• The Journal of Pediatrics of Korean Medicine
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• v.20 no.1
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• pp.137-149
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• 2006

Objective : The purpose of this study is to investigate the effect of Radix Scutellariae on repeated nicotine-induced locomotor activity and c-Fos expression utilizing Fos-like immuno-histochemistry method in the nucleus accumbens, and the striatum, one of the major projection areas of the control DA system. Methods : Male Sprague-Dawley rats were divided into untreated(normal), nicotine-treated (control), Radix Scutellariae-treated(sample) groups, RS group received Radix Scutellariae(100mg/kg, i.p.) 30minutes before injection of nicotine(0.4mg/kg, s.c.) for 7days. Rat were followed withdrawal for 3 days and one challenge for 1day. Results : Systemic challenge with nicotine produced a much larger locomotor activity and expression of c-Fos in the nucleus accumbens and the striatum. Pretreatment with Radix Scutellariae decreased in nicotine-induced locomotor activity and c-Fos expression in the core, shell, straitum area. Conclusion : These results demonstrated that reduction in locomotor activity by Radix Scutellariae may be mediated by reduction of dopamine release and of postsynaptic neuronal activity in striatum, the nucleus accumbens. Out results show neurochemical evidence for the biological effects of Radix Scutellariae that ultimately may help us to understand how Radix Scutellariae can be used to treat nicotine addiction.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.1
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• pp.79-85
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• 2021

α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors are differentially regulated in the nucleus accumbens (NAcc) of the brain after cocaine exposure. However, these results are supported only by biochemical and electrophysiological methods, but have not been validated with immunohistochemistry. To overcome the restriction of antigen loss on the postsynaptic target molecules that occurs during perfusion-fixation, we adopted an immersion-fixation method that enabled us to immunohistochemically quantify the expression levels of the AMPA receptor GluA1 subunit in the NAcc. Interestingly, compared to saline exposure, cocaine significantly increased the immunofluorescence intensity of GluA1 in two sub-regions, the core and the shell, of the NAcc on withdrawal day 21 following cocaine exposure, which led to locomotor sensitization. Increases in GluA1 intensity were observed in both the extra-post synaptic density (PSD) and PSD areas in the two sub-regions of the NAcc. These results clearly indicate that AMPA receptor plasticity, as exemplified by GluA1, in the NAcc can be visually detected by immunohistochemistry and confocal imaging. These results expand our understanding of the molecular changes occurring in neuronal synapses by adding a new form of analysis to conventional biochemical and electrophysiological methods.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.1
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• pp.59-65
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• 2022

Phosphorylation levels of glycogen synthase kinase 3β (GSK3β) negatively correlated with psychomotor stimulant-induced locomotor activity. Locomotor sensitization induced by psychomotor stimulants was previously shown to selectively accompany the decrease of GSK3β phosphorylation in the nucleus accumbens (NAcc) core, suggesting that intact GSK3β activity in this region is necessary for psychomotor stimulants to produce locomotor sensitization. Similarly, GSK3β in the NAcc was also implicated in mediating the conditioned effects formed by the associations of psychomotor stimulants. However, it remains undetermined whether GSK3β plays a differential role in the two sub-regions (core and shell) of the NAcc in the expression of drug-conditioned behaviors. In the present study, we found that GSK3β phosphorylation was significantly lower in the NAcc shell obtained from rats expressing amphetamine (AMPH)-induced conditioned locomotor activity. Further, we demonstrated that these effects were normalized by treatment with lithium chloride, a GSK3β inhibitor. These results suggest that the behavior produced by AMPH itself and a conditioned behavior formed by associations with AMPH are differentially mediated by the two sub-regions of the NAcc.

