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      • Nicotine-induced behavioral sensitization is associated with extracellular dopamine release and expression of c-Fos in the striatum and nucleus accumbens of the rat

        Shim, Insop,Javaid I. Javaid,David Wirtshafter,Jang, Soo-Yong,Shin, Kyung-Ho,Lee, Hye-Jung,Chung, Young-Cho,Chun, Boe-Gwun 경희대학교 동서의학연구소 2001 東西醫學硏究所 論文集 Vol.2001 No.-

        It is well known that repeated injections of nicotine produce progressively larget increases in locomotor activity, an effect referred to as behavioral sensitization. This study was carried out to investigate the neural mechanisms underlying nicotine-induced behavioral sensitization using in vivo microdialysis and Fos-like immunohistochemistry (FLI). Rats were given repeated injections of saline or nicotine (0.4 mg/kg s.c., twice daily for 7 days) followed by one challenge injection on the 4th day after the last daily injection. Systemic challenge with nicotine produced a much larger increase in locomotor activity in nicotine-pretreated rats (659.1±94.9 counts/2 h) than in saline-pretreated rats (218.1±6.1 counts/2 h). A direct local challenge of nicotine(1 or 5 mM) via a microdialysis probe in the nucleus accumbens or striatum induced a much greater dose-dependent increase of dopamine (DA) output in nicotine-pretreated rats than in saline-pretreated rats. Furthermore, in parallel with the behavioral and biochemical data, systemic challenge with nicotine produced marked Fos-like immunohischemistry in the nucleus accumbens and the striatum in the nicotine-pretreated rats. Taken together, this study demonstrates that behavioral sensitization is clearly associated with an increase in DA release and activation of Fos-like immunoreactive cells in the striatum and the nucleus accumbens produced by repeated nicotine treatment. Our results strongly suggest that the striatum and the nucleus accumbens may play a major role in nicotine-induced behavioral sensitization. The present results are discussed in terms of the development and expression of nicotine-induced behavioral sensitization. ⓒ 2001 Elsevier Science B.V. All rights reserved.

      • Effect of Ginseng Total Saponin on Extracellular Dopamine Release Elicited by Local Infusion of Nicotine into the Striatum of Freely Moving Rats

        Shim, Insop,Javaid, J.I.,Kim, Sang-Eun 경희대학교 동서의학연구소 2001 東西醫學硏究所 論文集 Vol.2000 No.-

        We investigated the effect of ginseng total saponin(GTS) on nicotine-induced dopamine(DA) release in the striatum of freely moving rats using an in vivo microdialysis technique. In order to further characterize the mechanism by which GTS affects DA release, the effect of GTS on K+-induced DA released was also examined. Local infusion of nicotine(1, 5, and 10 mM) into the striatum produced a dose-dependent increase in extracellular DA in dialysate samples (maximal response = 154.0 ± 10.8%, 308.1 ± 55.7%, and 499.9 ± 77.9% over basal levels, respectively). GTS(100mg/kg i.p.) had no effect on basal levels of extracellular DA. However. GTS inhibited maximal DA release induced by intra-striatal infusion of nicotine (1, 5, and 10 mM) by 35.3%, 36.6%, and 58.5%, respectively. Intra-striatal infusion of high K+ solution (100mM) produced and increase in extracellular DA in the striatum(maximal response = 796.6 ± 98.8% over basal levels). However, GTS had no effect on the K+-induced increase in extracellular DA. The present study demeonstrated that GTS inhibited striatal DA release stimulated by local infusion of nicotine. This may reflect the blocking effect of GTS on the striatum-related behavior induced by nicotine as well as other psychostimulants. The results also suggest that GTS may act on presynaptic nicotinic acetylcholine receptors or receptor-operated Na+ channels in dopaminergic nerve terminals, but not on voltage-sensitive ion channels

      • SCOPUSKCI등재

        The role of the supramammillary area of the hypothalamus in cognitive functions

        Shim, Hyun Soo,Park, Hyun-Jung,Lee, Mi-Sook,Ye, Minsook,Shim, Insop 한국통합생물학회 2018 Animal cells and systems Vol.22 No.1

        The supramammillary area (SUM) of the hypothalamus has wide spread connection with numerous brain structures. It is known that the SUM can control the frequency of the hippocampal theta rhythm, which plays a role in the cognitive functions of the hippocampal formation. In order to examine the role of the specific cells of the SUM in learning and memory, selective cholinergic neurotoxic or excitotoxic lesioned rats of the SUM were tested for spatial memory on the Morris water maze (MWM) test. After the behavior tests, the expression of acetylcholinesterase (AChE) in the hippocampus was studied using the immunohistochemistry. In the MWM test, both lesion of the SUM with 192 IgG-saporin or ibotenic acid produced the impairment of spatial learning and memory. The expression of AChE immunreactive neurons in the hippocampal CA3 region was decreased after injections of 192 IgG-saporin into the SUM. These findings suggest that cholinoceptive cells of the SUM area may play a critical role in the process of learning and memory.

