• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.3
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• pp.281-286
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• 2012

The present study was designed to investigate the effect of Rehmannia glutinosa on phosphorylation of extracellular signal-regulated kinase(ERK) and cAMP response element-binding protein(CREB) in the acute cocaine-treated rats. Rats orally received vehicle or extract of Rehmannia glutinosa 1 h prior to saline (1 ml/kg, i.p.) or cocaine hydrochloride (20 mg/kg, i.p.) treatment. Rats were sacrificed 15 min after a single intraperitoneal injection of saline or cocaine. Rehmannia glutinosa at dose of 50 mg/kg significantly decreased phosphorylation of ERK, CREB and Elk-1 in the nucleus accumbens and striatum of the cocaine-treated rat brain by immunocytochemistry. These results suggest that Rehmannia glutinosa may contribute to the effects of cocaine on gene expression and on behaviors.

• Animal cells and systems
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• v.7 no.3
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• pp.237-248
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• 2003

Recent evidence on behaviors in macaque monkeys indicate that the medial temporal cortical areas such as the entorhinal cortex (EC), perirhinal cortex, and parahippocampal cortex (PHC) are importantly involved in limbic and sensory memory function. Neuroanatomical studies also have demonstrated that the medial temporal cortical areas are connected with the ventral striatum, although comparatively little is known about the precise topography of these connections. We investigated the topographic organization of connections between the medial temporal cortical areas and the ventral striatum by placing retrograde tracers into five different regions of the ventral striatum: the ventromedial caudate nucleus, ventral shell, central shell, dorsal core of the nucleus accumbens (NA), and ventrolateral putamen. We found that the shell of the NA was the main projection site from the medial temporal cortical areas. Within the shell of the NA, there were also differential connections: EC diffusely innervates shell of the NA, while the projections from the perirhinal cortex and PHC concentrate on the ventral shell of the NA. Taken together, it is possible that the ventral shell of the NA is the main integration site of the limbic and sensory memory coming from the EC, perirhinal cortex, and PHC.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.4
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• pp.299-305
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• 2001

Activation of D1-like dopamine receptors by psychostimulants, such as amphetamine, upregulates the expression of immediate early gene and opioid peptide gene in the striatum. The genomic changes are regulated by phosphorylated transcription factors via complicated intracellular events. To evaluate temporal expression of the transcription factors by dopaminergic stimulation, the D1-like dopamine agonist, amphetamine or SKF82958, was systematically delivered. As intracellular markers in response to the agonist, phosphorylated cAMP response element-binding protein (pCREB), Fos-related antigens (FRA) and FosB immunoreactivity (IR) was compared at 20 and 120 min time points in the selected areas of the striatum. Semi-quantitative immunocytochemistry showed that amphetamine (5 mg/kg, i.p.) significantly increased pCREB-IR at 20 min, sustained up to 60 min and decreased at 120 min after the infusion. Like amphetamine, the full D1 agonist, SKF82958 (0.5 mg/kg, s.c.), also increased pCREB-IR at 20 min, but not at 120 min after the infusion in the dorsal striatum (caudoputaman, CPu) and shell of ventral striatum (nucleus accumbens, NAc). In contrast, FRA- and FosB-IR induced by SKF82958 was significantly increased at 120 min, but not at 20 min after the administration. These data indicate that SKF82958 mimics induction of CREB phosphorylation by amphetamine and differentially regulates temporal induction of pCREB, and FRA and FosB expression in the striatum.

• Applied Microscopy
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• v.18 no.1
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• pp.1-20
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• 1988

