scholarly journals Effects of Long-Term Treatment with Atorvastatin and Rosuaastatin on Active Avoidance Test in Intact Rats

2013 ◽  
Vol 6 (1) ◽  
pp. 24-28
Author(s):  
Maria T. Georgieva-Kotetarova ◽  
Ivanka I. Kostadinova ◽  
Delian P. Delev

Summary Statins are widely used for treatment of hyperlipidemia. They have been shown to possess pleiotropic effects apart from their lipid-lowering activity - anti-inflammatory, immunomodulatory, and neuroprotective. Most studies suggest that statins can protect the brain against damage but it is not clear whether they improve cognitive function in patients without neuropathy. The aim of the present study was to investigate the effect of 3-month treatment with atorvastatin and rosuvastatin on learning and memory processes in rats without brain damage. Wistar rats were treated orally for 90 days with atorvastatin and rosuvastatin at a dose of 10 mg/kg b. w. in parallel with the vehicle-treated group. After that period, learning ability and memory retention was evaluated using an active avoidance test - automatic reflex conditioner (shuttle box). The learning session was carried out on 5 consecutive days. Memory retention test was performed on day 12. The following behavioral reactions were investigated: conditioned responses (avoidance), unconditioned responses (escapes), and intertrial crossings. We found increased number of conditioned responses in groups, treated with atorvastatin 10 mg/kg b.w., and with rosuvastatin 10 mg/kg b.w. during the learning session and on the memory retention test, as compared to the same-day control group. The atorvastatin-treated group showed an increased number of unconditioned responses on days 1 and 2, as compared to the control group. In the group treated with Rosuvastatin there was an increased number of escapes on days 1,2 and 4, as compared to the vehicle-treated group. Atorvastatin and rosuvastatin at a dose of 10 mg/kg b.w. improved processes of learning and memory retention after the 3-month treatment.


Folia Medica ◽  
2019 ◽  
Vol 61 (2) ◽  
pp. 258-265 ◽  
Author(s):  
Anita S. Mihaylova ◽  
Ilia D. Kostadinov ◽  
Nina D. Doncheva ◽  
Hristina I. Zlatanova ◽  
Delian P. Delev

Abstract Background: Parkinson’s disease (PD) is the second most common neurode-generative disease, usually detected by its motor symptoms. The non-motor symptoms, including cognitive deficits, have been of great interest to researchers in the last few decades. Aim: To assess the effect of pramipexole on learning and memory in naïve and haloperidol-challenged rats. Materials and methods: Male Wistar rats divided into 9 groups (n=8): naïve - saline, pramipexole 0.5; 1 and 3 mg/kg bw; Haloperidol groups - saline, haloperidol, haloperidol + pramipexole 0.5; 1 and 3 mg/kg bw. Two-way active avoidance test (TWAA) and activity cage were performed. The studied parameters were: number of conditioned and unconditioned responses, vertical and horizontal movements. Statistical analysis was done using SPSS 19. Results: The naïve experimental groups significantly increased the number of conditioned responses during the tests for short- and long-term memory, compared with the saline groups (p<0.05). During the short-memory test only the animals with the lowest dose of PMX significantly increased the number of unconditioned responses whereas during the long-term memory test all experimental groups increased the number of escapes in comparison with the saline groups (p<0.05). Challenge dose of haloperidol attenuates learning and memory in pramipexol treated rats. Only the highest dose of pramipexol showed significant increase in conditioned and unconditioned responses compared with the haloperidol group (p<0.05). Conclusion: Pramipexole improves learning and memory in naïve rats by enhancing dopaminergic neurotransmission. This is probably not the only mechanism involved. This is confirmed by the decrease in learning and memory ability in rats with haloperidol-challenge.



Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1205 ◽  
Author(s):  
Eunjin Sohn ◽  
Hye-Sun Lim ◽  
Yu Jin Kim ◽  
Bu-Yeo Kim ◽  
Joo-Hwan Kim ◽  
...  

