ABSTRACT
Traditional Korean medicine (TKM) emphasizes individualized diagnosis and treatment. This uniqueness makes AI modeling difficult due to limited data and implicit processes. Large language models (LLMs) have demonstrated impressive medical inference, even without advanced training in medical texts. This study assessed the capabilities of GPT-4 in TKM, using the Korean National Licensing Examination for Korean Medicine Doctors (K-NLEKMD) as a benchmark. The K-NLEKMD, administered by a national organization, encompasses 12 major subjects in TKM. GPT-4 answered 340 questions from the 2022 K-NLEKMD. We optimized prompts with Chinese-term annotation, English translation for questions and instruction, exam-optimized instruction, and self-consistency. GPT-4 with optimized prompts achieved 66.18% accuracy, surpassing both the examination's average pass mark of 60% and the 40% minimum for each subject. The gradual introduction of language-related prompts and prompting techniques enhanced the accuracy from 51.82% to its maximum accuracy. GPT-4 showed low accuracy in subjects including public health & medicine-related law, internal medicine (2), and acupuncture medicine which are highly localized in Korea and TKM. The model's accuracy was lower for questions requiring TKM-specialized knowledge than those that did not. It exhibited higher accuracy in diagnosis-based and recall-based questions than in intervention-based questions. A significant positive correlation was observed between the consistency and accuracy of GPT-4's responses. This study unveils both the potential and challenges of applying LLMs to TKM. These findings underline the potential of LLMs like GPT-4 in culturally adapted medicine, especially TKM, for tasks such as clinical assistance, medical education, and research. But they also point towards the necessity for the development of methods to mitigate cultural bias inherent in large language models and validate their efficacy in real-world clinical settings.
ABSTRACT
BACKGROUND: Rikkunshito has been used to treat gastrointestinal (GI) disorders. The purpose of this study was to investigate the effects of Rikkunshito, a traditional Japanese herbal medicine, on the pacemaker potentials of interstitial cells of Cajal (ICCs) from the small intestines of mice. METHODS: We isolated ICCs from the small intestines of mice, and the whole-cell patch-clamp configuration was used to record the pacemaker potentials in cultured ICCs and membrane currents. RESULTS: Rikkunshito depolarized ICC pacemaker potentials in a dose-dependent manner. Pretreatment with GSK1614343 or (D-Lys3)-growth hormone-releasing peptide-6 inhibited Rikkunshito-induced depolarization of pacemaker potentials. Intracellular GDP-ß-S inhibited Rikkunshito-induced effects. In Ca2+-free solution or in the presence of thapsigargin, Rikkunshito did not depolarize pacemaker potentials. Moreover, in the presence of U-73122 or xestospongin C, Rikkunshito-induced effects were inhibited. However, in the presence of staurosporine, Go6976 or Rottlerin, Rikkunshito depolarized pacemaker potentials. Furthermore, Rikkunshito inhibited both transient receptor potentials melastatin 7 (TRPM7) and Ca2+-activated Cl- channels (ANO1) currents. CONCLUSION: Rikkunshito depolarized pacemaker potentials of ICCs via ghrelin receptor and G protein through internal or external Ca2+-, phospholipase C-, and inositol triphosphate-dependent and protein kinase C-, TRPM7-, and ANO1-independent pathways. The study shows that Rikkunshito may alleviate GI motility disorders through its depolarizing effects on ICCs.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Gastrointestinal Motility/drug effects , Interstitial Cells of Cajal/drug effects , Membrane Potentials/drug effects , Receptors, Ghrelin/metabolism , Animals , Cells, Cultured , Dose-Response Relationship, Drug , Gastrointestinal Motility/physiology , Interstitial Cells of Cajal/physiology , Intestine, Small/cytology , Intestine, Small/physiology , Mice , Patch-Clamp Techniques , Primary Cell Culture , Signal Transduction/drug effectsABSTRACT
BACKGROUND: The traditional medicine (TRM) of Korea and China share the same cultural tradition for thousands of years, and has experienced modernization process with respect to their distinctive social, cultural, and political influences. The purpose of this study was to analyze the attitude of Korean and Chinese TRM doctors on the current situation and future perspectives of the TRM education. METHODS: We analyzed the recognition on the current educational system, and needed curriculums from Korean (n = 188) and Chinese (n = 118) TRM doctors. The validity of the structured questionnaire was examined with exploratory factor analysis with varimax rotation and reliability with Cronbach α. The differences between Korean and Chinese TRM doctors were examined with t test. RESULTS: Chinese TRM doctors consider their educational system more positively as for the standardization and professional ethics than the Korean. The Korean and Chinese wanted more emphasis on the education of medical humanities, clinical skills, medical classics, and alternative medicine, although it was more prominent with the Chinese. CONCLUSION: This study revealed the attitude of Korean and Chinese TRM doctors on their educational system, and discussed the implication of similarities and differences between them. It would provide foundations for the improvement of the TRM educational curriculums.
