• The Korean Journal of Physiology and Pharmacology
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• v.13 no.2
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• pp.71-78
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• 2009

(S)-Carbamic acid 2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-1-phenyl-ethyl ester hydrochloride (YKP1447) is a novel "atypical" antipsychotic drug which selectively binds to serotonin (5-$HT_{2A}$, Ki=0.61 nM, 5-$HT_{2C}$, Ki=20.7 nM) and dopamine ($D_2$, Ki=45.9 nM, $D_3$, Ki=42.1 nM) receptors with over $10\sim100$-fold selectivity over the various receptors which exist in the brain. In the behavioral studies using mice, YKP1447 antagonized the apomorphine-induced cage climbing ($ED_{50}$=0.93 mg/kg) and DOI-induced head twitch ($ED_{50}$=0.18 mg/kg) behavior. In the dextroamphetamine-induced hyperactivity and conditioned avoidance response (CAR) paradigm in rats, YKP1447 inhibited the hyperactivity induced by amphetamine ($ED_{50}$=0.54 mg/kg) and the avoidance response ($ED_{50}$=0.48 mg/kg); however, unlike other antipsychotic drugs, catalepsy was observed only at much higher dose ($ED_{50}$=68.6 mg/kg). Based on the CAR and catalepsy results, the therapeutic index (TI) value for YKP1447 is over 100 (i.p.). These results indicate that YKP1447 has an atypical profile and less undesirable side effects than currently available drugs.

• Korean Journal of Pharmacognosy
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• v.42 no.1
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• pp.32-37
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• 2011

The effects of herbal ethanol extract from Gynostemma pentaphyllum (GP extract) on chronic stress-induced anxiety in mice were investigated. The animals were treated with GP extracts (50 and 100 mg/kg/day, p.o.) for 21 days before exposure to electric footshock (EF; duration and interval 10 sec for 3 min, 2 mA) for chronic stress once a day. The ambulatory locomotor activity was reduced by chronic EF stress and it was recovered by 12.9-15.1% in GP extract-treated groups. The grip strength was also significantly decreased by chronic EF stress, however, the EF-stressed groups treated with GP extract increased grip strength from 13.9% to 56.8% compared to EF-stressed groups. In addition, the serum levels of corticosterone were significantly elevated by chronic EF stress to 197% of the control levels, which was reduced to 73.1% by treatment with GP extract (100 mg/kg). In contrast, the brain levels of dopamine and serotonin were reduced to 67.6% and 63.1% by chronic EF stress, which was recovered to 90% of the control levels by treatment with GP extract. These results indicate that GP extract shows the ameliorating effects on chronic EF stress-induced anxiety in mice and it can be developed as the promising anti-anxiety agent.

• Journal of Life Science
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• v.33 no.12
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• pp.995-1001
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• 2023

This study investigated the effects of three music genres (classical, new age, and rock) on the stress levels of six Jeju crossbred horses (Jeju horse × Thoroughbred) in a horse stable. The horses were exposed to the three genres for seven days, and their stress levels were measured by analyzing physiological markers, including neurotransmitter (cortisol, β-endorphin, dopamine, serotonin, and oxytocin) plasma levels and creatine phosphokinase (CPK) and aldolase serum levels. The neurotransmitter analysis showed significant differences in cortisol levels between classical and new age music exposure. Dopamine levels decreased significantly only with new age exposure. Although there were no significant differences in β-endorphin levels between the three genres, β-endorphin levels decreased with increasing classical and new age music playback times and increased with increasing rock music playback times. There were no significant differences in serotonin levels between the three genres. Oxytocin levels decreased significantly with exposure to classical and rock music. The CPK and aldolase analyses showed that CPK levels decreased significantly only with exposure to new age music and increased after playback ended, while aldolase levels decreased significantly with classical and new age music exposure and increased after playback ended. These findings suggest that classical music and new age are the optimal music genres for the psychological stability of Jeju crossbred horses. Playing back an appropriate music genre could be used to improve breeding and promote the welfare of Jeju crossbred horses.

