• Biomolecules & Therapeutics
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• v.16 no.4
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• pp.320-327
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• 2008

Several lines of evidence indicate that adenosine $A_{2A}$ agonist disrupts spatial working memory. However, it is unclear which stages of learning and memory are affected by the stimulation of adenosine $A_{2A}$ receptor. To clarify these points, we employed CV-1808 as adenosine $A_{2A}$ agonist and investigated its effects on acquisition, consolidation, and retrieval phases of learning and memory using passive avoidance and the Morris water maze tasks. During the acquisition phase, CV-1808 (2-phenylaminoadenosine, 1 and 2 mg/kg, i.p.) decreased the latency time in passive avoidance task and the mean savings in the Morris water maze task, respectively. During the consolidation and retrieval phase tests, CV-1808 did not exhibited any effects on latency time in passive avoidance task and the mean savings in the Morris water maze task. These results suggest that CV-1808 as an adenosine $A_{2A}$ agonist impairs memory acquisition but not consolidation or retrieval.

• Archives of Pharmacal Research
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• v.24 no.3
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• pp.234-239
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• 2001

Three types of learning and memory tests (Morris water maze, active and passive avoidance) were performed in rats following intracerebroventricular infusion of ethylcholine aziridium (AF64A). In Morris water maze, AF64A-treated rats showed the delayed latencies to find the platform iron 6th day after the infusion. In pretrained rats, AF64A caused the significant delay of latency at 7th days but not 8th day. In the active avoidance for the pretrained rats, the escape latency was significantly delayed in AF64A-treatment. The percentages of avoidance in AF64A-treated rats were less increased than those in the control. Especially, the percentage of no response in the AF64A-treated rats was markedly increased in the first half trials. In the passive avoidance, AF64A-treated rats shortened the latency 1.5 h after the electronic shock, but not 24 h. AF64A also caused the pretrained rats to shorten the latency 7th day after the infusion, but not 8th day. These results indicate that AF64A might impair the learning and memory. However, these results indicate that the disturbed memory by AF64A might rapidly recover after the first retrain. Furthermore, these results suggest that AF64A may be a useful agent for the animal model of learning for Spatial cognition .

• Journal of Oriental Neuropsychiatry
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• v.9 no.2
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• pp.19-35
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• 1998

Some oriental medicine turned out to have a significant clinical effect on the cure for dementia. Therefore, thorough scientific tests for physiological effect of oriental medicne are needed. This study is aimed at doing experimental studies on the effects of two medicines, Jowiseungcheongtang and hyungbangjihwangtang, on the cure for dementia.For the demonstration of the effect of the two medicines on aged rats, we perfomed a radial arm medicines on aged rats, water maze task, known for their proper learning paradigm for behavior.Previous studies on aging and dementia show that aged rats displayed significant impariments in the learning of the radial arm maze task compared with younger rats. As in experiment 1, we found that the learning of the radial arm maze task compared with younger rats. As in experiment 1, we found that the learning deficits aged rats exhibit in radial arm maze task were improved with the application of each medicine. The resutls suggest that these two medicine can be effective to patients whose working or shortterm memory is impaired. In experiment 2 we studied the effect of the two medicines on the deficit of the aged rats with the Morris water maze task known for measuring long-tern memory. We did not find significant results between the performance of the ages rats and the younger ones. Considered the different results previous studies have reported, more thorough studies are needed to investigate the effect of the medicines on long-term memory.In conclusion, the results we found in experiment 1 and 2 suggest that Jowisengcheongtang and hyungbangjihwangtang can have useful effects for the cure of age-related memory (especially for short-term memory)deficits. Recent interests in dementia urges researchers concerned to explore the effect of oriental medicine on the disease. As there have been relatively few behavioral or scientific studies on dementia using oriental medicine to date, further studies are expected are expected to continue to elucidate 'what the wisdom of the oriental medicine tells about dementia'.