ABSTRACT
Korea has kept the heritage of Korean traditional medicine (KM) during the 19th century harsh modernization, and has established a medical system in parallel with Western medicine. The purpose of this study was to review systematically the history and current system for educating highly qualified traditional medical doctors in Korea. KM produces 750 certified medical doctors every year with a 4-7-year curriculum in 12 universities and their affiliated hospitals. There are 22,074 clinicians along with 2474 clinical specialists in eight departments as of 2014. A national licensing examination and continuing medical education for KM are used for maintaining qualifications of KM doctors, and independent organizations are established for the evaluation of educational institutes. KM has thrived to establish an independent and competitive educational system for KM doctors, equivalent to Western medicine, and has regained a pivotal role for public health in Korea. This study would be useful for cultivating traditional medicine and establishing its educational system in the world.
ABSTRACT
The interstitial cells of Cajal (ICCs) are the pacemaker cells in the gastrointestinal (GI) tract. In the present study, the effects of Dangkwisoosan (DS) on pacemaker potentials in cultured ICCs from the small intestine of the mouse were investigated. The wholecell patchclamp configuration was used to record pacemaker potentials from cultured ICCs and the increase in intracellular Ca2+ concentration ([Ca2+i) was analyzed in cultured ICCs using fura2acetoxymethyl ester. The generation of pacemaker potentials in the ICCs was observed. DS produced pacemaker depolarizations in a concentration dependent manner in current clamp mode. The 4diphenylacetoxyNmethylpiperidine methiodide muscarinic M3 receptor antagonist inhibited DSinduced pacemaker depolarizations, whereas methoctramine, a muscarinic M2 receptor antagonist, did not. When guanosine 5'[ßthio] diphosphate (GDPßS; 1 mM) was in the pipette solution, DS marginally induced pacemaker depolarizations, whereas low Na+ solution externally eliminated the generation of pacemaker potentials and inhibited the DSinduced pacemaker depolarizations. Additionally, the nonselective cation channel blocker, flufenamic acid, inhibited the DSinduced pacemaker depolarizations. Pretreatment with Ca2+free solution and thapsigargin, a Ca2+ATPase inhibitor in the endoplasmic reticulum, also eliminated the generation of pacemaker currents and suppressed the DSinduced pacemaker depolarizations. In addition, [Ca2+]i analysis revealed that DS increased [Ca2+]i. These results suggested that DS modulates pacemaker potentials through muscarinic M3 receptor activation in ICCs by G proteindependent external and internal Ca2+ regulation and external Na+. Therefore, DS were observed to affect intestinal motility through ICCs.