• Korean Journal of Biological Psychiatry
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• v.6 no.2
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• pp.240-245
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• 1999

Object : This study was designed to evaluate the effects of olanzapine on the schedule-induced polydipsia(SIP) which is one of animal model of obsessive-compulsive disorder in rats. We administered olanzapine as a serotonin and dopamine blocking agent, fluoxetine as a selective serotonin reuptake inhibitor, and haloperidol for the dopamine antagonist to rats which showed schedule-induced polydipsic behavior. Methods : Spraque-Dawley rats weighing 200-250gm were individually housed and maintained and allowed free access to water. The rats were placed on a restricted diet. To induce polydipsia, rats were placed in the cage where a pellet dispenser automatically dispensed 90mg pellets on a fixed-time 60 seconds(FT-60s) feeding schedule over 150 minute test session per day. Water was available at all times in the cage. After 4 weeks of daily exposure to the FT 60s feeding schedule, experimental rats met a predetermined criterion for polydipsic behavior(greater than 3 times of water per session on average). 5 groups of rats were administered olanzapine(3mg/kg, i.p), olanzapine(10mg/kg, i.p), fluoxetine(5mg/kg, i.p.), haloperidol(0.1mg/kg, i.p.), and vehicle(1cc/kg, i.p.) for 3 weeks. The rats were tested once a week to access schedule induced polydipsic behavior. Water bottles were weighed before and after the 150-minute test session. The chronic effects of administration of experimental drugs on schedule induced polydipsic behavior were analyzed with ANOVA and Scheffe test as a posthoc comparison. In order to measure water consumption in non-polydipsic food-deprived rats, a separate group of rats(N=8) were individually housed and given a single bolus(14.5gm) of food per day which maintained them at their average body weight. Results and Conclusion : The results were as follows ; 1) After 4 weeks of scheduled feeding procedure, the experimental group showed significant differences than the bolus control in the amount of water consumption as compared with their average water intakes for 4 weeks. At the same periods, there were no differences between the experimental group and the bolus control in the body weight. 2) The fluoxetine group showed significant decrease in the amount of water intake over the 3 weeks of drug treatment as compared with their average amount of polydipsic water intakes. The olanzapine 3mg group showed significant decrease in the amount of water intake at 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. The olanzapine 10mg group showed significant decrease in the amount of water intake at 2nd and 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. However, the haloperidol group and the vehicle control group showed no changes of amounts of water intake for 3 weeks of treatment as compared with their average amount of polydipsic water intakes. 3) The fluoxetine group showed significantly lower amounts of water intake than the haloperidol group at 2nd weeks of drug treatment. And also the fluoxetine group showed significantly lower amounts of water intake than the haloperidol group and the vehicle control at 3rd weeks of drug treatment. The olanzapine 3mg group and the olanzapine 10mg group showed significantly lower amounts of water intake than the haloperidol group and the vehicle control at 3rd weeks of drug treatment. Above findings suggest that the fixed time feeding procedure for schedule-induced polydipsia as an animal model of obsessive compulsive disorder was effective to the evaluation of pharmacological challenge study. The authors assume that the serotonin hypothesis and the serotonin-dopamine interaction hypothesis are preferred to the dopamine hypothesis in the biological etiology of obsessive-compulsive disorder.

