• Biomolecules & Therapeutics
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• 제20권2호
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• pp.234-238
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• 2012

Propofol is an anesthetic commonly used to provide sedation or to induce and maintain an anesthetic stated. However, there are reports which indicate propofol may cause psychological dependence or be abused. In the present study, we used various behavioral tests including climbing test, jumping test, conditioned place preference, and self-administration test to assess the dependence potential and abuse liability of propofol compared to a positive control (methamphetamine) or a negative control (saline or intralipid). Among the tests, the conditioned place preference test was conducted with a biased method, and the selfadministration test was performed under a fixed ratio (FR) 1 schedule, 1 h per session. No difference was found in the climbing test and jumping test, but propofol (30 mg/kg, i.p.) increased the rewarding effect in the conditioned place preference test, and it showed a positive reinforcing effect compared to the vehicle. These results indicate that propofol tends to show psychological dependence rather than physical dependence, and it seems not to be related with dopaminergic system.

• Korean Journal of Acupuncture
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• 제19권1호
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• pp.25-33
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• 2002

Substantial evidence suggests that behavioral and reinforcing effects of cocaine can be mediated by the mesolimbic dopaminergic system. Injections of cocaine can produce one of the immediate-early gene, c-fos expression in the brain and behavioral activation. Acupuncture as a therapeutic intervention is widely used for the treatment of many mental disorders such as drugs of abuse. In order to investigate whether acupuncture has an influence on cocaine-induced reinforcing and behavioral effects, we examined the effect of acupuncture on cocaine-induced locomotor activity and c-Fos expression in the nucleus accumbens and the striatum using Fos-like-immunoreactivity(FLI). Male SD rats received acupuncture for 1 min after injection of cocaine hydrochloride(1 mg/kg, i.v.). The employed acupuncture point, Shenmen$(HT_7)$, has been clinically used to treat mental and psychosomatic disorders. Injections of cocaine produced a marked increase in locomotor activity and FLI in the nucleus accumbens and the striatum. Acupuncture at $HT_7$, but not at control points($PC_6,\;TE_4$ or tail), significantly attenuated cocaine-induced increase in locomotor activity and Fos-like immunoreactivity. These results demonstrated that reduction in locomotor activity by acupuncture may be reflected by reduction of postsynaptic neuronal activity in the nucleus accumbens and the striatum. Our results suggest that acupuncture may have a therapeutic effect on cocaine addiction.

• 생물정신의학
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• 제14권2호
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• pp.106-114
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• 2007

Objective : It is suggested that disturbance of dopaminergic system might be related to the possible mechanism of social phobia. The aim of this study was to investigate the possible association of DRD2 TaqI polymorphism and social phobia. Method : Fifty-one patients with social phobia and 200 comparison subjects were tested for DRD2 TaqI A polymorphism. The severity of social phobic symptoms was measured by self-report version of the Liebowitz Social Anxiety Scale(LSAS-SR) and Hamilton anxiety scale(HAM-A). Results : There was no signigicant difference in the genotype, allele frequency, A1 carrier frequency, and heterozygote frequency DRD2 TaqI A polymorphism between the social phobia patients and the control groups. However, we found significant decrease in somatic anxiety of the HAM-A in the patients having A2A2 homozygotes(p=0.014). In addition, patients having A1A2 heterozygotes showed more anxiety in two subscales (p=0.042 in anxiety, p=0.019 in performance) of the LSAS-SR. Conclusion : These results suggest that DRD2 A2 homozygote might have a protective role against somatic anxiety, and molecular heterosis of DRD2 TaqI A polymorphism might be related with more severe anxiety in social phobia.