We aimed to investigate the therapeutic effects of an Elaeagnus glabra f. oxyphylla (EGFO) ethanol extract in mice with scopolamine-induced memory dysfunction. Fifty male mice were randomly divided into a normal control group, a scopolamine-treated group, a scopolamine and EGFO extract-treated group, and a scopolamine and tacrine-treated group. EGFO (50 or 100 mg/kg/day) was received for 21 days. Step-through passive avoidance and Y-maze tests were performed to examine the effects of treatment on learning and memory impairments. Acetylcholine (Ach) levels and acetylcholinesterase (AchE) activity were measured via an enzyme-linked immunosorbent assay (ELISA). Levels of choline acetyltransferase (ChAT), nerve growth factor (NGF), cAMP response element-binding protein (CREB), and apoptosis-related protein expression were determined via Western blot analysis. EGFO pretreatment significantly attenuated scopolamine-induced memory impairments, relative to findings observed in the scopolamine-treated group. Levels of cholinergic factors in the brain tissues were markedly attenuated in the scopolamine-treated group. EGFO treatment also attenuated neural apoptosis in scopolamine-treated mice by decreasing the expression of apoptosis-related proteins such as Bax, Bcl2, cleaved caspase-3, and TUNEL staining. These results suggest that EGFO improves memory and cognition in a mouse model of memory impairment by restoring cholinergic and anti-apoptotic activity, possibly via activation of CREB/NGF signaling.



Author(s):  
Purabi Deka ◽  
Arun Kumar

Objective: The objective of the study was to investigate the memory improving activity of Triphala Churna hydro-methanolic fruit extract on learning and memory functions in Streptozotocin (I. C. V) induced dementia in rats by using morris water maze and elevated plus maze.Methods: A total of 42 albino wistar rats weighing 80-100 g were randomized into 7 equal groups as follows: Normal control group received normal saline (1 ml/kg p. o.) for 24 d, STZ treated group (3 mg/kg, i. c. v) were administered in two dosage regimen i.e. on first day and third day.), Standard group: Streptozotocin (3 mg/kg i. c. v)+Vitamin E (100 mg/kg/day p. o.) were administered for 21 d, Standard group: Streptozotocin (3 mg/kg i. c. v)+Rivastigmine (2 mg/kg/day p. o.) were administered for 21 d. The learning and memory-impaired rats were treated with Triphala Churna Formulation 1, Triphala Churna Formulation 2 and Triphala Churna Formulation 3 for 21 d (100 mg/kg p. o.). AchE activity, lipid peroxidation, superoxide dismutase, glutathione level of brain homogenate was estimated in Control/STZ (I. C. V)/Standard/Triphala Churna fruits extract treated rats.Results: Administration of Triphala Churna fruits extract significantly restored learning and memory impairment induced by STZ (I. C. V) in the elevated plus maze and morris water maze. Furthermore, in the TPLC F2 and TPLC F3 treated group brain AchE level was decreased (P≤0.01) as well as brain lipid peroxidation was also decreased (P≤0.001). Brain antioxidant enzymes such as glutathione level were increased (P≤0.001) in the TPLC1 and TPLC2 treated group when compared to the STZ treated group, TPLC F2 and TPLC F3 treated group showed significant (P≤0.001, P≤0.01) increase in superoxide dismutase level. Conclusion: Triphala Churna fruits extract has an improving effect on learning and memory impairment rats produced by Streptozotocin (I. C. V) and may have a useful effect in the treatment of dementia and Alzheimer's disease.



2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Yuan-Yuan Li ◽  
Nan-Qu Huang ◽  
Fei Feng ◽  
Ying Li ◽  
Xiu-Mei Luo ◽  
...  

Icaritin (ICT) is the main component in the traditional Chinese herb Epimedium, and it has been shown to have anti-Alzheimer’s disease (AD) effects, but its neuroprotective effects and the pharmacological mechanisms are unclear. In the present study, senescence-accelerated mouse prone 8 (SAMP8) mice were randomly divided into a model group and an ICT-treated group. Learning and memory abilities were detected by the Morris water maze assay, and the expression of amyloid beta protein (Aβ) and β-site APP cleavage enzyme 1 (BACE1) was determined by Western blotting and polymerase chain reaction (PCR). Histological changes in CA1 and CA3 were detected by hematoxylin-eosin staining (H&E staining), and the immunohistochemical analysis was used to detect the expression and localization of Bax and Bcl-2. The results showed that compared with the SAMP8 mice, the ICT-treated SAMP8 mice showed improvements in spatial learning and memory retention. In addition, the number of necrotic cells and the morphological changes in CA1 and CA3 areas were significantly alleviated in the group of ICT-treated SAMP8 mice, and the expression of BACE1, Aβ1-42 levels, and the Bax/Bcl-2 ratio in the hippocampus was obviously decreased in the ICT-treated group compared with the control group. The results demonstrated that ICT reduced BACE-1 levels, the contents of Aβ1-42, and the Bax/Bcl-2 ratio, suggesting that ICT might have potential therapeutic benefits by delaying or modifying the progression of AD.