Subject(s)
Interstitial Cells of Cajal/drug effects , Pain/drug therapy , Phytotherapy , Animals , Calcium-Transporting ATPases/antagonists & inhibitors , Calcium-Transporting ATPases/metabolism , Cells, Cultured , Diamines/pharmacology , Female , Gastrointestinal Motility/drug effects , Guanosine Diphosphate/analogs & derivatives , Guanosine Diphosphate/metabolism , Intestine, Small/cytology , Intestine, Small/drug effects , Male , Mice , Mice, Inbred BALB C , Piperidines/pharmacology , Plants, Medicinal/adverse effects , Receptor, Muscarinic M2/antagonists & inhibitors , Receptor, Muscarinic M2/metabolism , Receptor, Muscarinic M3/antagonists & inhibitors , Receptor, Muscarinic M3/metabolism , Thapsigargin/pharmacology , Thionucleotides/metabolismABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Ge-Gen-Tang (GGT) is a traditional Chinese medicinal formula composed of Puerariae radix (Pueraria lobata Ohwi), Ephedrae Herba (Ephedra sinica Stapf), Cinnamomi Ramulus (Cinnamomum cassia Blume), Paeoniae Radix (Paeonia lactiflora Pallas), Glycyrrhizae Radix preparata (Glycyrrhiza uralensis Fischer), Zingiberis Rhizoma (Zingiber officinale Roscoe), and Zizyphi Fructus (Ziziphus jujuba Mill. var. inermis Rehder) and is widely used to ameoliorate the symptoms of gastrointestinal (GI) disorders related to diarrhea and intestinal mucosal immunity and for anti-cold, antipyretic and analgesic in Eastern Asia. AIM OF THE STUDY: Interstitial cells of Cajal (ICCs) are pacemaker cells in the GI tract that generate rhythmic oscillations in membrane potentials known as slow waves. We investigated the effects of GGT on pacemaker potentials in cultured ICCs from the mouse small intestine, and sought to identify the receptors and the action mechanisms involved. MATERIALS AND METHODS: Enzymatic digestions were used to dissociate ICCs from mouse small intestine tissues. All experiments on ICCs were performed on within 12h after culture. A whole-cell patch-clamp configuration was used to record potentials (current clamp) from cultured ICCs. Intracellular Ca(2+) ([Ca(2+)]i) increase was studied in cultured ICCs using fura-2AM. All of the experiments were performed at 30-32°C. RESULTS: Under the current clamping mode, GGT decreased the amplitude and frequency of pacemaker potentials; however, these effects were blocked by intracellular GDPßS, a G-protein inhibitor, and glibenclamide, a specific ATP-sensitive K(+) channels blocker. Prazosin (α1-adrenoceptor antagonist) and butoxamine (ß2-adrenoceptor antagonist) did not block the GGT-induced effects, whereas atenolol (ß1-adrenoceptor antagonist) blocked the GGT-induced effects. Also, yohimbine (α2-adrenoceptor antagonist) partially blocked the GGT-induced effects. Pretreatment with SQ-22536, an adenylate cyclase inhibitor, did not block the GGT-induced effects, whereas pretreatment with ODQ, a guanylate cyclase inhibitor, or L-NAME, an inhibitor of nitric oxide (NO) synthase, did. Additionally, [Ca(2+)]i analysis showed that GGT decreased [Ca(2+)]i. CONCLUSION: These results suggest that GGT inhibits pacemaker potentials in ICCs in a G protein-, cGMP- and NO-dependent manner through stimulation of α2 and ß1-adrenoceptors.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Interstitial Cells of Cajal/drug effects , KATP Channels/metabolism , Membrane Potentials/drug effects , Animals , Cells, Cultured , Cyclic GMP/metabolism , Female , Interstitial Cells of Cajal/metabolism , Intestine, Small/cytology , Intestine, Small/drug effects , Intestine, Small/metabolism , Male , Mice , Mice, Inbred BALB C , Nitric Oxide/metabolism , Patch-Clamp Techniques , Receptors, Adrenergic, alpha-2/drug effects , Receptors, Adrenergic, alpha-2/metabolism , Receptors, Adrenergic, beta-1/drug effects , Receptors, Adrenergic, beta-1/metabolismABSTRACT
AIM: To investigate the effects of Lizhong Tang, an herbal product used in traditional Chinese medicine, on mouse small intestine interstitial cells of Cajal (ICCs). METHODS: Enzymatic digestions were used to dissociate ICCs from mouse small intestine tissues. The ICCs were morphologically distinct from other cell types in culture and were identified using phase contrast microscopy after verification with anti c-kit antibody. A whole-cell patch-clamp configuration was used to record potentials (current clamp) from cultured ICCs. All of the experiments were performed at 30-32â °C. RESULTS: ICCs generated pacemaker potentials, and Lizhong Tang produced membrane depolarization in current-clamp mode. The application of flufenamic acid (a nonselective cation channel blocker) abolished the generation of pacemaker potentials by Lizhong Tang. Pretreatment with thapsigargin (a Ca²âº-ATPase inhibitor in the endoplasmic reticulum) also abolished the generation of pacemaker potentials by Lizhong Tang. However, pacemaker potentials were completely abolished in the presence of an external Ca²âº-free solution, and under this condition, Lizhong Tang induced membrane depolarizations. Furthermore, When GDP-ß-S (1 mmol/L) was in the pipette solution, Lizhong Tang still induced membrane depolarizations. In addition, membrane depolarizations were not inhibited by chelerythrine or calphostin C, which are protein kinase C inhibitors, but were inhibited by U-73122, an active phospholipase C inhibitors. CONCLUSION: These results suggest that Lizhong Tang might affect gastrointestinal motility by modulating pacemaker activity in interstitial cells of Cajal.
