• Biomolecules & Therapeutics
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• v.20 no.2
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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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• v.19 no.1
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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.

• Korean Journal of Biological Psychiatry
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• v.14 no.2
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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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• v.4 no.1
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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.

• Journal of Korea Society of Industrial Information Systems
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• v.28 no.2
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• pp.31-45
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• 2023

This study deals with exploring qualitative steps and paths that appear as YouTube users' usage time increases quantitatively. For the study, I applied theories from psychology and neuroscience, subdivided the interval between the personalization algorithm of the recommendation system, and active use and analyzed the relationship between variables in this process. According to the theory behavioral model theory (FBM), variable reward, and dopamine addiction were applied. Personalization algorithms easy clicks as triggers according to associated content presentation functions in behavioral model theory (FBM). Variable rewards increase motivational effectiveness with unpredictability of the content you search, and dopamine nation is summarized as stimulating the dopaminergic nerve to continuously and actively consume content. This study is expected to make an academic and practical contribution in that it divides the purpose of use of content in the personalization algorithm and active use section into four stages from a psychological perspective: first use, reuse, continuous use, and active use, and analyzes the path.

• Journal of Ginseng Research
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• v.47 no.4
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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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.3
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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).

• The Korean Journal of Nuclear Medicine
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• v.39 no.6
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• pp.481-488
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• 2005

Purpose: Functional imaging of dopamine transporter (DAT) defines integrity of the dopaminergic system, and DAT is the target site of drugs of abuse such as cocaine and methamphetamine. Functional imaging the DAT may be a sensitive and selective indicator of neurotoxic change by the drug. The aim of the present study is to evaluate the clinical implications of qualitative/quantitative analyses of dopamine transporter imaging in methamphetamine abusers. Materials and Methods: Six detoxified methamphetamine abusers (abuser group) and 4 volunteers (control group) were enrolled in this study. Brain MRI was performed in all of abuser group. Abuser group underwent psychiatric and depression assessment using brief psychiatric rating scale (BPRS) and Hamilton depression rating scale (HAMD), respectively. All of the subjects underwent I-123 IPT SPECT (IPT SPECT). IPT SPECT image was analysed with visual qualitative method and quantitative method using basal ganglia dopamine transporter (DAT) specific/non-specific binding ratio (SBR). Comparison of DAT SBR between abuser and control groups was performed. We also performed correlation tests between psychiatric and depression assessment results and DAT SBR in abuser group. Results: All of abuser group showed normal MRI finding, but had residual psychiatric and depressive symptoms, and psychiatric and depressive symptom scores were exactly correlated (r=1.0, p=0.005) each other. Five of them showed abnormal finding on qualitative visual I-123 IPT SPECT Abuser group had lower basal ganglia DAT SBR than that of control ($2.38{\pm}0.20\;vs\;3.04{\pm}0.27$, p=0.000). Psychiatric and depressive symptoms were negatively well correlated with basal ganglia DAT SBR (r=-0.908, p=0.012, r=-0.924, p=0.009). Conclusion: These results suggest that dopamine transporter imaging using I-123 IPT SPECT may be used to evaluate dopaminergic system of the basal ganglia and the clinical status in methamphetamine abusers.

• Journal of Pharmaceutical Investigation
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• v.32 no.2
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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.

• Korean Journal of Biological Psychiatry
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• v.5 no.1
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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.