• Animal cells and systems
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• v.8 no.4
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• pp.319-328
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• 2004

Extrinsic connections between the cortex of the superior temporal sulcus (STS) and the ventral striatum in pigtail macaque monkeys (Macacca nemestrina) were studied by injection of retrograde tracers into the ventromedial caudate nucleus, the ventral and central shells of the nucleus accumbens (NA), the dorsal core of the NA, and the ventrolateral putamen. In the present study, we demonstrate that the projections from the unimodal (area TAa, IPa, TEa, and TEm) and the multimodal (area TPO and PGa) sensory association areas in the STS mainly terminate in the ventromedial caudate nucleus as well as in the ventral and central shells of the NA. However, there are only few projections to the dorsal core of the NA and the ventrolateral putamen from the sensory association cortex in the STS. Based on these differential neural connections between the subterritories of the ventral striatum and the sensory association areas, the ventromedial caudate nucleus and the shells of NA appear to be major integration sites for sensory input from the STS and functionally different from the dorsal core of NA and the ventrolateral putamen.

• 대한약리학회:학술대회논문집
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• 2006.10a
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• pp.116.2-116.2
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• 2006

• Applied Microscopy
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• v.35 no.3
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• pp.135-152
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• 2005

Prefrontal cortex is a psychological and metaphysical cortex, which deals with feeling, memory, planning, attention, personality, etc. And it also integrates above-mentioned events with motor control and locomotor activities. Prefrontal cortex works as a highest CNS center, since the above mentioned functions are very important for one's successful life, and further more they are upgraded every moments through memory and learning. Many of these highest functions are supposed to be generated via forebrain basal nuclei (caudate nucleus, fundus striati nucleus, accumbens septi nucleus, septal nucleus, etc.). In this experiment, prefrontal efferent terminals within basal forebrain nuclei were ultrastructurally studied. Spraque Dawley rats, weighing $250{\sim}300g$ each, were anesthetized and their heads were fixed on the stereotaxic apparatus (experimental model, David Kopf Co.). Rats were incised their scalp, perforated a 3mm-wide hole on the right side of skull at the 11mm anterior point from the frontal O point (Ref. 13, Fig. 1), suctioned out the prefrontal cortex including cortex of the frontal pole, with suction instrument. Two days following the operations, small tissue blocks of basal forebrain nuclei were punched out, fixed in 1% glutaraldehyde-1% paraformaldehyde solution followed by 2% osmium tetroxide solutions. Ultrathin sections were stained with 1% borax-toluidin blue solution, and the stained sections were obserbed with an electron microscope. Degenerating axon terminals were found within all the basal forbrain nuclei. Numbers of degenerated terminals were largest in the caudate nucleus, next in order, in the fundus striati nucleus, in the accumbens septi nucleus, and the least in the septal nucleus. Only axospinous terminals were degenerated within the caudate nucleus and the fundus striati nucleus, and they showed the characters of striatal motor control system. Axodendritic and axospinous terminals were degenerated within the accumbens septi nucleus and the lateral septal nucleus, and they showed the characters of visceral limbic system. Prefrontal role in integrating the limbic system with the striatal system, en route basal forebrain nuclei, was discussed.

• Archives of Pharmacal Research
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• v.9 no.3
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• pp.169-174
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• 1986

Bilateral lesion of nucleus accumbens septi (N, AB), one of the mesolimbic nuclei, resulted in hyperirritability and muricide including mouse eating behavior in rats. The effects of various drugs on hyperirritability and muricide induced by NAB lesion were investigated in rats. Hyperirritability in NAB rats were significantly reduced by L-DOPA L-5-HTP major and minor tranquilizers but not reduced by MA, ATP and imipriamine-like antidepressants. On the other hand, muricide in NAB rats was significantly suppressed by L-DOPA, L-5-HTP, major and minor tranquilizers, furthermore, selectively suppressed by MA, ATP and antidepressants. These results suggested that the neural mechanism for inducing muricide is distinct from for hyperirritability in NAB rats, and that muricide in NAB rats is resulted from the increasing of cholinergic activity and reduction of dopaminergic and serotonergic activity.