Subject(s)
Biological Clocks/drug effects , Drugs, Chinese Herbal/pharmacology , Interstitial Cells of Cajal/drug effects , Intestine, Small/drug effects , Animals , Biomarkers/metabolism , Cells, Cultured , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Female , Gastrointestinal Motility/drug effects , Interstitial Cells of Cajal/metabolism , Intestine, Small/metabolism , Ion Channels/antagonists & inhibitors , Ion Channels/metabolism , Male , Membrane Potentials/drug effects , Membrane Transport Modulators/pharmacology , Mice , Mice, Inbred BALB C , Proto-Oncogene Proteins c-kit/metabolism , Sarcoplasmic Reticulum Calcium-Transporting ATPases/antagonists & inhibitors , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism , Signal Transduction/drug effectsABSTRACT
OBJECTIVE: Pyungwi-san (PWS) plays a role in a number of physiologic and pharmacologic functions in many organs. Interstitial cells of Cajal (ICCs) are pacemaker cells that generate slow waves in the gastrointestinal (GI) tract. We aimed to investigate the beneficial effects of PWS in mouse small-intestinal ICCs. METHODS: Enzymatic digestion was used to dissociate ICCs from the small intestine of a mouse. The wholecell patch-clamp configuration was used to record membrane potentials from the cultured ICCs. RESULTS: ICCs generated pacemaker potentials in the GI tract. PWS produced membrane depolarization in the current clamp mode. Pretreatment with a Ca(2+) -free solution and a thapsigargin, a Ca(2+) -ATPase, inhibitor in the endoplasmic reticulum, eliminated the generation of pacemaker potentials. However, only when the thapsigargin was applied in a bath solution, the membrane depolarization was not produced by PWS. Furthermore, the membrane depolarizations due to PWS were inhibited not by U-73122, an active phospholipase C inhibitor, but by chelerythrine and calphostin C, protein kinase C inhibitors. CONCLUSIONS: These results suggest that PWS might affect GI motility by modulating the pacemaker activity in the ICCs.
ABSTRACT
A systematic review of studies related to the psychological characteristics of Sasang types was conducted with the goal of delineating generalizable psychological profiles based on Sasang typology, a traditional Korean medical typology with medical herbs and acupuncture that is characterized as personalized medicine. Journal articles pertaining to Sasang typology were collected using five electronic database systems in Korea and in the USA. As a result, 64 potentially relevant studies were identified and 21 peer-reviewed research articles that employed psychometric inventories were included. Beginning with the use of the Minnesota Multiphasic Personality Inventory in 1992, Myers-Briggs Type Indicator, NEO-Personality Inventory, Temperament and Character Inventory and other personality assessment tools were employed in the identified studies. Because data synthesis could not be carried out due to the heterogeneity of the studies, the present review article sought to delineate the mutual relevance of the studies based on research results pertaining to the correlation between the aforementioned psychological assessment instruments. Results of the review indicate that two super-factors, Extraversion and Neuroticism, serve as the foundation in regards to delineating personality constructs, such that the So-Yang type scored high on the Extraversion dimension and low on the Neuroticism dimension, while the So-Eum type scored low on the Extraversion dimension and high on the Neuroticism dimension. The present systematic review indicates that Sasang typology shares similarities with the Western psychological tradition.
ABSTRACT
The purpose of this study was to examine the relationship between variations in skin humidity (SH) induced by perspiration across Sasang types and to identify novel and effective Sasang classification factors. We also analyzed the responses of each Sasang type to sweating-related QSCC II items. The results revealed a significant difference in SH across gender and significant differences in SH before and after perspiration between Tae-Eum and So-Eum men. In addition, Tae-Eum women showed significant differences in SH compared with women classified as another Sasang type. Furthermore, evaluation of the items related to sweating in the QSCC II and their relationship to each constitution revealed a significant difference between Tae-Eum and other Sasang types. Overall, the results of this study indicate that there is a distinct SH difference following perspiration between Tae-Eum and other Sasang types. Such findings may aid in Sasang typology diagnostic testing with the support of further sophisticated clinical studies.