• Journal of Oriental Neuropsychiatry
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• v.12 no.1
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• pp.111-122
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• 2001

Objectives : This study aimed to evaluate the anti-stress effects of Guibi-tang and Yisiungyojae-dan on the contents of monoamines in the regional brain of mice immobilized stress. Methods : The experimental animals were immobilized in stress cylinder(height: 15cm, diameter: 3cm) for 15 minutes, and administered of Guibi-tang(6.0mg/10g) and Yishingyojae-dan(9.3mg/10g) water extracts for 7 days before stress. The monoamines contents were measured by HPLC method in various part(frontal cortex, hypothalamus, corpus striatum and hippocampus) of mice brain. Results: 1. In frontal cortex, the contents of norepinephrine were decreased with statistical significantly in Yishingyojae-dan administered group compared to control group. The contents of serotonin were decreased with statistical significance in all of the administered group compared to control group. 2. In hypothalamus, the contents of norepinephrine were decreased with statistical significantly in Yishingyojae-dan administered group compared to control group. The contents of serotonin were decreased with statistical significance in all of the administered group compared to control group. 3. In corpus striatum, the contents of dopamine were decreased with statistical significantly in Yishingyojae-dan administered group compared to control group. The contents of serotonin were decreased with statistical significance in all of the administered group compared to control group. 4. In hippocampus, the contents of serotonin decreased with statistical significantly in Yishingyojae-dan administered group compared to control group. Conclusions: This study shows that Guibitang and Yishingyojae-don are significantly effective on reducing and preventing stress in mice. In addition, Yishingyojae-dan is more clear effective than Guibi-tang on the monoamines change in the mice brain.

• Korean Journal of Biological Psychiatry
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• v.8 no.1
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• pp.116-122
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• 2001

Objectives : Schizophrenia manifests a variety of interindividual differences in therapeutic response to antipsychotics. This might be attributable to dopamine and serotonin receptors that a important target for various antipsychotics, and the $D_3$ receptor(DRD3) alleles they carry. The purpose of our study was to investigate whether the plasma levels of homovanillic acid(HVA) and 5-hydroxyindoleacetic acid(HIAA), and the polymorphism of DRD3 can be held as a predictor of treatment response in chronic schizophrenic patients. Methods : Therapeutic response for 116 korean schizophrenia patient treated during 48 weeks were assessed by PANSS used as the clinical symptom rating scales. The levels of concentration of HVA and 5-HIAA were examined by HPLC at baseline and at 48 weeks. We classified the polymorphism of DRD3 receptor using amplifying by polymerase chain reaction(PCR). Results : Neither concentrations of HVA and 5-HIAA nor genotype of dopamine 3 receptor were not significantly associated with the therapeutic response. But, the patients who has A1 alleles of DRD3 gene showed poor therapeutic responses. Conclusion : A1 allele of DRD3 gene is associated with poor prognosis of chronic schizophrenia.

• The Korean Journal of Nuclear Medicine
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• v.31 no.1
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• pp.9-18
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• 1997

The therapeutic efficacy of antipsychotic drugs is generally attributed to their ability to block dopamine $D_2$ receptors. Classical $D_2$ antagonists are not effective to treat negative symptoms and produce extrapyramidal side effects On the other hand, atypical antipsychotic agents ameliorate negative symptoms without producing extra-pyramidal side effects, and it is reported to be associated with blockade of serotonin $5-HT_2$ receptors. The purpose of this study was to evaluate the effect of risperidone on neuroreceptors in the rat brain by Quantitative autoradiography method. In acute treatment group, risperidone was injected into Peritoneal cavity of male Wistar rats with dose of 0, 0.1, 0.25, 0.5, 1.0 and 2.0mg/kg in each group(5/group), and they were decapitated after 2 hours. In chronic treatment group, risperidone was injected with dose of 0, 0.1, and 1mg/kg(I.P.) for 21 days and decapitated after 24 hours following last treatment. The effect of risperodone on the binding of [$^3H$]spiperone to $5-HT_2$ and $D_2$ receptors were analysed in 4 discrete regions of the striatum, nucleus accumbens, and frontal cortex by quantitative autoradiography Acute treatment with risperidone reduced cortical $5-HT_2$ specific [$^3H$]spiperone binding to 32% of vehicle-treated control. Subcortical $5-HT_2$ specific [$^3H$]spiperone binding was not affected at all dose groups whereas a significant reduction (57%) in $D_2$ specific [$^3H$]spiperone binding was observed in risperidone treated group at doses of 1-2mg/kg. Chronic treatment with risperidone produced a decrease in the maximal number of cortical $5-HT_2$ receptors to 51% and 46% of control in 0.1mg/kg & 1mg/kg treated group respectively. In conclusion, risperidone is a cortical serotonin receptor antagonist with relatively weak antagonistic action on dopamine receptors. These effects oil neuroreceptors may explain the therapeutic effect of risperidone as a atypical antipsychotic agents.

