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In the present study, the effects of acupuncture on the behavioral and physiological responses induced by chronic mild stress (CMS) were evaluated. Sprague-Dawley rats were exposed to a variety of chronic unpredictable, mild stressors for 8 weeks. The effects of acupuncture on stress-induced anxiety and anhedonia were investigated using the elevated plus maze (EPM) and sucrose intake test. In addition, c-fos expression, as an early neuronal marker in the brain was also examined utilizing Fos-like immunohistochemistry (FLI). CMS rats significantly reduced the consumption of sucrose intake and latency in the open arms of the EPM, and gained body weight more slowly, compared to non-stressed normal rats. Exposure to CMS also significantly increased FLI in the paraventricular nucleus (PVN) of the hypothalamus. Acupuncture stimulation at point PC6 on the pericardium channels (3 min), but not at other point (TE5), restored stress-induced decrease in the latency in the open arms and significantly attenuated FLI in the PVN produced by CMS. Acupuncture stimulation also tended to restore stress-induced decrease in the sucrose intake. The present results demonstrated that acupuncture was effective in restoring CMS-related biochemical and behavioral impairments such as anxiety and anhedonia and that acupuncture point was more effective than non-acupuncture point. These results suggest that acupuncture has a therapeutic effect on chronic stress-related diseases such as depression and anxiety.

Acupuncture is widely used for the treatment of many functional disorders, such as substance abuse, and has the suppressive effect on the central nervous system. Many studies have suggested that behavioral sensitization by repeated injections of cocaine produce an increase in locomotor activity and an increase in the expression of tyrosine hydroxylase (TH), in the central dopaminergic system. In order to investigate the effects of acupuncture on the repeated cocaine-induced neuronal and behavioral sensitization alternations, we examined the influence of acupuncture on the repeated cocaine-induced locomotor activity and the expression of TH in the brain using immunohistochemistry. Male SD rats were given repeated injections of cocaine hydrochloride (15 mg/kg, i.p. for 10 consecutive days) followed by one challenge injection on the 4th day after the last daily injection. Cocaine challenge produced a large increase in the locomotor activity and the expression of TH in the ventral tegmental area (VTA). Treatment with acupuncture bilaterally at the Shenman (HT7) points for 1 min significantly inhibited the increase of locomotor activity as well as the TH expression in the VTA. Our data demonstrated that the inhibitory effects of acupuncture on cocaine-induced expression of behavioral sensitization were closely associated with the reduction of dopamine (DA) biosynthesis and the postsynaptic neuronal activity. These results provide evidence that acupuncture may be effective for inhibiting the behavioral effects of cocaine by possible modulation of the central dopaminergic system.

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.

Acupuncture, likely the most well-known 'alternative' medical treatment, has been shown to have effects in several types of animal model of drug dependence, including nicotine addiction. We investigated the effect of acupuncture on anxiety-like behavior and corticotrophin-releasing factor (CRF) and neuropeptide Y (NPY) mRNA expression in the amygdala during nicotine withdrawal. Rats were given repeated nicotine injections (0.1mg/kg s.c., once daily for 7 days) or saline. Acupuncture groups were treated with acupuncture at acupoint HT7 or ST36 during withdrawal. The anxiogenic response was measured at 72h after the termination of nicotine injection using an elevated plus maze. CRF and NPY mRNA levels were also evaluated using reverse transcription polymerase chain reaction (RT-PCR) analysis at this time. Rats undergoing nicotine withdrawal (NW) were less likely to explore the open arms of the plus maze compared with the saline-treated controls. The percentage of open arm entries in the HT7 acupuncture group, but not in the ST36 acupuncture group, was significantly increased compared with the NW group. Consistent with this behavior, CRF mRNA levels in the NW group were increased compared with the control group. CRF mRNA levels in the HT7 acupuncture group were significantly decreased compared with the NW group. However, NPY mRNA levels were not different among the groups. These findings indicate that increases in CRF may be involved in the negative affect state associated with nicotine withdrawal and that acupuncture may attenuate anxiety-like behavior following nicotine withdrawal by modulating CRF in the amygdala.

Acupoints on the Large Intestine Meridian and specific acupoints related with large intestine have been empirically used to treat large intestinal disease. However, the relationship between acupoints related with large intestine and their functions has not been investigated fully. We investigated whether large intestine-related acupoints affect colonic motility in conscious dogs implanted with electrodes at the proximal colon. Manual acupuncture was applied at the following acupoints: 7 main points on the Large Intestine Meridian (LI1, LI2, LI3, LI4, LI5, LI6, and LI11), ST25, BL25 or GV1. Acupuncture at the Large Intestine Meridian acupoints, ST25 and BL25 had no significant effects on the proximal colonic motility. However, acupuncture at GV1 depressed the proximal colonic motility by decreasing the total duration and the frequency of contractile states, which may contribute to the therapeutic effects of GV1. This study also revealed that there was no clear correlation between Large Intestine Meridian and the proximal colonic motility in conscious dogs.