ABSTRACT
Licorice is commonly used as a cure for digestive disorders and as a detoxification agent in East Asia. This study investigated the protective effect of licorice water extract against cadmium (CdCl(2), Cd)-induced liver toxicity in rats. To induce acute toxicity, Cd (4 mg/kg body weight) was dissolved in normal saline and intravenously (i.v.) injected into rats. The rats then received either a vehicle or licorice water extract (50, 100 mg/kg/day) for 3 days, and were subsequently exposed to a single injection of Cd 24 h after the last licorice/vehicle treatment. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were significantly increased by Cd treatment. In contrast, pretreatment with licorice reduced ALT, AST and LDH. In histopathological analysis, licorice decreased the central necrosis around central veins, the peripheral hemorrhage around portal triads, the percentage of degenerative hepatic regions (%/mm(2) hepatic parenchyma) and the number of degenerative hepatic cells (N/100 hepatic cells). Licorice also inhibited the increment of Bad (a BH3 domain-containing protein) translocation by Cd in liver cells. These results demonstrate that licorice could have a hepatoprotective effect by inhibiting the translocation of Bad to the mitochondria in Cd-intoxificated rats.
ABSTRACT
In our previous study we demonstrated that acupuncture at Shenmen (HT7) points suppressed a decrease of accumbal dopamine (DA) release in ethanol-withdrawn rats. Furthermore, here we found that it inhibited behavioral withdrawal signs of ethanol. In an effort to better understand the mechanisms underlying this inhibition, the potential role of GABA receptor system in acupuncture was investigated. Male Sprague-Dawley rats were treated with 3g/kg/day of ethanol (20%, w/v) or saline by intraperitoneal injection for 21 days. Following 48 or 72h of ethanol withdrawal, acupuncture was applied at bilateral HT7 for 1min. The selective GABA(A) antagonist bicuculline and the selective GABA(B) antagonist SCH 50911 were injected intraperitoneally 20min before acupuncture, respectively. Importantly, suppressive effects of acupuncture on DA deficiency were completely abolished by SCH 50911, but not by bicuculline, whereas ameliorating effects of acupuncture on ethanol withdrawal syndrome were completely blocked either by SCH 50911 or bicuculline. These results suggest that acupuncture at specific acupoint HT7 may normalize the DA release in the mesolimbic system and attenuate withdrawal syndrome through the GABA(B) receptor system in ethanol-withdrawn rats.
Subject(s)
Acupuncture/methods , Behavior, Animal/physiology , Brain Chemistry/physiology , Ethanol/adverse effects , Substance Withdrawal Syndrome/etiology , Substance Withdrawal Syndrome/rehabilitation , Acupuncture Points , Analysis of Variance , Animals , Behavior, Animal/drug effects , Bicuculline/pharmacology , Disease Models, Animal , Dopamine/metabolism , GABA Agents/pharmacology , Male , Morpholines/pharmacology , Motor Activity/drug effects , Motor Activity/physiology , Motor Activity/radiation effects , Rats , Rats, Sprague-Dawley , Time Factors , gamma-Aminobutyric Acid/metabolismABSTRACT
AIM OF THE STUDY: The anti-osteoporotic effect of heated powder of Ostreae Testa (hPOT), a powder of oyster shell-Ostrea gigas Thumb (Ostrediae) was observed in vitro and in vivo. MATERIALS AND METHODS: The effects on proliferation and alkaline phosphatase activity of primary osteoblasts, bone nodule formation, pit formation of osteoclasts and osteoclastogenesis were observed in vitro, and to observe the in vivo efficacy hPOT was orally administered once a day for 28 days to bilateral ovariectomy-induced osteoporosis mice at 125, 250 and 500mg/kg (of body weight). RESULTS: Although hPOT did not influence the pit formation and the number of multinucleated osteoclast-like cells, osteoclastogenesis, it enhanced the proliferation of primary osteoblasts, differentiation (ALP activity) and bone nodule formation of osteoblast in vitro. The estrogen-deficient osteoporotic changes were dramatically prevented by hPOT treatment except for osteoclasts/bone perimeter. CONCLUSIONS: In conclusion, hPOT prevents OVX-induced osteoporosis through osteoblasts activation effects.
