• Journal of Oriental Neuropsychiatry
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• v.14 no.1
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• pp.27-44
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• 2003

Objective : The aim of this study was to assess protective effects of Whangryonhaedoktang on the chronic mild stress (CMS) animal model of depression. Method : Male Sprague-Dawley rats were used for this study. The subjects were divided into 3 groups (CMS-drug group: Whangryonhaedoktang was administered during CMS procedure, CMS-vehicle: water was administered during CMS procedure, normal control group: without CMS procedure). After 4 weeks of CMS procedure, Morris water maze (MWM) test and open field test were executed and tyrosine hydroxylase (TH) was measured in ventral tegmental area (VTA) and locus coeruleus (LC) of rat brain. Result : 1. CMS procedure induced defects of spatial learning in early period of MWM test. 2. CMS Whangryonhaedoktang group showed shorter escape latency in comparison with CMS control group in MWM test on the first day of the test. 3. CMS Whangryonhaedoktang group and CMS control group showed no significant difference of activities and emotional behaviors in comparison with normal control group in open field test. 4. CMS Whangryonhaedoktang group showed significant inhibition effects of TH expression in VTA and LC areas in comparison with CMS control group. Conclusion : These results suggest that Whangryonhaedoktang may have inhibition effects to early period defects of spatial learning and protective antidepressant effects in CMS model rats.

• The Journal of Internal Korean Medicine
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• v.36 no.4
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• pp.507-517
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• 2015

The bark of Magnolia officinalis has been used in traditional oriental medicine to treat a variety of mental disorders including anxiety and depression. The purpose of this study was to examine the effect of M. officinalis ethanol extract on stress-induced alterations in learning and cognitive function using a passive avoidance test (PAT) and also on anxiety-related behavior using the elevated plus-maze test (EPM) in female rats . The degree of Tyrosine hydroxylase (TH) in the region of the ventral tegmental area (VTA) and the locus coeruleus (LC) was measured using an immunohistochemical method. Corticosterone concentrations in serum were also measured. The ethanol extract from Magnolia officinalis was orally administered to female rats 30 minutes before evaluating their immobilization stress and anxiety-related behavior using an elevated plus-maze test and a passive avoidance test. Time spent in the open arms of the EPM increased in the M. officinalis-treated group compared with that of the saline-treated control group. In the passive avoidance test, the memory and cognitive function improved in the M. officinalis extract-treated group. M. officinalis extracts reduced elevated corticosterone concentrations in serum. Also, stress-induced TH increases were suppressed in the M. officinalis extract-treated group in the LC and the VTA region. These results suggest that M. officinalis might prove to be an effective anxiolytic anti-stress agent.

• The Korean Journal of Pharmacology
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• v.30 no.1
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• pp.29-37
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• 1994

Inhibition of the nociceptive Tail Flick Reflex (TFR) was observed with electrical stimulation of the locus coeruleus/subcoeruleus (LC/SC) in the male Sprague - Dawley rats under light anesthesia, and the involved neurotransmitter (s) were characterized. Electrical stimulation of LC/SC induced the analgesia with the stimulation threshold (intensity of the current, given for 100 usec and in 100 Hz frequency, which caused the TF latency longer than 6.5 sec) around 55 uA. Intrathecal administrations of ${\alpha}_2$ antagonist, yohimbine (30 ug) or opioid antagonist, naloxone (20 ug) increased the stimulation threshold by 147% and 123% respectively (from 55 uA to 135 uA,9 and from 54 uA to 123 uA;P0.01, n=5, each). The basal TF latency without stimulation (3.1 sec) was reduced by the antagonists (to 2.5 sec by yohimbine, p<0.05, n=5; to 2.6 sec by naloxone, p<0.1, n=5), vehicle only did not show any effect. Noradrenaline(NA) in the spinal cord superfusates measured with HPLC was increased by the LC/SC stimulation, from 4.18 ng/ml before to 7.74 ng/ml after stimulation (P<0.05, n=10). The result suggest that analgesia induced by LC/SC stimulation is mediated, at least in part, by the noradrenergic system in which ${\alpha}_2$ receptor is involved, as well as the opioid system.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.4
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• pp.805-817
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• 2009