Folia Medica ◽  
2013 ◽  
Vol 55 (2) ◽  
pp. 58-65 ◽  
Author(s):  
Maria T. Georgieva-Kotetarova ◽  
Ivanka I. Kostadinova

ABSTRACT During the past decade, evidence has emerged that statins have neuroprotective effects. AIM: The aim of this study was to investigate the effects of atorvastatin and rosuvastatin on learning and memory in rats with diazepam-induced amnesia. MATERIAL AND METHODS: Experiments were carried out on 48 white male Wistar rats, divided into 6 groups, each of 8 rats. The experimental animals were treated per os for 14 days with atorvastatin and rosuvastatin in doses of 10 mg/kg and 20 mg/kg body weight, respectively. To induce amnesia diazepam was administered intraperitoneally in a dose of 2.5 mg/kg bw. Cognitive skills of the animals were examined after the induction of amnesia with active avoidance test using autonomic reflex conditioner (shuttle box) and passive avoidance tests (step-through and step down) (Ugo Basile, Italy). The following parameters were assessed: number of conditioned responses (avoidances), number of unconditioned responses (escapes) and number of intertrial crossings in the active avoidance test; latency of reactions was measured in the passive avoidance tests. RESULTS: We found a significant increase of conditioned responses in atorvastatin treated animals (in a dose of 10 mg/kg bw) in active avoidance training. In the animals treated with rosuvastatin in both doses there was a statistically significant increase of unconditioned responses. In the step-through passive avoidance test there was significant improvement of short-term and long-term memory following administration of atorvastatin (10 mg/kg bw). Rosuvastatin (10 mg/kg bw) preserves long-term memory. In the step-down passive avoidance test, atorvastatin (10 mg/kg bw) and rosuvastatin (10 mg/kg bw and 20 mg/kg bw) preserve long-term memory. CONCLUSIONS: Atorvastatin (10 mg/kg bw) and rosuvastatin (10 mg/kg and 20 mg/kg bw) improve cognitive functions in rats with diazepam-induced amnesia and preserve longterm memory.



2015 ◽  
Vol 23 (1) ◽  
pp. 111-119 ◽  
Author(s):  
Koshi Ninomiya ◽  
Koichi Iwatsuki ◽  
Yu-ichiro Ohnishi ◽  
Toshika Ohkawa ◽  
Toshiki Yoshimine

OBJECT The intranasal delivery of bone marrow stromal cells (BMSCs) or mesenchymal stem cells to the injured brains of rodents has been previously reported. In this study, the authors investigated whether BMSCs migrate to spinal cord lesions through an intranasal route and whether the administration affected functional recovery. METHODS Forty Sprague-Dawley rats that were subjected to spinal cord injuries at the T7–8 level were divided into 5 groups (injured + intranasal BMSC–treated group, injured + intrathecal BMSC–treated group, injured-only group, injured + intranasal vehicle–treated group, and injured + intrathecal vehicle–treated group). The Basso-Beattie-Bresnahan (BBB) scale was used to assess hind limb motor functional recovery for 2 or 4 weeks. Intralesionally migrated BMSCs were examined histologically and counted at 2 and 4 weeks. To evaluate the neuroprotective and trophic effects of BMSCs, the relative volume of the lesion cavity was measured at 4 weeks. In addition, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels in the CSF were evaluated at 2 weeks. RESULTS Intranasally administered BMSCs were confirmed within spinal cord sections at both 2 and 4 weeks. The highest number, which was detected in the intrathecal BMSC–treated group at 2 weeks, was significantly higher than that in all the other groups. The BBB score of the intranasal BMSC–treated group showed statistically significant improvements by 1 week compared with the control group. However, in the final BBB scores, there was a statistically significant difference only between the intrathecal BMSC–treated group and the control group. The cavity ratios in the BMSC-treated groups were smaller than those of the control groups, but the authors did not find any significant differences in the NGF and BDNF levels in the CSF among the treatment and control groups. CONCLUSIONS BMSCs reached the injured spinal cord through the intranasal route and contributed to the recovery of hind limb motor function and lesion cavity reduction. However, the effects were not as significant as those seen in the intrathecal BMSC–treated group.