• Animal cells and systems
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• 제4권1호
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• pp.71-76
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• 2000

The aim of this study was to investigate expression patterns of the prolactin (PRL) and c-fos genes by 17$\beta$-estradiol (17$\beta$-E) and stress in the mouse pituitary. In the pituitary, the levels of PRL mRNA were found high with some fluctuation at 30, 50, and 90 min whereas the levels of PRL mRNA were low at 120 min when ovariectomized female mice were injected with 17$\beta$-E or vehicle. PRL mRNA levels began to increase again at 4 h and remained high up to 24 h only in the 17$\beta$-E- treated mice. The overall changes in c-fos mRNA by 17$\beta$-E were very similar to those in PRL mRNA in the pituitary. Subsequent study revealed that these high initial levels of PRL and c-fos mRNAs were caused by stress during Injection, not by 17$\beta$-E, since vehicle injection alone into the ovariectomized mice could increase the levels of PRL and c-fos mRNAs. The stress-induced elevations of PRL and c-fos mRNAs were inhibited by bromocriptin, a dopamine agonist, suggesting that the dopaminergic system is involved in the action route of injection stress. In addition, the induced levels of c-fos mRNA by 17$\beta$-E and stress in the pituitary were very low compared with those in the uterus. The time course changes in c-fos mRNA level were different between the pituitary and uterus. Taken together, these data indicate that PRL and c-tos gene expression in the pituitary are regulated by 17$\beta$-E and stress in a parallel manner, supporting the notion that c-Fos plays a role in regulation of PRL gene expression.

• 한국산업정보학회논문지
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• 제28권2호
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• pp.31-45
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• 2023

본 연구는 유튜브 이용자의 사용 시간이 양적으로 증대하면서 나타나는 질적 단계와 경로에 주목하였다. 그리고 심리학과 신경과학의 이론을 적용하여 추천시스템의 개인화 알고리즘과 적극이용의 구간을 세분화하였고, 이론연구와 실증연구를 병행하였다. 이론연구에서 심리학과 신경과학의 관점으로 포그의 행동모델(FBM), 가변적 보상, 도파민 중독을 적용하였다. 포그의 행동모델(FBM)은 연관 콘텐츠 제시 기능인 개인화 추천 알고리즘이 트리거(계기)로서 쉬운 클릭을 유발하고, 가변적 보상은 검색하는 콘텐츠에 대한 예측불가능성으로 동기부여의 효과성을 높이며, 도파민 중독은 도파민 신경을 자극하면 지속적 적극적으로 콘텐츠를 소비하게 하는 것으로 요약된다. 본 연구는 개인화 추천 알고리즘과 적극이용 구간에서 콘텐츠의 이용 목적을 심리적 측면에서 처음이용, 재이용, 지속이용, 적극이용의 4단계로 구분하고, 경로를 분석하였다는 점에서 학문적 실무적 기여를 할 것으로 기대한다.

• Journal of Ginseng Research
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• 제47권4호
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• pp.552-560
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• 2023

Background: Ginseng Radix (Panax ginseng Meyer, Araliaceae) has been used medicinally to treat the brain and nervous system problems worldwide. Recent studies have revealed physiological effects that could potentially benefit cognitive performance or mood. The present study aimed to investigate the antidepressant effects of Korean red ginseng water extract (KGE) and its active component in an unpredictable chronic mild stress (UCMS)-induced animal model and elucidate the underlying mechanisms. Methods: The antidepressant potential of the UCMS model was evaluated using the sucrose preference test and open field tests. The behavioral findings were further corroborated by the assessment of neurotransmitters and their metabolites from the prefrontal cortex and hippocampus of rats. Three doses of KGE (50, 100, and 200 mg/kg) were orally administered during the experiment. Furthermore, the mechanism underlying the antidepressant-like action of KGE was examined by measuring the levels of brain-derived neurotrophic factor (BDNF)/CREB, nuclear factor erythroid 2-related factor 2 (Nrf2), and Kelch-like ECH-associated protein 1 (Keap1) proteins in the prefrontal cortex of UCMS-exposed rats. Results: KGE treatment normalized UCMS-induced depression-related behaviors. Neurotransmitter studies conducted after completing behavioral experiments demonstrated that KGE caused a reduction in the ratio of serotonin and dopamine, indicating a decrease in serotonin and dopamine turnover. Moreover, the expression of BDNF, Nrf2, Keap1 and AKT were markedly increased by KGE in the prefrontal cortex of depressed rats. Conclusion: Our results provide evidence that KGE and its constituents exert antidepressant effects that mediate the dopaminergic and serotonergic systems and expression of BDNF protein in an animal model.