There's been arguments on the different morphological status between the nucleus accumbens septi and nucleus fundus striati of ventral striatum. Authors carried out the comparative study on the neuronal cell types of these nuclei, in the chick and the rat. Results are summarized as follows: In the nucleus accumbens septi of the chick, there found 3 main cell types. Type I cells are oval or spindle-shaped. They are the most abundant cell types, comprising more than 80% of neurons. The pale nucleus is usually indented. The cytoplasm is also pale and contains small amount of mitochondria, rough r-ER and Golgi complexes. This cell has a few symmetric synapses on the cell membrane. Type II cells are pale large cells. They are polygonal or irregularly-shaped. They contain pale spherical nucleus, and the pale cytoplasm with relatively large amount of mitochondria, free ribosomes and well-developed Golgi complexes. Some axo-somatic synapes are found on the cell. Type III cells are oval or spherical-shaped. The nucleus is relatively pale and large, In the dense cytoplasm, well developed. r-ER formed typical Nissl's body, and there found many mitochondria, ribosomes and lysosomes. In the chick fundus striati nucleus, there also found 3 main cell types. Type I cells are small and spindle-shaped. This type is the most abundant one and constitutes more the 80% of the neurons. Morphological features other than it's shape, is generally similar with that of Type I cell in the nucleus accumbens. Type II cells are irregularly shaped large cells. Dense cytoplasm contains large amount of cell organelles. Some axo-somatic synapses are found. Type III cells are small dense cells. This oval cell contains the oval nucleus, and the plentiful cytoplasm with well developed r-ER, ribosomes and mitochondria. In the nucleus accumbens septi of the rat, there found 4 main cell types. Type I cells are small, oval or spherical cells, comprising more than 90% of all the neurons. Spherical nucleus shows typical chromatin rim along the nuclear membrane. Dense cytoplasm contains many ribosomes and mitochondria. Type II cells are large oval cells. The eccentric nucleus is deeply invaginated. Pale cytoplasm contains large amount of ribosomes, Golgi complexes, mitochondria, and dense bodies. Type III cells are pale, large, oval cells. They contain moderate amount of ribosomes and mitochondria, and some scattered stacks of r-ER. Type IV cells are small pale cells. Small oval nucleus is indented and shows chromatin rim. Only small amount of ribosomes and mitochondria can be found. In the nucleus fundus striati of the rat, there also found 4 main cell types. Type I cells are spherical or oval cells, comprising more than 90% of the neurons. The chromatin rim of the spherical nucleus is not so prominent as compared to the rim of type I cell in the nucleus accumbens septi. The cytoplasm contains moderate amount of mitochondria, ribosomes and some scattered r-ER. A few axo-somatic synapses were found. Type II cells are small round or polygonal cells. Golgi complexes are especially well-developed in this cell type. The cytoplasm also contains moderate amount of mitochondria, ribosomes, and dense bodies. Type III cells are small cells. The large nucleus shows prominent chromatin rim. The cytoplasm contains many ribosomes and mitochondria. Type IV cells are large, spheircal or oval cells. The nucleus is deeply indented. The plentiful cytoplasm contains large amount of ribosomes, mitochondria, Golgi complexes, neurotubules, but not r-ER. In the present study, it is clear that the nucleus accumbens septi and the nucleus fundus striati are independant cell groups, according to their cytoarchitectonics and the ultrastructural features of their cell types.

• Journal of Acupuncture Research
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• v.26 no.1
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• pp.39-47
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• 2009

Objectives : The mesolimbic dopamine system is believed to play a major role in the reinforcing effect and behavioral hyperactivity of abused drugs including methamphetamine. In the present study, the effect of acupuncture on methamphetamine-induced locomotor activity and c-Fos expression in the striatum and nucleus accumbens of rats were examined. Methods : Male Sprague-Dawley rats received acupuncture at bilateral Yanggu($SI_5$) point for 30seconds immediately before the subcutaneous injection of saline or methamphetamine(0.5mg/kg). The total amount of locomotor activity for 90min were measured just before brain samples were taken for immunohistochemistry. Results : Results showed that acupuncture at the specific point $SI_5$, but not control point(Kunlun, $BL_{60}$) significantly reduced locomotor activity and c-Fos expression in the striatum and nucleus accumbens induced by acute administration of methamphetamine. Conclusions : These results suggest that acupuncture may be effective in suppressing the reinforcing effect of methamphetamine by regulating neuronal activity.

• Herbal Formula Science
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• v.19 no.2
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• pp.39-46
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• 2011

Objectives : The BangPungTongSungSan(BPTSS) has been used as a therapeutic agent for cerebrovascular disease, cerebral hemorrhage, hypertension, diabetes and obesity in oriental medicine. The present study designed to investigate the effect of BPTSS on behavioral change and neuronal activation induced by acute methamphetamine(METH, 2 mg/kg, i.p.) in C57BL/6 mice. Methods : Mice received the oral administration of BPTTS(25, 50 and 100 mg/kg) 1 h prior to saline or METH administration. Locomotor activity was measured for 90 min using videotractking method and c-Fos expression, as marker of neuronal activation, was identified in a separate groups of mice by immunohistochemistry. Results and conclusions : Methamphetamine injection significantly increased locomotor activity and c-Fos expression in the nucleus accumbens and striatum. Interestingly, BPTTS(100 mg/kg) significantly suppressed locomotor activity and c-Fos expression in the nucleus accumbens and striatum by acute exposure to METH. These results suggest that BangPungTongSungSan may be effective in suppressing the reinforcing effect of methamphetamine by modulation neuronal activity.