• Journal of Oriental Neuropsychiatry
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• v.22 no.2
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• pp.85-105
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• 2011

Objectives : The purpose of this study was to characterize the neuroprotective effects and anxiolytic-like effects of Gongjin-dan and Polygala japonica, Polygala tenuifolia, Acorus gramineus mixed pills(G.J.D-P.P.A.). Methods : The neuroprotective effects of G.J.D-P.P.A. determined by the passive avoidance and Y-maze tasks and Morris water maze task, and the anxiolytic-like effects of the G.J.D-P.P.A. using an elevated plus-maze(EPM) in mice. Results : Drug-induced amnesia was induced by treating animals with scopolamine(1 mg/kg, i.p.). A single G.J.D-P.P.A.(400 and 800 mg/kg) administration significantly enhanced cognitive function and attenuated scopolamine-induced cognitive impairments as determined by the passive avoidance and Y-maze tasks(P < 0.05) and also reduced escape-latency on the Morris water maze task(P < 0.05). The administration of GJD-PPA(400 and 800 mg/kg) significantly increased the percentage of time spent in open arms and entries into the open arms of the EPM compared with saline-treated control group(P < 0.05). Moreover, there were no changes in the locomotor activity and myorelaxant effects in any group compared with saline-treated control group. Conclusions : These results suggest that GJD-PPA dramatically possesses the anti-amnestic and cognitive-enhancing activities related to the memory processes, and promotes the anxiolytic-like activity in mice.

• The Journal of Korean Medicine
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• v.29 no.5
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• pp.67-76
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• 2008

Objectives : Amnesia is theloss or impairment of memory, caused by physical injury, disease, drugs, or emotional trauma. Recently, the average life span is increasing, while at the same time, the incidence of dementia-like diseases in conjunction with amnesia are also increasing. Therefore learning and memory are very important issues in modern society. Ancient Korean physicians used several herbs to treat dementia and these herbal effects were described in Korean herbal books. Among them are some reports on several cognitive-enhancing herbs which have since been shown to improve dementia in recent pharmacological studies, such as Panax ginseng; however, the facilitatory effects of many Korean cognitive-enhancing herbs on learning and memory are limited. Learning and memory are essential requirements for every living organism in order to cope with environmental demands; cholinergic systems are known to be involved in learning and memory. Methods : In this study, the effects of Acori graminei rhizoma (AGR, 石菖蒲) on learning and memory were investigated by Morris water maze, eight-arm radial maze, and the effects on the central cholinergic system of rats injected with scopolamine. Results : In the water maze, the experimental animals were trained to find a platform in a fixed position for 6 days and then received a 60 sec probe trial in which the platform was removed from the pool on the 7th day. In the eight-arm radial maze, the animals were tested four times per day for 6 days. Scopolamine impaired performance of the maze tests and reduced activity of acetylcholinesterase (AchE) in the hippocampus, which is a marker for the central cholinergic system. There were significant reversals from the scopolamine-induced deficits on learning and memory in these tests, through daily administrations of AGR (100 mg/kg, p.o.) over 14 consecutive days. These treatments also reduced the loss of cholinergic activity in the hippocampus induced by scopolamine. Conclusions : These results demonstrated that AGR ameliorated learning and memory deficits by affecting the central acetylcholine system.

• Journal of Ginseng Research
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• v.18 no.1
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• pp.32-38
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• 1994

Male rats aged 15 months, which had been over-trained with 12 arm radial maze up to the criterion of 1 or 2 errors an average per trial, were divided into two groups and 7 months after the over-training and were studied the effect of red ginseng trial saponin fraction (PT) on the spatial memory function. The rats which could be improved the performance of 9.75$\pm$1.26 (within 185$\pm$8.2 1 sec) were classified into "normal group" (n=4) and the ones, which showed R-maze performance of 7.0$\pm$2.87 within 300 sec, "deteriorated memory group" (n=5). PT was dissolved in distilled water and injected into the deteriorated memory group intraperitoneally at 30 min before R-maze for 3 consecutive days. The injected amount of PT on the 1st day was 10mg/rat, 1mg/rat both on the 2nd the 3rd day. As results, the performance was restored to 9.4$\pm$2.0 after stopping ginseng administration, although the lower performance values (1.4$\pm$0.89, 2.8$\pm$0.83, 3.8$\pm$0.84, respectively) were exerted during the three days of PT administration than before PT administration (7.0$\pm$2.87) since 1 day after administratitan of PT. The restored performance values were continuously maintained up to the level of the "normal group". However, any lower performance values were not observed when PT was administered via intraperitoneal route to the normal group in about of 2 mg/rat except 10mg1ra1. The number of errors when the foods in arms were put at only 6 places was clearly reduced during the 9 days of consecutive administration of PT as compared with untreated control. These results indicated that PT administration may enhance their cognitive function after a long lapse of time not only in the memory deteriorated rats but also in normal ones. The reason exerted lower performance values during PT administration in this paper was discussed as compared with the results of T-maze behavior of another 3-month-aged rats. of another 3-month-aged rats.