• 동의생리병리학회지
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• 제18권3호
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• pp.767-773
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• 2004

Substantial evidence suggests that repeated injections of nicotine produce increase in locomotor activity and expression of the immediate-early gene, c-fos in the dopaminergic target areas. Herbal medicine as a therapeutic intervention has been widely used for the treatment of mental dysfunction. Many studies have shown that Cortex Phellodendris (CP) can affect the biochemical balance in the central nervous system. In order to investigate whether CP have an influence on their nicotine-induced behavioral sensitization, we examined the effect of CP on nicotine-induced locomotor activity and c-Fos expression in the striatum and nucleus accumbens utilizing the Fos-like immunohistochemistry (FLI). Male SD rats received CP (200㎎/㎏, i.p.) 30 min before repeated daily injections of nicotine (0.4㎎/㎏, s.c.) for 7 days. Rats were followed withdrawal for 3 days and one challenge for 1 day. System challenge with nicotine produced a much larger increase in locomotor activity and accumbal FLI. Pretreatment with CP significanly inhibited nicotine-induced locomotor activity and FLI in the striuatum and nucleus accumbens. These results demonstrated that reduction in locomotor activity by CP may be reflected by reduction of dopamine release and postsynaptic neuronal activity in the striatum and nucleus accumbens. Our results suggest that CP may have therapeutic effect on nicotine addiction. Supported by a fund (99-PJ9-PG1-002-0004).

• 대한핵의학회지
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• 제39권6호
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• pp.481-488
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• 2005

목적: 도파민운반체의 기능적 영상술은 도파민 신경계의 시냅스전 신경말단의 상태를 나타내 줄 수 있어, 기저신경절을 침범하는 파킨슨 병 등의 진단 및 중증도 판단에 이용될 수 있으며, 도파민운반체가 코카인이나 methamphetamine 등 의존성 약물의 목표 부위이므로 이러한 약물의 남용자의 평가에 이용될 수 있다. 본 연구는 한국에서 생산된 도파민운반체 영상용 방사성의약품을 사용한 뇌 SPECT영상을 이용하여 methamphetamine 남용자에서 나타나는 소견과 이의 임상적 의의를 알아보고자 하였다. 대상 및 방법: Methamphetamine 남용자 6명 (남용자군, 전부 남자, 평균연령: $32{\pm}6.8$) 및 정상대조군 4명(대조군, 남:여=3:1, 평균연령=$44.0{\pm}14.7$세)을 대상으로 하였다. 남용자군 6명 모두에서 뇌 MRI가 시행되었다. 남용자군에서는 정신과적 증상과 우울증 증상을 정량적으로 평가하였다. 도파민운반체 영상은 I-123 IPT 185 MBq을 정맥 주사한 후 2시간에 삼중헤드 감마카메라(Prism 3000, Picker, USA)를 이용하여 뇌 SPECT 영상을 얻었다. 정성적인 판독과 함께, 정량적 분석으로 기저신경절 부위에 관심영역을 그려 기저신경절의 방사능량을 구하였고, 배후 방사능량은 후두엽 부위에 관심영역을 그려 방사능량을 구하였다. 기저신경절과 배후 방사능량을 이용하여 기저신경절 도파민운반체 특이결합/비특이결합 비율(특이결합비) (기저신경절방사능량-배후방사능량/배후방사능량)을 구하였다. 각군의 도파민운반체 특이겹합비를 비교하였으며, 남용자군에서는 정신과적 증상(Brief Psychiatric Rating Scale: BPRS) 및 우울증 증상 정도(Hamilton Depression Rrating Scale : HAMD)와 도파민운반체 특이겹합비의 상관성을 알아보았다. 결과: 남용자군 6명 모두는 뇌 MRI상 특이 소견이 관찰되지 않았으나, 모든 환자는 정신과적 증상과 우울증 증상을 나타내었으며 BPRS 점수와 HAMD 점수는 서로 밀접한 상관성을 보여 주었다(r=1.0, p=0.005). 남용자군의 I-123 IPT 뇌 SPECT의 정성적분석에서 5명(83.3%)이 기저신경절의 전체적 섭취가 불균등하고 미측의 섭취가 감소되어 비정상으로 판독 되었으며, 1명은 정상으로 판독되었다. 남용자군은 대조군에 비하여 낮은 기저신경절 도파민운반체 특이겹합비를 나타내었다($2.38{\pm}0.20\;vs\;3.04{\pm}0.27$, p=0.000) 남용자군의 BPRS 점수와 HAMD 점수가 높을수록 낮은 기저신경절 특이겹합비를 나타내어 역의 상관관계를 보였다(r=-0.908, p=0.012, r=-0.924, p=0.009). 결론: I-123 IPT뇌 SPECT는 흑질-선조체 도파민신경계의 손상을 일으키는 중증의 methamphetamine 남용자의 평가에 이용될 수 있다고 생각된다.