Subject(s)
Medicine, Chinese Traditional , Osteoblasts/drug effects , Osteoporosis/prevention & control , Ostrea , Ovariectomy/adverse effects , Alkaline Phosphatase/metabolism , Animals , Bone Density/drug effects , Bone and Bones/drug effects , Bone and Bones/pathology , Mice , Mice, Inbred ICR , Osteoblasts/physiology , PowdersABSTRACT
Many studies have shown that acupuncture can contribute to the biochemical balance in the central nervous system and maintenance or recovery of homeostasis. It is well known that chronic administration of ethanol may produce depletion or sensitization of extracellular dopamine levels in the nucleus accumbens. The present study was designed to investigate the effects of acupuncture on chronic ethanol-induced changes in extracellular dopamine levels in the nucleus accumbens shell (using in vivo microdialysis in unanesthetized rats). Male Sprague-Dawley rats were treated with 3 g/kg/day of ethanol (20%, w/v) or saline by intraperitoneal injection for 21 days. Following 72 h of ethanol withdrawal, acupuncture was applied at bilateral Shenmen (HT7) points for 1 min. Different group of rats using the same paradigm of ethanol treatment were acupunctured at the same points after the systemic ethanol challenge (3 g/kg, i.p.). Acupuncture at the specific acupoint HT7, but not at control points (PC6 or tail) significantly prevented both a decrease of extracellular dopamine levels in the nucleus accumbens during ethanol withdrawal and an increase in accumbal dopamine levels induced by the ethanol challenge. These results provided strong evidence that stimulation of the specific acupoint HT7 helps to normalize the release of dopamine in the mesolimbic system following chronic ethanol treatment.
Subject(s)
Acupuncture Therapy/methods , Alcoholism/metabolism , Dopamine/metabolism , Ethanol/adverse effects , Nucleus Accumbens/metabolism , Substance Withdrawal Syndrome/metabolism , Substance Withdrawal Syndrome/therapy , Alcoholism/therapy , Animals , Chronic Disease , Homeostasis/drug effects , Male , Nucleus Accumbens/drug effects , Rats , Rats, Sprague-Dawley , Treatment OutcomeABSTRACT
Acupuncture as a therapeutic intervention is widely practiced in the treatment of many functional disorders including alcohol abuse. In the present study, the effects of acupuncture on alcohol withdrawal syndrome (AWS) and Fos-like immunoreactivity (FLI) in the striatum and the nucleus accumbens (NAC) of rats were investigated. During 3 days of cessation following chronic administration of ethanol (3 g/kg, i.p. for 3 weeks), rats showed a significant increase in AWS, such as hypermotility, tail rigidity, grooming and tremor, and an increase in FLI in the dopamine terminal areas of the brain. Treatment with acupuncture at zusanli (ST36) or sanyinjiao (SP6) during the withdrawal period inhibited both AWS and FLI of rats undergoing ethanol injection. These results suggest that acupuncture may be useful in the treatment of alcoholism by modulating post-synaptic neural activation in the striatum and NAC.
Subject(s)
Acupuncture Therapy , Brain/metabolism , Central Nervous System Depressants/adverse effects , Ethanol/adverse effects , Proto-Oncogene Proteins c-fos/metabolism , Substance Withdrawal Syndrome/therapy , Acupuncture Points , Animals , Behavior, Animal , Immunohistochemistry , Male , Rats , Rats, WistarABSTRACT
Behavioral sensitization, as evidenced by the progressive enhanced locomotor response to a subsequent injection of the drug, is the major behavioral outcome produced by repeated injections of nicotine, and a model for studying drug addiction. It is putatively regarded that the alteration of extracellular dopamine release in the nucleus accumbens is closely associated with nicotine-induced behavioral sensitization. The present study was performed to evaluate the effects of the essential oil from Angelica gigas NAKAI (on fragrance inhalation) on repeated nicotine-induced locomotor activity and extracellular dopamine levels in the nucleus accumbens of rats using in vivo microdialysis. Rats were given repeated injections of saline or nicotine (0.4 mg/kg s.c., twice a day for 7 d), followed by one challenge injection on the 4th day after the last daily injection. Systemic challenge with nicotine (0.4 mg/kg s.c.) produced a larger increase in locomotor activity in nicotine-pretreated rats than in saline-pretreated rats. A direct local challenge of 3 mM nicotine via a microdialysis probe also induced a larger increase in dopamine release in nicotine-pretreated rats than in saline-pretreated rats. Most importantly, our results showed that inhalation of the essential oils from Angelica gigas NAKAI significantly decreased both dopamine release in the nucleus accumbens and locomotor activity induced by a nicotine challenge. These results suggest that the essential oils from Angelica gigas NAKAI inhibit nicotine-induced behavioral and neurochemical sensitization, and imply that the essential oil from Angelica gigas NAKAI may be effective in treating nicotine addiction, possibly by modulating dopamine release in the nucleus accumbens.