      • KCI등재
      • KCI등재
      • SCIESCOPUSKCI등재

        Berberine alleviates symptoms of anxiety by enhancing dopamine expression in rats with post-traumatic stress disorder

        Lee, Bombi,Shim, Insop,Lee, Hyejung,Hahm, Dae-Hyun The Korean Society of Pharmacology 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.2

        Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, anxiety, depression, and amnesic symptoms that may involve the release of monoamines in the fear circuit. The present study measured several anxiety-related behavioral responses to examine the effects of berberine (BER) on symptoms of anxiety in rats after single prolonged stress (SPS) exposure, and to determine if BER reversed the dopamine (DA) dysfunction. Rats received BER (10, 20, or 30 mg/kg, intraperitoneally, once daily) for 14 days after SPS exposure. BER administration significantly increased the time spent in the open arms and reduced grooming behavior during the elevated plus maze test, and increased the time spent in the central zone and the number of central zone crossings in the open field test. BER restored neurochemical abnormalities and the SPS-induced decrease in DA tissue levels in the hippocampus and striatum. The increased DA concentration during BER treatment may partly be attributed to mRNA expression of tyrosine hydroxylase and the DA transporter in the hippocampus, while BER exerted no significant effects on vesicular monoamine transporter mRNA expression in the hippocampus of rats with PTSD. These results suggest that BER had anxiolytic-like effects on behavioral and biochemical measures associated with anxiety. These findings support a role for reduced anxiety altered DAergic transmission and reduced anxiety in rats with PTSD. Thus, BER may be a useful agent to treat or alleviate psychiatric disorders like those observed in patients with PTSD.

      • SCIESCOPUSKCI등재

        Tetramethylpyrazine reverses anxiety-like behaviors in a rat model of post-traumatic stress disorder

        Lee, Bombi,Shim, Insop,Lee, Hyejung,Hahm, Dae-Hyun The Korean Society of Pharmacology 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.5

        Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, and anxiety that may involve the release of monoamines in the fear circuit. The reported pharmacological properties of tetramethylpyrazine (TMP) include anti-cancer, anti-diabetic, anti-atherosclerotic, and neuropsychiatric activities. However, the anxiolytic-like effects of TMP and its mechanism of action in PTSD are unclear. This study measured several anxiety-related behavioral responses to examine the effects of TMP on symptoms of anxiety in rats after single prolonged stress (SPS) exposure by reversing the serotonin (5-HT) and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Rats were given TMP (10, 20, or 40 mg/kg, i.p.) for 14 days after SPS exposure. Administration of TMP significantly reduced grooming behavior, increased the time spent and number of visits to the open arm in the elevated plus maze test, and significantly increased the number of central zone crossings in the open field test. TMP administration significantly reduced the freezing response to contextual fear conditioning and significantly restored the neurochemical abnormalities and the SPS-induced decrease in 5-HT tissue levels in the prefrontal cortex and hippocampus. The increased 5-HT concentration during TMP treatment might be partially attribute to the tryptophan and 5-hydroxyindoleacetic acid mRNA level expression in the hippocampus of rats with PTSD. These findings support a role for reducing the altered serotonergic transmission in rats with PTSD. TMP simultaneously attenuated the HPA axis dysfunction. Therefore, TMP may be useful for developing an agent for treating psychiatric disorders, such those observed in patients with PTSD.

      • SCOPUSKCI등재

        The polymethoxylated flavone, Tangeretin improves cognitive memory in rats experiencing a single episode of prolonged post-traumatic stress

        Lee, Bombi,Shim, Insop,Lee, Hyejung,Hahm, Dae-Hyun The Korean Society for Integrative Biology 2018 Animal cells and systems Vol.22 No.1

        Post-traumatic stress disorder (PTSD) is a stress-related psychiatric/mental condition. Tangeretin (TAN), a major polymethoxylated flavone of citrus plants, exhibits anti-inflammatory and neuroprotective activities. However, whether TAN leads to cognitive improvement in PTSD patients remains unclear. In the present study, we explored whether TAN improved cognitive impairment induced in rats by single prolonged stress (SPS episode mimicking PTSD induction) and determined whether TAN reversed reductions in dopamine (DA) and serotonin (5-HT) levels. Rats were intraperitoneally injected with TAN for 14 consecutive days after the SPS, which had induced cognitive deficits evident in the object recognition task and the Morris water maze test; the impairments were improved by TAN (100 mg/kg). TAN rescued the neurochemical abnormalities and the SPS-induced decreases in DA and 5-HT levels in the hippocampus and amygdala. These effects may be attributable in part to induction of hippocampal genes encoding tyrosine hydroxylase and tryptophan hydroxylase-1. Our results support the idea that rats with PTSD exhibit changes in DAergic and serotonergic transmission and in memory impairment. Thus, TAN mediated reversal of memory-related behavioral dysfunction associated with traumatic stress may be a useful therapeutic intervention in PTSD patients.

      • SCIESCOPUSKCI등재

        Berberine alleviates symptoms of anxiety by enhancing dopamine expression in rats with post-traumatic stress disorder

        Bombi Lee,Insop Shim,Hyejung Lee,Dae-Hyun Hahm 대한생리학회-대한약리학회 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.2

        Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, anxiety, depression, and amnesic symptoms that may involve the release of monoamines in the fear circuit. The present study measured several anxiety-related behavioral responses to examine the effects of berberine (BER) on symptoms of anxiety in rats after single prolonged stress (SPS) exposure, and to determine if BER reversed the dopamine (DA) dysfunction. Rats received BER (10, 20, or 30 mg/kg, intraperitoneally, once daily) for 14 days after SPS exposure. BER administration significantly increased the time spent in the open arms and reduced grooming behavior during the elevated plus maze test, and increased the time spent in the central zone and the number of central zone crossings in the open field test. BER restored neurochemical abnormalities and the SPS-induced decrease in DA tissue levels in the hippocampus and striatum. The increased DA concentration during BER treatment may partly be attributed to mRNA expression of tyrosine hydroxylase and the DA transporter in the hippocampus, while BER exerted no significant effects on vesicular monoamine transporter mRNA expression in the hippocampus of rats with PTSD. These results suggest that BER had anxiolytic-like effects on behavioral and biochemical measures associated with anxiety. These findings support a role for reduced anxiety altered DAergic transmission and reduced anxiety in rats with PTSD. Thus, BER may be a useful agent to treat or alleviate psychiatric disorders like those observed in patients with PTSD.

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