• Korean Journal of Biological Psychiatry
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• v.11 no.1
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• pp.14-25
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• 2004

The current understanding of the mechanisms of pharmacotherapy for depression is characterized by an emphasis on increasing synaptic availability of serotonin, noradrenaline, and possibly dopamine, while minimizing side effects. The acute effects of current available effective antidepressants include blocking selective serotonin or noradrenaline reuptake, alpha2 autoreceptors or monoamine oxidase. Although efficacious, current treatments often produce partial or limited symptomatic improvement rather than remission. While current pharmacotherapies target monoaminergic systems, distinct neurobiological underpinnings and other systems are likely involved in the pathogenesis of depression. Recently, several promising hypotheses of depression and antidepressant action have been formulated. These hypotheses are largely based on dsyregulation of neural plasticity, CREB, BDNF, corticotropin-releasing factor, glucocorticoid, hypothalamic-pituitary adrenal axis and cytokines. Based on these new theories and hypotheses of depression, a number of new and novel agents, including corticotropin-releasing factor antagonists, antiglucocorticoids, and substance P antagonists show a considerable promise for refining treatment options for depression. In this article, the current available pharmacotherapies, current understanding of neurobiology and pathogenesis of depression and new and promising directions in pharmacological research on depression will be discussed.

• Korean Journal of Biological Psychiatry
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• v.27 no.2
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• pp.58-63
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• 2020

Depressive disorder is a very common disease, clinical manifestations vary, and the mechanism is not clear. Therefore, a pharmacotherapy is very important to achieve sufficient therapeutic effect, but the choice of drug is not easy due to the occurrence of side effects of treatment and confusion with clinical features. It is easy to overlook the side effects of weight gain with antidepressants compared with antipsychotics, but they are frequently observed in clinical settings. The first-generation antidepressants have higher weight gains than selective serotonin reuptake inhibitors. Serotonin norepinephrine reuptake inhibitors are observed to have less weight gain, and dopamine norepinephrine reuptake inhibitors have weight loss effect due to decreased appetite. Mirtazapine, an atypical antidepressant, has a strong histamine H1 blockade, and gains weight gain from short-term use. The effects of desvenlafaxine, vortioxetine, and agomelatin on weight, which have recently been increasing in use, have not been largely identified. For better compliance, studies on weight gain due to the use of antidepressants are needed.

• Journal of Applied Biological Chemistry
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• v.61 no.4
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• pp.341-349
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• 2018

The aim of this study was to evaluate autophagy-enhancing and neuroprotective effects of Wonji-Gobon mixture (WGM), a traditional Chinese prescription medication, in Parkinson's disease (PD) mouse models. Our investigation found that WGM increased the expression of both Beclin1 and LC3b-II proteins as measured with western blot in the BV2 cell line; both proteins play a role in autophagy. WGM also increased the autophagy expression as measured by fluorescence-activated cell-sorting analysis in the BV2 cell line. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD models, WGM significantly increased the amount of dopamine in a striatum-substantia nigra suspension, produced notable results in the forced swim test, and increased serotonin as measured by high-performance liquid chromatography analysis; these results are indicative of neuroprotective effects. In summary, our findings indicate that WGM treatment has neuroprotective effects that are partially mediated by autophagy enhancement.