This study was to investigate central localization of neurons projecting to the urinary bladder and urinary bladder-related acupoints(Wijung, $BL_{40}$) and neurons of immunoreactive to hormones and hormone receptors regulating urinary bladder function by using peudorabies virus(PRV). In this experiment, Bartha's strain of pseudorabies virus was used in rats to trace central localization of urinary bladder-related neurons and urinary bladder-related acupoints($BL_{40}$) which can regulate urinary system. PRV was injected into the urinary bladder and acupoints($BL_{40}$) related urinary system. After six days survival of rats, mainly common labeled neurons projecting to the urinary bladder and urinary bladder-related acupoints were identified in spinal cord, medulla, pons and diencephalon by PRV immunohistochemical staining method. First-order PRV labeled neurons projecting to urinary bladder and urinary bladder-related acupoints were found in the cervical, thoracic, lumbar and sacral spinal cord. Commonly labeled preganglionic neurons were labeled in the lumbosacral spinal cord and thoracic spinal cord. They were found in the lateral horn area(sacral parasympathetic nucleus and intermediolateral nucleus), lamina V-X, intermediomedial nucleus and dorsal column area. The area of sensory neurons projecting to urinary bladder and Wijung($BL_{40}$) was L5-S2 spinal ganglia and T12-L1 spinal ganglia, respectively. In the brainstem, the neurons were labeled most evidently and consistently in the nucleus of tractus solitarius, area postrema, dorsal motor nucleus of vagus nerve, reticular nucleus, raphe nuclei(obscurus, magnus and pallidus), C3 adrenalin cells, parapyramidal area(lateral paragigantocellular nucleus), locus coeruleus, subcoeruleus nucleus, A5 cell group, Barrington's nucleus and periaqueductal gray matter. In the diencephalon, PRV labeled neurons were marked mostly in the paraventricular nucleus and a few ones were in the lateral hypothalamic nucleus, posterior hypothalamic nucleus, ventromedial hypothalamic nucleus, arcuate nucleus, median eminence, perifornical nucleus, periventricular nucleus and suprachiasmatic nucleus. In cerebral cortex, PRV labeled neurons were marked mostly in the frontal cortex, 1,2 area, hind limb area, agranular insular cortex. Immunoreactive neurons to Corticotropin releasiing factor(CRF), Corticotropin releasiing factor-receptor(CRF-R), c-fos and serotonin were a part of labeled areas among the virus-labeled neurons of urinary bladder and Wijung($BL_{40}$). The commonly labeled areas were nucleus tractus solitarius, area postrema, reticular nucleus, raphe nuclei(obscurus, magnus and pallidus), locus coeruleus, A5 cell group, Barrington,s nucleus, arcuate nucleus, paraventricular nucleus, frontal cortex 1, 2 area, hind limb, and perirhinal(agranular insular) cortex. These results suggest that overlapped CNS locations are related with autonomic nuclei which regulate the functions of urinary bladder-relate organs and it was revealed by tracing PRV labeled neurons projecting urinary bladder and urinary bladder-related acupoints. These commonly labeled areas often overlap with the neurons connected with hormones and hormone receptors related to urination.

• The Korean Journal of Pain
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• v.27 no.4
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• pp.313-320
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• 2014

Dexmedetomidine, an imidazoline compound, is a highly selective ${\alpha}_2$-adrenoceptor agonist with sympatholytic, sedative, amnestic, and analgesic properties. In order to minimize the patients' pain and anxiety during minimally invasive spine surgery (MISS) when compared to conventional surgery under general anesthesia, an adequate conscious sedation (CS) or monitored anesthetic care (MAC) should be provided. Commonly used intravenous sedatives and hypnotics, such as midazolam and propofol, are not suitable for operations in a prone position due to undesired respiratory depression. Dexmedetomidine converges on an endogenous non-rapid eye movement (NREM) sleep-promoting pathway to exert its sedative effects. The great merit of dexmedetomidine for CS or MAC is the ability of the operator to recognize nerve damage during percutaneous endoscopic lumbar discectomy, a representative MISS. However, there are 2 shortcomings for dexmedetomidine in MISS: hypotension/bradycardia and delayed emergence. Its hypotension/bradycardiac effects can be prevented by ketamine intraoperatively. Using atipamezole (an ${\alpha}_2$-adrenoceptor antagonist) might allow doctors to control the rate of recovery from procedural sedation in the future. MAC, with other analgesics such as ketorolac and opioids, creates ideal conditions for MISS. In conclusion, dexmedetomidine provides a favorable surgical condition in patients receiving MISS in a prone position due to its unique properties of conscious sedation followed by unconscious hypnosis with analgesia. However, no respiratory depression occurs based on the dexmedetomidine-related endogenous sleep pathways involves the inhibition of the locus coeruleus in the pons, which facilitates VLPO firing in the anterior hypothalamus.

• The Korea Journal of Herbology
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• v.26 no.2
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• pp.59-66
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• 2011

Objectives : The goal of this study was to investigate the antidepressant effects of Mixture of Lycii Radicis Cortex and Moutan Cortex on the change of HPA-Axis and Catecholamic system. Methods : We were performed the Forced Swimming Test. The expressions of Corticotropin-Releasing Factor (CRF) and c-Fos at paraventricular nucleus (PVN), and tyrosine hydroxylase (TH) at ventral tegmental area (VTA) and locus coeruleus (LC) were evaluated by immunohistochemical method. Results : The duration of immobility in the Forced Swimming Test was significantly decreased in A100, A400(p<0.05~p<0.01). CRF expressions at PVN was significantly decreased in A400(p<0.05).No other group showed significant difference in expression of c-Fos at PVN comparing with control group. TH expressions at VTA was significantly decreased in A100 and A400, respectively(p<0.001). TH expressions at LC was significantly decreased in A100(p<0.01). Conclusions : According to the above results, Mixture of Lycii Radicis Cortex and Moutan Cortex has antidepressant effects via the reduction of CRF expression and the Catecholamine System activity.