Acupuncture as a therapeutic intervention has been used for the treatment of many functional disorders including substance abuse. However, there are still many unanswered question about the basic mechanism underlying acupuncture's effectiveness in the treatment of drug addiction. Repeated injection of psycostimulants or morphine can produce behavioral and neurochemical sensitization and have been used as a model for studying drug addiction. The present study was designed to investigate the effect of acupuncture on repeated morphine-induced changes in extracellular dopamine levels using in vivo microdialysis and repeated morphine-induced behavioral changes. Male Sprague-Dawley rats were treated with saline or increasing doses of morphine (10, 20 and 40 mg/kg, s.c., twice daily for 3 days). Following 15 days of withdrawal, acupuncture was applied at bilateral Shenmen (HT7) points for 1 min after the systemic challenge with morphine HCl (5 mg/kg, s.c.). Results showed that acupuncture at the specific acupoint HT7, but not at control points (TE8 and tail) significantly decreased both dopamine release in the nucleus accumbens and behavioral hyperactivity induced by a systemic morphine challenge. These results suggest that the therapeutic effect of acupuncture on morphine addiction occurs through inhibition of neurochemical and behavioral sensitization to morphine.

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.

Parkinson's disease (PD) is caused by the selective loss of dopaminergic neurons in the substantia nigra (SN) and the depletion of striatal dopamine (DA). Acupuncture, as an alternative therapy for PD, has beneficial effects in both PD patients and PD animal models, although the underlying mechanisms therein remain uncertain. The present study investigated whether acupuncture treatment affected dopamine neurotransmission in a PD mouse model using 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP). We found that acupuncture treatment at acupoint GB34 improved motor function with accompanying dopaminergic neuron protection against MPTP but did not restore striatal dopamine depletion. Instead, acupuncture treatment increased dopamine release that in turn, may lead to the enhancement of dopamine availability in the synaptic cleft. Moreover, acupuncture treatment mitigated MPTP-induced abnormal postsynaptic changes, suggesting that acupuncture treatment may increase postsynaptic dopamine neurotransmission and facilitate the normalization of basal ganglia activity. These results suggest that the acupuncture-induced enhancement of synaptic dopamine availability may play a critical role in motor function improvement against MPTP. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the effect of acupuncture to the acupuncture point HT7 (Sinmun) on morphine-induced behavioral sensitization and the neuronal changes in nucleus accumbens and striatum in rats. Methods: Male Sprague–Dawley rats were given repeated injections of morphine hydrochloride for 5 days followed by 3 day withdrawal and one challenge injection. The acupuncture treatment was performed for 1 minute once a day for 3 days of withdrawal period and its effect on morphine-induced changes of locomotor activity and Fos expression was examined. Results: The acupuncture stimulation to HT7 significantly suppressed the morphine-induced increases in the locomotor activity and Fos expression in the nucleus accumbens and striatum, as compared to the controls of non-acupoint or the acupoint on other meridian. Discussion: These results demonstrated that the inhibitory effect of the acupuncture stimulation to HT7 on morphine-induced behavioral sensitization was closely associated with the suppression of dopamine biosynthesis and its activity in the post-synaptic neurons in nucleus accumbens and striatum. It means that the behavioral effect of the acupuncture can originate from the modulation of the same neuronal mechanism in the central dopaminergic system as in the morphine-induced behavioral sensitization. This modulation was also strictly confined to the stimulation of the specific acupoint, because the stimulation to other acupoint (TE5) on another meridian did not show the modulating effect despite being relatively close to each other. It can be therefore suggested that the acupuncture stimulation has an acupoint-specific property, and might be a useful therapeutic alternative with few side effects for treating morphine addiction. [ABSTRACT FROM AUTHOR]

Objectives: In order to apply appropriate acupuncture stimulation, different needle manipulation techniques are required. These manipulations are performed in many ways such as twirling the needle, varying the insertion angle, etc. The present study was designed to evaluate the antinociceptive effect of these manipulations to the acupuncture point ST36 on formalin-induced pain in rats. Methods: Animals were divided into four groups: non-treated control (CON), acupuncture without manipulation (AT), acupuncture with twirling manipulation (TM) and acupuncture with lifting–thrusting manipulation (LM) group. Level of pain was measured in formalin-injected rats in the early (0–10 minutes) and the late (10–60 minutes) phase. Several pain-related gene expressions were investigated in the spinal cord using reverse transcriptase-polymerase chain reaction analysis. Results: Formalin-induced pain was significantly reduced in the TM and the LM groups, compared with the CON and the AT groups. TM was more effective than LM in both phases. Needle manipulation was also effective in suppressing the mRNA expression of pain-related genes such as Fos, opioid receptor-like 1, tachykinin 1, tachykinin receptor 1, μ-opioid receptor and 5-hydroxytryptamine receptor 2A in the spinal cord. Discussion: The TM and the LM groups showed enhanced analgesia, compared with the AT group. This effect might be related to the suppression of the transcription of pain-related genes. [ABSTRACT FROM AUTHOR]

