and this phosphorylation is coupled with its physical interaction with Zap70. Silencing Zip6 reduces zinc influx from extracellular sources and suppresses T-cell responses, suggesting an interaction between Zip6-mediated zinc influx and TCR activation. These results provide new insights into the mechanism through which Zip6-mediated zinc influx occurs in a TCR activation-dependent manner in human CD4+ T cells.
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Células Presentadoras de Antígenos/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Proteínas de Transporte de Catión/metabolismo , Sinapsis Inmunológicas/metabolismo , Microdominios de Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Receptores de Antígenos de Linfocitos T/metabolismo , Proteína Tirosina Quinasa ZAP-70/metabolismo , Células Presentadoras de Antígenos/inmunología , Linfocitos T CD4-Positivos/inmunología , Proteínas de Transporte de Catión/genética , Humanos , Sinapsis Inmunológicas/inmunología , Células Jurkat , Activación de Linfocitos , Microdominios de Membrana/inmunología , Proteínas de Neoplasias/genética , Fosforilación , Transducción de Señal , TirosinaRESUMEN
Acupuncture affects the central nervous system via the regulation of neurotransmitter transmission. We previously showed that Shemen (HT7) acupoint stimulation decreased cocaine-induced dopamine release in the nucleus accumbens. Here, we used the intracranial self-stimulation (ICSS) paradigm to evaluate whether HT stimulation regulates the brain reward function of rats. We found that HT stimulation triggered a rightward shift of the frequency-rate curve and elevated the ICSS thresholds. However, HT7 stimulation did not affect the threshold-lowering effects produced by cocaine. These results indicate that HT7 points only effectively regulates the ICSS thresholds of the medial forebrain bundle in drug-naïve rats.
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Terapia por Acupuntura/métodos , Cocaína/administración & dosificación , Estimulación Eléctrica/métodos , Haz Prosencefálico Medial/fisiología , Recompensa , Autoestimulación/fisiología , Anestésicos Locales/administración & dosificación , Animales , Masculino , Haz Prosencefálico Medial/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Autoestimulación/efectos de los fármacosRESUMEN
Acupuncture modulates the mesolimbic dopamine (DA) system; an area implicated in drug abuse. However, the mechanism by which peripheral sensory afferents, during acupuncture stimulation, modulate this system needs further investigation. The lateral hypothalamus (LH) has been implicated in reward processing and addictive behaviors. To investigate the role of the LH in mediating acupuncture effects, we evaluated the role of LH and spinohypothalamic neurons on cocaine-induced psychomotor activity and NAc DA release. Systemic injection of cocaine increased locomotor activity and 50 kHz ultrasonic vocalizations (USVs), which were attenuated by mechanical stimulation of needles inserted into HT7 but neither ST36 nor LI5. The acupuncture effects were blocked by chemical lesions of the LH or mimicked by activation of LH neurons. Single-unit extracellular recordings showed excitation of LH and spinohypothalamic neurons following acupuncture. Our results suggest that acupuncture recruits the LH to suppress the mesolimbic DA system and psychomotor responses following cocaine injection.
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Cocaína/farmacología , Dopamina/metabolismo , Neuronas Aferentes/metabolismo , Trastornos Relacionados con Sustancias/metabolismo , Acupuntura/métodos , Animales , Humanos , Área Hipotalámica Lateral/efectos de los fármacos , Área Hipotalámica Lateral/metabolismo , Locomoción/efectos de los fármacos , Agujas , Neuronas Aferentes/efectos de los fármacos , Neuronas Aferentes/patología , Ratas , Trastornos Relacionados con Sustancias/fisiopatología , Trastornos Relacionados con Sustancias/terapiaRESUMEN
The rostromedial tegmental nucleus (RMTg), a GABAergic afferent to midbrain dopamine (DA) neurons, has emerged as an integral player in both rewarding and nociceptive responses. While previous studies have demonstrated that acupuncture modulates DA transmission in the mesolimbic reward system originating in the ventral tegmental area (VTA) and projecting to the nucleus accumbens (NAc) and can reduce drug self-administration, the central links between peripheral acupuncture signals and brain reward systems are not well-characterized. Thus, we hypothesised that acupuncture would elicit inhibitory signals from RMTg neurons to brain reward systems. Acupuncture reduced acute cocaine-induced locomotor activity and DA release in a point-specific manner, which was blocked by optogenetic silencing or chemical lesion of the RMTg. The acupuncture effect was mimicked by chemical activation of the RMTg. Acupuncture activated RMTg GABA neurons. In addition, the inhibitory effects of acupuncture on acute cocaine-induced locomotor activity were prevented by electrolytic lesions of the lateral habenula (LHb) or fasciculus retroflexus (FR), areas known to project to the RMTg. These findings suggest that acupuncture recruits the RMTg to reduce the psychomotor responses enhanced by acute cocaine.