• Herbal Formula Science
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• v.15 no.2
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• pp.147-160
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• 2007

Objectives: This study is carried out to investigate the anti-stress effects of the sihoueokgantang in rats. Methods: we performed the passive avoidance test and the forced swimming test. The degrees of TH were also measured with immunohistochemical method in the regions of VTA and LC. Results: 1. As the results of the passive avoidance test. the sihoueokgantang showed tendency to improvement in compared with control group. 2. As the results of the forced swimming test, immobility of rats was significantly decreased in sihoueokgantang in compared with control group. 3. As the results of TH expression in the region of the LC, TH-immunoreactive cells were significantly decreased in the sihoueokgantang 100 mg/kg. As the results of TH expression in the region of the VTA. TH-immunoreactive cells were significantly decreased in the sihoueokgantang 400 mg/kg. Conclusion: As the results above, it can be considered that sihoueokgantang has the effects of preventing depression and memory decrease caused by stress.

• Herbal Formula Science
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• v.18 no.1
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• pp.155-167
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• 2010

Objectives : In order to investigate the antidepressant effects of Forsythiae Fructus(FF), we performed the Forced Swimming Test(FST). Also the expressions of corticotropin-releasing factor (CRF), c-Fos and tyrosine hydroxylase(TH) were measured by immunohistochemical method at paraventricular nucleus(PVN), ventral tegmental area(VTA) and locus coeruleus(LC). Methods : Spraque-Dawley rats were administered FF extract(100 mg/kg, 400 mg/kg) intragastrically three times prior to the FST. Results : The duration of immobility in the FST was significantly decreased in the FF 100 mg/kg, 400 mg/kg groups(p<0.05). The expression of CRF was significantly reduced in the FF 100 mg/kg and 400 mg/kg groups(p<0.001). c-Fos expression was significantly decreased at PVN in the FF 100 mg/kg group(p=0.069). TH expression at VTA was significantly increased in the FF 100 mg/kg and 400 mg/kg groups(p<0.05). TH expression at LC was not significantly changed(p=0.346). Conclusion : According to the results, it can be suggested that Forsythiae Fructus has antidepressant effect via the decreased immobility through the reduction of CRF and c-Fos expression at PVN.

• Herbal Formula Science
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• v.17 no.1
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• pp.163-173
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• 2009

Objectives : The goal of this study was to investigative the effect of Gardeniae Fructus (GF)as antidepressant in the forced swimming test(FST) model rats. Methods : The expressions of corticotropin-releasing factor(CRF), tyrosine hydroxylase (TH) and c-fos were measured by immunohistochemical method at paraventricular nucleus(PVN), locus coeruleus (LC) and ventral tegmental area(VTA). Results : The duration of immobility in FST was significantly decreased in the GF 100mg/kg groups (p<0.05). CRF expression was significantly decreased at PVN in the GF 100 mg/kg and 400mg/kg treated group in comparison with the control group, respectively (p<0.01). c-fos expression was decreased at PVN in the GF 100 mg/kg treated group with no significance. TH expression was significantly decreased in the GF 100 mg/kg and 400mg/kg treated group in comparison with the control group, at LC and VTA respectively (p<0.001). Conclusion : According to the results, it can be considered that Gardeniae Fructus has antidepressant effect by showing the reduction of immobility in FST through the reduction of CRF, TH expression.

• Herbal Formula Science
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• v.17 no.1
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• pp.129-140
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• 2009

Objectives : The goal of this study was to investigate the effect of Moutan Cortex as antidepressant in forced swimming test(FST) model. Methods : The expressions of corticotropin-releasing Factor(CRF), c-Fos and tyrosine hydroxylase(TH) were measured with immunohistochemical method at paraventricular nucleus (PVN), locus coeruleus(LC) and ventral tegmental area(VTA). Results : The duration of immobility in the forced swimming test was significantly decreased in the Moutan Cortex 100 mg/kg treated group in comparison with the control group(p<0.01). CRF and c-Fos expressions at PVN were decreased in the Moutan Cortex 100mg/kg treated group in comparison with the control group. But only the expression of c-Fos was shown the significance(p<0.05). TH expressions at LC and VTA were significantly decreased in the Moutan Cortex 100mg/kg and 400mg/kg treated group in comparison with the control group(p<0.001). Conclusion : According to the results, Moutan Cortex has the antidepressant effect by showing the reduced immobility through the reduction of c-Fos expression at PVN and the reduction of TH expression at LC and VTA.