Abstract: Repeated injection of corticosterone (CORT) induces dysregulation in the HPA axis, resulting in depression and anxiety. Many studies have shown that acupuncture, which is widely used for the treatment of stress and mental illness, in East Asian countries, is an effective therapeutic intervention for psychosomatic disorders. We investigated the influence of acupuncture therapy on chronic CORT-induced behavioral responses to the forced swimming test (FST) and elevated plus maze (EPM) and expression of neuropeptide Y (NPY) in the rat brain using immunohistochemistry. Male Sprague-Dawley rats were injected with CORT (40mg/kg, i.p.) once daily for 19 consecutive days. The dysregulation of HPA axis by external injection of CORT was confirmed by measuring the CORT concentration in plasma and the expression level of CRF in hypothalamus. Acupuncture was performed at the PC6 acupoint for 5min before CORT injection. Acupuncture significantly reduced depression- and anxiety-like behavior and increased NPY expression in the hypothalamus. These results demonstrated that stimulation of the PC6 acupoint suppresses the symptopathology of the hypoactivated HPA axis in chronic CORT-induced rat model of depression. [Copyright &y& Elsevier]

Abstract: Warm needle acupuncture (WNA) therapy combines the effects of acupuncture and heat produced by moxibustion. This therapy has been widely used in Korean traditional medicine to treat a number of health problems. We evaluated the analgesic effect of WNA treatment on formalin-induced pain behavior and c-Fos expression in the spinal cord of rats. Acupuncture and heat stimulation by moxibustion were performed at the Pungsi (GB31) acupoint. Needle insertion without heat stimulation (ACU) and heat stimulation without needle insertion (SWNA) were used as negative controls. WNA therapy was executed by burning 1.5g of cylinder-shaped moxa on top of the needle that was inserted at the acupoint. We measured temperatures of two different locations on the needle using an automatic temperature-acquisition system. Needle temperatures were overwhelmingly dependent on the distance from moxa while burning and showed a maximum of 44.9°C at the location 7mm apart from the ground after ignition. WNA treatment was more effective than ACU or SWNA in alleviating pain during the late phase in the rat formalin test. WNA, ACU, and SWNA significantly reduced c-Fos expression in the superficial dorsal horn by 23.5, 28.3 and 19.4%, respectively. [Copyright &y& Elsevier]

The effects of acupuncture and electroacupuncture on an animal model of arthritic pain were examined. Under halothane anesthesia, arthritic pain was induced by the injection of carrageenan into the knee joint cavity of male Sprague-Dawley rats. Behavioral performance was tested before and after the termination of acupuncture or electroacupuncture. Electrophysiologically, the responses of afferents to a movement cycle were recorded before and after acupuncture or electroacupuncture. After the acupuncture procedure, the weight-bearing force of the rats was significantly improved and the neural responses to noxious movement stimulation were reduced. Electroacupuncture significantly improved weight-bearing behavior and inhibited neural responses of articular afferents to noxious stimulation. These results indicate that acupuncture and electroacupuncture may provide a potent strategy in relieving arthritic pain. [ABSTRACT FROM AUTHOR]

Abstract: This study first showed the behavioural benefits of novel combination therapy of l-dopa with acupuncture on Parkinson's disease, and its underlying mechanisms within basal ganglia. The previous study reported that acupuncture may improve the motor function of a Parkinson's disease (PD) mouse model by increasing the dopamine efflux and turnover ratio of dopamine. Hence, we hypothesised that combining l-dopa with acupuncture would have a behavioural benefit for those with PD. We performed unilateral injections of 6-OHDA into the striatum of C57Bl/6 mice to model hemi-Parkinsonian attributes. To test motor function and dyskinetic anomalies, we examined cylinder behaviour and abnormal involuntary movement (AIM), respectively. We found that (1) a 50% reduced dose of l-dopa (7.5mg/kg) combined with acupuncture showed an improvement in motor function that was comparable to mice given the standard dose of l-dopa treatment (15mg/kg) only, and that (2) the combination treatment (l-dopa +acupuncture) was significantly superior in reducing AIM scores when equivalent doses of l-dopa were used. The combination treatment also significantly reduces the abnormal increase of GABA contents in the substantia nigra compared to the standard l-dopa treatment. Furthermore, abnormal expression of FosB, the immediate early gene of l-dopa induced dyskinesia (LID), was mitigated in the striatum by the combination treatment. All of these results indicate that acupuncture enhances the benefits of l-dopa on motor function with reduced dose of l-dopa and alleviating LID by normalising neurochemical imbalance within the basal ganglia. [Copyright &y& Elsevier]