• Korean Journal of Biological Psychiatry
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• v.8 no.1
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• pp.79-84
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• 2001

Objectives : To investigate the effects of (-)-3-PPP(0.5, 2, and 10mg/kg, s.c.) and haloperidol(0.1, 0.5, and 2mg/kg, s.c.) on the extracellular dopamine concentrations, and the effect of pretreatment with (-)-3-PPP(2mg/kg) on the haloperidol(2mg/kg)-induced extracellular dopamine concentrations in the nucleus accumbens(NAS) of free moving rats. Methods : Dopamine levels in dialysate were determined with high pressure liquid chromatography(HPLC) with electrochemical detection(ECD). Results : (1)(-)-3-PPP had dual actions depending on the doses: at 2mg/kg, it decreased and at 10mg/kg, increased extracellular dopamine concentrations ; (2) haloperidol at all doses increased dopamine levels with higher dose having a greater increase; and (3) pretreatment of (-)-3-PPP reduced the increase in dopamine levels elicited by acute treatment with haloperidol. Conclusions : These findings suggest that pretreatment of (-)-3-PPP in low dose could accelerate the onset of therapeutic effect of haloperidol by diminishing the haloperidol-induced dopamine release in the limbic system.

• Herbal Formula Science
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• v.22 no.1
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• pp.105-112
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• 2014

Background and objective: Methamphetamine (Meth) is a widely abused psychostimulant that produces hyperlocomotion in rodents. Radix of Glycyrrhizae uralensis comprises a variety of bioactive components that have neuroprotective effects. In a previous study, we have demonstrated methanol extracts from radix of Glycyrrhizae uralensis (MEGR) suppress acute cocaine-induced extracellular dopamine release in the nucleus accumbens. In the present study, we investigated the effect of MEGR on acute Meth-induced hyperlocomotion. Methods: Male Sprague-Dawley rats were orally administered with MEGR (60 mg/kg and 180 mg/kg) 60 min prior to an intraperitoneal injection of Meth (1.0 mg/kg). Results: Behavioral analysis showed acute Meth greatly increased locomotor activities, while pretreatment with MEGR dose dependently inhibited the hyperlocomotion. In parallel, there were markedly increased levels of dopamine and its metabolite 3, 4-dihydroxyphenylacetic acid in the nucleus accumbens tissues in Meth-treated rats, which were also almost completely reversed by 180 mg/kg MEGR. Conclusions: These results showed that radix of Glycyrrhizae uralensis attenuates Meth-induced hyperlocomotion by inhibiting dopamine synthesis and utilization, suggesting that radix of Glycyrrhizae uralensis might be effective in blocking the rewarding effect of Meth.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.6
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• pp.389-395
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• 2011

Repeated administration of psychostimulants such as cocaine leads to the development of behavioral sensitization. Extracellular signal-Regulated Kinase (ERK), an enzyme important for long-term neuronal plasticity, has been implicated in such effects of these drugs. Although the nucleus accumbens (NAcc) is the site mediating the expression of behavioral sensitization by drugs of abuse, the precise role of ERK activation in this site has not been determined. In this study we demonstrate that blockade of ERK phosphorylation in the NAcc by a single bilateral microinjections of PD98059 (0.5 or $2.0{\mu}g/side$), or U0126 (0.1 or $1.0{\mu}g/side$), into this site dose-dependently inhibited the expression of cocaine-induced behavioral sensitization when measured at day 7 following 6 consecutive daily cocaine injections (15 mg/kg, i.p.). Acute microinjection of either vehicle or PD98059 alone produced no different locomotor activity compared to saline control. Further, microinjection of PD98059 ($2.0{\mu}g/side$) in the NAcc specifically lowered cocaine-induced increase of ERK phosphorylation levels in this site, while unaffecting p-38 protein levels. These results indicate that ERK activation in the NAcc is necessary for the expression of cocaine-induced behavioral sensitization, and further suggest that repeated cocaine evokes neuronal plasticity involving ERK pathway in this site leading to long-lasting behavioral changes.