Subject(s)
Angelica , Nicotine/adverse effects , Oils, Volatile/pharmacology , Tobacco Use Disorder/prevention & control , Administration, Inhalation , Animals , Aromatherapy/methods , Dopamine/chemistry , Dopamine/metabolism , Drug Administration Schedule , Injections, Subcutaneous , Male , Mentha/chemistry , Motor Activity/drug effects , Nicotine/administration & dosage , Nucleus Accumbens/chemistry , Nucleus Accumbens/drug effects , Nucleus Accumbens/metabolism , Oils, Volatile/administration & dosage , Plant Leaves/chemistry , Plant Roots/chemistry , Plant Stems/chemistry , Rats , Rats, Sprague-Dawley , Tobacco Use Disorder/physiopathologyABSTRACT
Clinical trials are currently underway to determine the effectiveness of acupuncture in the treatment of drug abuse. However, there are still many unanswered questions about the basic mechanisms of acupuncture. Studies have shown that the GABA(B) receptor system may play a significant modulatory role in the mesolimbic system in drug abuse, including ethanol. The in vivo microdialysis study was designed to investigate the effect of acupuncture on acute ethanol-induced dopamine release in the nucleus accumbens and the potential role of the GABA(B) receptor system in acupuncture. Male Sprague-Dawley rats were administered with the highly selective GABA(B) antagonist SCH 50911 (3 mg/kg, i.p.) 1h prior to an intraperitoneal injection of ethanol (1 g/kg). Immediately after ethanol treatment, acupuncture was given at bilateral Shenmen (HT7) points for 1min. Acupuncture at the specific acupoint HT7, but not at control points (PC6 or tail) significantly decreased dopamine release in the nucleus accumbens. Inhibition of dopamine release by acupuncture was completely prevented by SCH 50911. These results suggest that stimulation of specific acupoints inhibits ethanol-induced dopamine release by modulating GABA(B) activity and imply that acupuncture may be effective in blocking the reinforcing effects of ethanol.
Subject(s)
Acupuncture , Central Nervous System Depressants/pharmacology , Dopamine/metabolism , Ethanol/pharmacology , Nucleus Accumbens/drug effects , Receptors, GABA-B/physiology , Acupuncture Points , Animals , GABA-B Receptor Antagonists , Male , Morpholines/pharmacology , Neural Inhibition/drug effects , Neural Inhibition/radiation effects , Nucleus Accumbens/metabolism , Nucleus Accumbens/radiation effects , Rats , Rats, Sprague-DawleyABSTRACT
Repeated injections of nicotine can produce behavioral sensitization, as evidenced by an enhanced locomotor response to a subsequent injection of the drug. Behavioral sensitization has been suggested as a model for studying drug addiction. Acupuncture as a therapeutic intervention is widely used for treatment for many functional disorders, such as substance abuse and mental dysfunction. We examined the effect of acupuncture on nicotine-induced behavioral locomotor activity and c-fos expression in the nucleus accumbens and striatum utilizing the immunocytochemical detection of the Fos protein. The rats were given repeated daily nicotine injections (0.4 mg/kg s.c., twice daily for 7 days) followed by one challenging injection on the 4th day after the last daily injection. Acupuncture at zusanli (ST36), but not control, significantly attenuated expected increase in nicotine-induced locomotor activity and Fos-like-immunoreactivity in the nucleus accumebns and striatum to subsequent nicotine challenge. These findings suggest that acupuncture has a therapeutic effect on nicotine addiction, possibly by modulating postsynaptic neuronal activity in the nucleus accumbens and the striatum.