Abstract: A previous study reported that the PC6 acupuncture point can alleviate chronic mild stress (CMS)-induced anxiety . Following the previous study, this study examined the effects of the PC6 acupuncture point on CMS-induced memory loss. The memory storage and acetylcholinesterase (AchE) activity in the hippocampus were measured, respectively, using a passive avoidance test (PAT) and AchE immunohistochemistry. In the PAT (retention test), the CMS group showed a markedly lower latency time than the control (post (72h): P <0.01, post (96h): P <0.05, post (120h): P <0.001). However, acupuncture at PC6 significantly recovered the impairment of memory compared to the CMS group (post (120h): P <0.001). Exposure to CMS also significantly decreased the AchE activity in the hippocampus compared to the control rats. Acupuncture stimulation at the PC6 point on the pericardium channels (3min), but not at other points (TE5), produced memory improvements and an increase in AchE reactivity in the hippocampus compared to the CMS group. These results show that the acupuncture point is effective in restoring the CMS-related biochemical and behavioral impairments, such as learning and memory. [ABSTRACT FROM AUTHOR]

Abstract: To enhance the medicinal activity of bee venom (BV) acupuncture, bee venom was loaded into biodegradable poly(d,l-lactide-co-glycolide) nanoparticles (BV-PLGA-NPs) by a water-in-oil-in-water-emulsion/solvent-evaporation technique. Rat formalin tests were performed after subcutaneous injection of BV-PLGA-NPs to the Zusanli acupuncture point (ST36) at 0.5, 1, 2, 6, 12, 24, and 48h before plantar injection of 2% formalin. BV-PLGA-NPs treatment showed comparable analgesic activity to typical BV acupuncture during the late phase, compared with saline-treated controls, and the analgesic effect lasted for 12h. PLGA-encapsulation was also effective in alleviating the edema induced by allergens in bee venom. These results indicate that PLGA-encapsulation provided a more prolonged effect of BV acupuncture treatment, while maintaining a comparable therapeutic effect. [Copyright &y& Elsevier]

Abstract: 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 3g/kg/day of ethanol (20%, w/v) or saline by intraperitoneal injection for 21 days. Following 72h of ethanol withdrawal, acupuncture was applied at bilateral Shenmen (HT7) points for 1min. Different group of rats using the same paradigm of ethanol treatment were acupunctured at the same points after the systemic ethanol challenge (3g/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. [Copyright &y& Elsevier]

Abstract: Recent studies have suggested that maternally deprived rats exhibit anxiogenic-like behavior when exposed to stress in later life. Neuropeptide Y (NPY) is involved in the regulation of various physiological functions such as the expression of anxiety. Female Wistar rat pups were separated from their mothers for 3h daily from postnatal days 3 (P3) to 14 (P14). Acupuncture groups were treated with acupuncture at Shenmen (HT7) or Zusanli (ST36) on alternate days from P50 to P62. Their anxiety-like behavior was evaluated using an elevated plus-maze at P62, and then NPY immunohistochemistry in the basolateral amygdala (BLA) was performed. Rats exposed to maternal separation (MS) were less likely to explore the open arms of the plus-maze compared to control rats that were not exposed to MS. Among maternally separated groups, the percentage of time spent in the open arms was significantly increased in the HT7 acupuncture group, but not the ST36 acupuncture group, compared to MS group. In accordance with this behavior, the numbers of NPY-immunoreactive cells in the BLA were lower in the MS group compared to the control group. Among maternally separated groups, the numbers of NPY-immunoreactive cells in the BLA were significantly higher in the HT7 acupuncture group, but not higher in the ST36 acupuncture group, compared to MS group. These findings suggest that acupuncture treatment might reduce anxiety-like behavior in adult rats following maternal separation by modulating the NPY system in the amygdala. [Copyright &y& Elsevier]

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 GABAB 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 GABAB receptor system in acupuncture. Male Sprague–Dawley rats were administered with the highly selective GABAB antagonist SCH 50911 (3mg/kg, i.p.) 1h prior to an intraperitoneal injection of ethanol (1g/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 GABAB activity and imply that acupuncture may be effective in blocking the reinforcing effects of ethanol. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]