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Terapia por Acupuntura/métodos , Cocaína/farmacología , Desempeño Psicomotor/efectos de los fármacos , Desempeño Psicomotor/fisiología , Tegmento Mesencefálico/metabolismo , Animales , Neuronas GABAérgicas/metabolismo , Masculino , Núcleo Accumbens/metabolismo , Ratas , Ratas Sprague-Dawley , Recompensa , Área Tegmental Ventral/metabolismoRESUMEN
Both the positive (manifested by locomotor sensitization) and negative (withdrawal symptoms) reinforcing effects of ethanol (EtOH) involve central nitric oxide (NO) signaling. Sauchinone (a bioactive lignan in Saururus chinensis) has been shown to improve methamphetamine-induced behavioral and neurochemical changes via the NO signaling pathway. Thus, this study evaluated the effects of sauchinone on locomotor sensitization and anxiety during EtOH withdrawal (EtOHW). Male adult Sprague-Dawley rats were treated with 1.5 g/kg/day of EtOH (20%, vol/vol) via intraperitoneal injection for 28 days, followed by a 3-day withdrawal. During withdrawal, the rats were given intragastric sauchinone (2.5, 7.5, or 25 mg/kg/day) once a day. EtOH locomotor sensitization was determined by challenging EtOHW rats with 0.75 g/kg EtOH, while EtOHW-induced anxiety was assessed using the elevated plus maze (EPM). None of the three doses of sauchinone affected EtOH locomotor sensitization. However, in the EPM, treatment of EtOHW rats with sauchinone at 7.5 or 25 mg/kg/day increased both the number of entries into and the time spent in the open arms. Moreover, the two doses of sauchinone inhibited the oversecretion of plasma corticosterone during EtOHW. In the bed nucleus of the stria terminalis (BNST), EtOHW increased NO production, enhanced gene and protein expression of both inducible nitric oxide synthase (iNOS) and neuronal NOS (nNOS), and also elevated protein levels of corticotropin-releasing factor, which were all inhibited by 25 mg/kg/day sauchinone. In an in vitro experiment, sauchinone (3, 10, and 30 µM) inhibited H2O2-stimulated nNOS protein expression in neuronal PC12 cells. Finally, intra-BNST infusion of sodium nitroprusside, a NO donor, after sauchinone (25 mg/kg/day) administration, abolished its expected anxiolytic effect. Taken together, these results indicate that sauchinone attenuates anxiety-like behavior in rats during EtOHW but spares EtOH locomotor sensitization, and the anxiolytic effect is mediated via the NO signaling pathway in the BNST.
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Drug addiction is a chronically relapsing disorder, affecting people from all walks of life. Studies of acupuncture effects on drug addiction are intriguing in light of the fact that acupuncture can be used as a convenient therapeutic intervention for treating drug addiction by direct activation of brain pathway. The current review aims to discuss the neurobiological mechanisms underlying acupuncture's effectiveness in the treatment of drug addiction, on the basis of two different theories (the incentive sensitization theory and the opponent process theory) that have seemingly opposite view on the role of the mesolimbic reward pathways in mediating compulsive drug-seeking behavior. This review provides evidence that acupuncture may reduce relapse to drug-seeking behavior by regulating neurotransmitters involved in drug craving modulation via somatosensory afferent mechanisms. Also, acupuncture normalizes hyper-reactivity or hypoactivity of the mesolimbic dopamine system in these opposed processes in drug addiction, suggesting bidirectional role of acupuncture in regulation of drug addiction. This proposes that acupuncture may reduce drug craving by correcting both dysfunctions of the mesolimbic dopamine pathway.
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Terapia por Acupuntura , Trastornos Relacionados con Sustancias , Comportamiento de Búsqueda de Drogas , Humanos , Motivación , Recompensa , Trastornos Relacionados con Sustancias/terapiaRESUMEN
This study aimed to verify the efficacy of a combined treatment of Jakyakgamcho-tang (JGT) and acupuncture (CV12, ST25, CV4) on colitis induced by dextrane sulfate sodium (DSS). Changes in immuno-mediated factors and metabolites were investigated. Colitis symptoms such as body weight loss and elevated disease activity index were alleviated by the combined treatment. Moreover, treatment with JGT and acupuncture restored the disturbed architecture of colon by suppressing inflammatory cytokine levels of IFN-[Formula: see text] ([Formula: see text] < 0.05), IL-5 ([Formula: see text] < 0.05), and IL-13 ([Formula: see text] < 0.0001) compared with the DSS group. Analysis of metabolic profiles of serum revealed that treatment groups were clearly separated from the DSS group, suggesting that JGT and acupuncture treatment altered serum metabolites. Furthermore, treatments caused opposite metabolite patterns for dimethylbenzimidazole, 1,5-anhydro-D-glucitol, proline, phosphate, glycolic acid, aspartic acid, tryptophan, phthalic acid, ornithine, and glutamic acid compared with the DSS group. The combined treatment group induced more effective metabolite patterns than the JGT group, implying that acupuncture treatment can restore metabolic changes caused by DSS induction. These results indicate that the simultaneous treatment of JGT administration and acupuncture procedure provides better management of the immune function and inflammatory expression of colitis than a single treatment. It is assumed that intestinal microbial control can be achieved by acupuncture stimulation as well as by taking herbal medicine.