• Journal of Oriental Neuropsychiatry
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• v.14 no.1
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• pp.85-106
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• 2003

Studies have shown that both the psychomotor stimulant effects and rewarding properties of addictive drugs, including morphine, are sensitized by repeated drug administration and it is suggested that both of these effects are mediated by the same or closely overlapping dopamine systems. Specifically, the mesolimbic dopamine system has been implicated in the reinforcing and sensitizing properties of morphine. In oriental medicine, Shenmen (HT7) point on the heart channel has been used to treat mental and psychosomatic disorders. This study was designed to investigate the effect of acupuncture on acute and repeated morphine-induced changes in extracellular dopamine levels using in vivo microdialysis and morphine-induced behavioral changes. In the morphine sensitization experiment, male Sprague-Dawley rats were treated twice a day for three days with increasing doses of morphine (10, 20 and 40 mg/kg, s.c.) or with saline. After 15 days of withdrawal, rats were challenged with morphine hydrochloride (5mg/kg, s.c.). Acupuncture was applied at bilateral Shenmen (HT7) points for 1 min after the morphine challenge. In the acute experiment, rats also received acupuncture for 1 min after an injection of morphine hydrochloride (5 mg/kg, s.c.). Results showed that acupuncture at the specific acupoint HT7, but not at control points (tail) significantly decreased both dopamine release and behavior induced by a systemic morphine challenge or a single sc morphine injection in the acute animals. These results suggest that reduction in sensitization may be one mechanism whereby acupuncture alleviates morphine craving in addicts.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.510-517
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• 2003

Studies have shown that both the psychomotor stimulant effects and rewarding properties of addictive drugs, including morphine, are sensitized by repeated drug administration and it is suggested that both of these effects are mediated by the same or closely overlapping dopamine systems. Specifically, the mesolimbic dopamine system has been implicated in the reinforcing and sensitizing properties of morphine. In oriental medicine, Shenmen (HT7) point on the heart channel has been used to treat mental and psychosomatic disorders. This study was designed to investigate the effect of acupuncture on acute and repeated morphine-induced changes in extracellular dopamine levels using in vivo microdialysis and morphine-induced behavioral changes. In the morphine sensitization experiment, male Sprague-Dawley rats were treated twice a day for three days with increasing doses of morphine (10, 20 and 40 mg/kg, s.c.) or with saline. After 15 days of withdrawal, rats were challenged with morphine hydrochloride (5 mg/kg, s.c.). Acupuncture was applied at bilateral Shenmen (HT7) points for 1 min after the morphine challenge. In the acute experiment, rats also received acupuncture for 1 min after an injection of morphine hydrochloride (5 mg/kg, s.c.). Results showed that acupuncture at the specific acupoint HT7, but not at control points (tail) significantly decreased both dopamine release and behavior induced by a systemic morphine challenge or a single sc morphine injection in the acute animals. These results suggest that reduction in sensitization may be one mechanism whereby acupuncture alleviates morphine craving in addicts.

• Archives of Pharmacal Research
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• v.25 no.3
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• pp.370-374
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• 2002

Administration of dopamine agonist, apomorphine (2 mg/kg, s.c.), produces cage climbing behavior in mice that exhibit typical dopaminergic stimulation. The present study investigated the pCREB expression level in several brain regions following apomorphine treatment in order to determine whether the increased the dopaminergic activation produced by apomorphine accompanies the changes in pCREB immunoreactivity. A mouse brain was removed at 0min, 10 min, 30 min, 1 h, 2 h, 7 h, and 24 h after apomorphine treatment. The brain tissue was fixed by an intracardiac perfusion with ice-cold 4％ paraformaldehyde in PBS. Immunohistochemical study was conducted using the ABC-DAB method. The data showed that the immunoreactivity of pCREB increased in the striatum, nucleus-accumbens, piriform cortex and the dentate gyrus of the hippocampus of a mouse brain 30 min after the apomorphine treatment. Increased immunoreactivity began to diminish 2 h after the apomorphine treatment in all the brain regions measured. The time course for the pCREB immunoreactivity was similar to the behavioral response induced by the apomorphine treatment. These results suggest that activation of the dopamine receptor is accompanied by an increase in pCREB expression in the mouse brain.

• Biomolecules & Therapeutics
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• v.9 no.2
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• pp.88-95
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• 2001

(+)-Methamphetamine (METH) is a psychostimulant, which has been the most popular abused drug in Korea. The rewarding mechanism in METH abuse has been reported to be mediated by dopaminergic system. Recently, it has been reported that dopamine releaser (phentermine) plays a dominant role in the discriminative stimulus effects of METH, whereas 5-HT releaser (fenfluramine) can strongly modify METH self-administration. The present study is designed to assess the behavioral changes and the changes of the serotonin receptors in the brains of rats administered repeated of self-administered METH. The repeated administration of 1.0 mg/kg/day METH for 12 days increased locomotor activities, and there was no difference between i.v. and i.p. treatment. Rats had actively acquired METH self-administration for 3 weeks at 0.1 or 0.2 mg/kg/injection. Whereas, it was taken few days to acquire sucrose pellet self-administration. The binding of [$^3$H]-8-hydroxy-DPAT (5-H $T_{1A}$ receptors) and [$^3$H]-5-carboxytryptamine (5-H $T_{1B}$ receptors) to brain sections was examined. Both passive administration and self-administration of METH did not change significantly the serotonin receptors levels in hippocampus, striatum and nucleus accumbens. These results suggest that serotonin receptors may not change in the acquisition period of METH self-administration, and we are trying to investigate the serotonin receptors levels of brain in rats maintained of METH self-administration.n.n.