• Physical Therapy Korea
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• v.15 no.4
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• pp.50-58
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• 2008

The purpose of this study was to investigate the effects of the task-oriented training according to the application time with the change of motor and cognition function. Focal ischemic brain injury was produced in Sprague-Dawley rats (20 rats, $250{\pm}50$ g) through middle cerebral artery occlusion (MCAo). Before MCAo induction, all rats were trained in treadmill training and Morris water maze training for 1 week. Then they were randomly divided into groups: Group I : MCAo induction ($n_1$=5), Grop II: the application for simple treadmill task training after. MCAo induction ($n_2$=5). Group III: the application for Morris water maze cognitive task training after MCAo induction ($n_3$=5). Group IV: the application for progressive treadmill task training and Morris water maze cognitive task training after MCAo induction ($n_4$=5). Modified limb placing tests (MLPTs) and motor tests (MTs) were performed to test motor function and then Morris water maze acquisition test (MWMAT) and Morris water maze retention test (MWMRT) were performed to test cognitive function. For MTs, there were significant interactions among the groups with the time (p<.001). Group IV showed the steeper increasing pattern than those in other Groups on the 7th and 14th day. For MLPTs, there were significant interactions among the groups with the time (p<.001). The scores in Group III. IV had showed the more decreasing pattern than those in Group I, II since the 7th day and 14th day. For MWMAT, there were significant interactions among the groups with the time (p<.001). Group II found the Quadrant circular platform showed the steeper decreasing pattern than that in Group I on the 9th, 10th, 11th and 12th day. Group III. IV found the quadrant circular platform showed the slower decreasing pattern than that in Group I, II, For MWMRT, there were significant differences among the four groups (p<.001). The time to dwell on quadrant circular platform in Group IV on the 13th day was the longest compared with other groups. These results suggested that the combined task training was very effective to improve the motor and cognition function for the rats affected on their focal ischemic brain injury.

• Journal of Oriental Neuropsychiatry
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• v.15 no.1
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• pp.43-64
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• 2004

The aim of this study was to evaluate the effects of Jowiseungcheongtang compared with St. John's wort in the chronic mild stress(CMS) animal model of depression. Wistar rats were used for this study. The subjects were divided into 4 groups (Naive group: without CMS procedure, CMS-vehicle: water was administered during CMS procedure, CMS-Jowiseungcheongtang: Jowiseungcheongtang was administered after 5 weeks of CMS procedure, CMS-St. John's wort: St. John's wort was administered after 5 weeks of CMS procedure) During 9 weeks of CMS procedure, The change of the consumption of sucrose and the changes of weights were measured. After CMS procedure, Morris water maze test, open field test, elevated plus maze test and Western blotting were measured. The results were as follows. 1. The consumption of sucrose solution was significantly reversed in Jowiseungcheongtang group and relatively reversed in St. John's Wort group at 7 week. 2. In open field test, Neither Jowiseungcheongtang nor St. John's wort group showed statistically significant change of exploratory activity. In EPM test, St. John's Wort group showed significant decrease of total arm entry in comparison with Naive group. And Jowiseungcheongtang group was showed no significant change. 3. In Morris water maze test, St. John's Wort group showed significant increase in escape latency of the last Morris water maze trial. And in water maze probe test, there was no significant change. 4. St. John's Wort group showed relative increase in LP1 division of 5HT1A receptor compared with Naive group. Both St. John's Wort and Jowiseungcheongtang group showed relative increase in P2 division of GluRl compared with Naive group. These results suggest that Jowiseungcheongtang is as effective as St. John's Wort in the treatment of depression.