• Journal of Pharmaceutical Investigation
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• 제32권2호
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• pp.127-133
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• 2002

Levosulpiride is the 1evo-enantiomer form of racemic sulpiride, a benzamide derivative selectively inhibiting dopaminergic $D_2$ receptors at the trigger zone both in the central nervous system and in the gastrointestinal tract. The purpose of the present study was to evaluate the bioequiva1ence of two levosulpiride tablets, Levopride (SK Pharmaceutical Co., Ltd.) and Levopid (Dae Won Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The levosulpiride release from the two levosulpiride tablets in vitro was tested using KP VII Apparatus II method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty eight normal male volunteers, $23.82{\pm}3.26$ years in age and $69.13{\pm}8.58$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 25 mg of levosulpiride was orally administered, blood was taken at predetermined time intervals and the concentrations of levosulpiride in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two levosulpiride tablets were very similar at all dissolution media. Besides, the pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t\;and\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two tablets based on the Levopride were -1.17%, 1.20% and -1.09%, respectively. There were no sequence effects between two tablets in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) $(e.g.,\;log(0.93){\sim}log(1.07)\;and\;log(0.90){\sim}log(1.14)\;for\;AUC_t\;and\;C_{max}$, respectively). The 90% confidence interval using untransformed data was within ${\pm}20%$ $(e.g.,\;-19.47{\sim}16.20\;for\;T_{max})$. All parameters met the criteria of KFDA guideline for bioequivalence, indicating that Levopid tablet is bioequivalent to Levopride tablet.

• 생물정신의학
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• 제5권1호
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• pp.83-94
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• 1998

Objectives : Phencyclidine(PCP) or PCP-like substances such as ketamine have been known to rekindle the cognitive dysfunction in schizophrenia. The aims of this study were to identify whether PCP-like substances can produce cognitive deficit in schizophrenia, to discuss relation with aging process, and finally to speculate underlying neurochemical mecha-nisms by various drug responses. Methods : In experiment I, radial maze tests were done in 24 Sprague-Dawley rats for 3 days to get baseline data. Being divided into 4 groups(6 rats respectively) of normal aged, normal adult controls, atropine-treated and ketamine-treated, the radial maze tests were repeated on every week for 6 weeks, and then the rats were sacrificed by intracardiac perfusion with phosphate-buffered 10% formaldehyde solution for histology. The brain specimen was stained with hematoxylin-eosin to count cells in the prefrontal cortex and hippocampus. In experiment II, radial maze tests were done for 48 rats before any drug treatment and only after ketamine administration. Thereafter, haloperidol, bromocriptine, clonidine, nimodipine, tacrine, valproic acid, naloxone and fluoxetine were intramuscularly injected on every other day in addition to ketamine. Radial maze tests were repeated on every week for 6 weeks, and then rats were prepared by the same procedure for histology. Results : 1) Reaction times of radial maze tests of atropine-treated rats were significantly prolonged than those of normal aged(p<0.05) or normal adult controls(p<0.05). Cell numbers of prefrontal cortex & hippocampus in ketamine-treated rats were significantly reduced than those in normal aged (p<0.05) or normal adult controls(p<0.005). 2) Reduced cell numbers by ketamine became significantly raised by tacrine administration in prefrontal cortex & hippocampus(p<0.05), while there were no significant changes on radial maze tests. Cell numbers also tended to be raised by nimodipine, fluoxetine and haloperidol administration. Conclusions : In conclusion, the visuospatial memory disorders in ketamine-induced psychotic rats might be partly asso-ciated with aging process. Furthermore, the responses to the various drugs suggested cholinergic system might have an important role in the neurochemical mechanism of the cognitive dysfunction in ketamine-induced psychosis. Otherwise, calcium metabolism as well as serotonergic and dopaminergic systems seemed to be possibly related.