• The Journal of Pediatrics of Korean Medicine
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• v.14 no.1
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• pp.9-38
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• 2000

It has been widely said in Korea that early administrations of Cervi cornu parvum (deer antler) to febrile infants affect brain functions. Traditional Oriental Medicine states that the head is easily affected by fever and only an excess of heat causes headaches. Traditional Oriental Medicine also states that Cervi cornu parvum cannot be used in febrile conditions. With the aim of investigating different febrile response to LPS, experiments using intravenous injection of LPS have been carried out on Cervi comu parvum(CCP) and Soahbohyul - tang combined with Cervi comu parvum(SB-CCP) administered rabbits. Experiments were also conducted to evaluate the effects of early administration of CCP on learning and memory in 3 week old rats with LPS fever. These were evaluated by using the Morris water maze and the radial arm maze. Changes in body weight were also observed during this period. The results of these experiments are as follows. 1. In the experiments with febrile rabbits, the CCP and SB-CCP administered group showed statistically significant reductions of fever (p<0.05). 2. In the experiments with febrile rabbits, CCP and SB-CCP administered rabbits resulted in the tendency of lower body temperatures and shorter fever periods than the control group. 3. There were no differences of mean body weight and fever patterns among the 4 groups in the experiments on young rats with LPS fever. 4. There was no statistical difference of mean response latencies among the rats in Group I (DDW administered), GroupIII (CCP administered), and groupIV (SB-CCP administered) in the Morris water maze. However, Group Ⅱ (the scopolamine administered group) showed delayed latencies on the second day of the first session (p<0.05), and the second and third day of the second session (p< 0.05). 5. There were no statistical differences of mean response latencies among the rats in Group I, III and Ⅳ in the radial arm maze, but Group Ⅱ showed delayed latencies on the first and third day of the first session (p<0.05). 6. There was no influence from the administration of CCP and SB-CCP on the general behavior of the rats in Irwin´s test. These results suggest that Cervi cornu parvum and Soahbohyul - tang combined with Cervi comu parvum have anti-pyretic actions on LPS fever. The results also suggest that these drugs have no influence on learning and memory in young rats with LPS fever in the Morris water maze and the radial arm maze.

• Journal of Ginseng Research
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• v.38 no.1
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• pp.1-7
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• 2014

Background: Although ginsenosides such as Rg1, Rb1 and Rg3 have shown promise as potential nutraceuticals for cognitive impairment, their use has been limited due to high production cost and low potency. In particular, the process of extracting pure Rg3 from ginseng is laborious and expensive. Methods: We described the methods in preparing ginseol k-g3, an Rg3-enriched fraction, and evaluated its effects on scopolamine-induced memory impairment in mice. Results: Ginseol k-g3 (25-200 mg/kg) significantly reversed scopolamine-induced cognitive impairment in the passive avoidance, but not in Y-maze testing. Ginseol k-g3 (50 and 200 mg/kg) improved escape latency in training trials and increased swimming times within the target zone of the Morris water maze. The effect of ginseol k-g3 on the water maze task was more potent than that of Rg3 or Red ginseng. Acute or subchronic (6 d) treatment of ginseol k-g3 did not alter normal locomotor activity of mice in an open field. Ginseol k-g3 did not inhibit acetylcholinesterase activity, unlike donezepil, an acetylcholinesterase inhibitor. Rg3 enrichment through the ginseol k-g3 fraction enhanced the efficacy of Rg3 in scopolamine-induced memory impairment in mice as demonstrated in the Morris water maze task. Conclusion: The effects of ginseol k-g3 in ameliorating scopolamine-induced memory impairment in the passive avoidance and Morris water maze tests indicate its specific influence on reference or long-term memory. The mechanism underlying the reversal of scopolamine-induced amnesia by ginseol k-g3 is not yet known, but is not related to anticholinesterase-like activity.