Open Medicine ◽  
2007 ◽  
Vol 2 (4) ◽  
pp. 430-446
Author(s):  
Darinka Dimitrova ◽  
Damianka Getova ◽  
Vesselin Belovezdov

AbstractCholinesterase inhibitors are currently used in the therapy of different kind of dementia to improve brain memory functions. The acetylcholinesterase inhibitor metrifonate was studied in naive rats and in rats with a model of sodium nitrite-induced hypoxia. One active avoidance test and in two passive avoidance tests were used. In the active avoidance test metrifonate increased the number of avoidances during the learning session only. In both passive avoidance tests, metrifonate prolonged latency differently during the learning session and in short-term or in long-term memory retention. Hypoxic rats showed lower numbers of avoidances in learning and memory retention sessions. Metrifonate increased the number of avoidances during the learning session for hypoxic rats. In the step-through passive avoidance test, metrifonate increased the latency of reactions in the learning session and in long-term memory retention tests. In the step-down passive avoidance test, the groups with hypoxia and metrifonate did not change the latency of reaction in the learning and long-term memory retention sessions, but increased the latency of reactions in the short-term memory retention test. Morphological data showed a significant impaired neuronal structure in a CA1 zone of the hippocampus in hypoxic rats and a tendency to preserving in rats treated with metrifonate. Our results suggest that metrifonate improves cognitive functions in naive and in hypoxic rats.



2000 ◽  
Vol 11 (8) ◽  
pp. 1479-1487 ◽  
Author(s):  
JÜRGEN WAGNER ◽  
CLAUDIUS DECHOW ◽  
CHRISTIAN MORATH ◽  
INGO LEHRKE ◽  
KERSTIN AMANN ◽  
...  

Abstract.In the reaction of kidneys to injury, cytokine-driven proliferation plays an important role and precedes the development of glomerulosclerosis. There is great interest in agents that may interfere with such proliferation. Therefore, a rat model of mesangioproliferative glomerulonephritis (induced by anti-Thy1.1) was studied, and the effects of all-trans-retinoic acid (all-trans-RA) and isotretinoin, powerful antiproliferative and anti-inflammatory substances, on glomerular damage and cell proliferation were examined. Vehicle-injected control rats were compared with rats treated with daily subcutaneous injections of 10 mg/kg body wt all-trans-RA or 40 mg/kg body wt isotretinoin (n= 9 to 11 per group), using either a pretreatment (days -2 through 8) or posttreatment (days +3 through +8) protocol,i.e., starting before or after the induction of anti-Thy1.1 nephritis, respectively. All-trans-RA prevented the BP increase evoked by anti-Thy1.1 (anti-Thy1.1/vehicle, 112.2 ± 4.8 mmHg; anti-Thy1.1/RA, 87.5 ± 2.5 mmHg;P< 0.001). Treatment with all-trans-RA or isotretinoin produced a 70% decrease in the urinary albumin excretion rate (P< 0.02). Periodic acid-Schiff staining of saline-perfused kidneys (day 8) revealed significantly fewer glomerular cells in RA-treated nephritic rats (anti-Thy1.1/vehicle, 97 ± 3.1 cells/glomerulus; anti-Thy1.1/RA, 80 ± 4.4;P< 0.02; control/vehicle, 69 ± 1.2). No difference was observed between all-trans-RA and isotretinoin treatment. The capillary occlusion scores were significantly lower for the anti-Thy1.1/RA-treated group (1.9 ± 0.1) than for the anti-Thy1.1/vehicle-treated group (2.9 ± 0.5,P< 0.001). In the anti-Thy1.1/vehicle-treated group, 11.9 ± 1.1 glomerular cells were proliferating cell nuclear antigen-positive; however, in the anti-Thy1.1/RA-treated group, only 5.3 ± 0.8 cells were proliferating cell nuclear antigen-positive (P< 0.002; control, 2.2 ± 0.2). Glomerular mitoses were reduced by 67% in the anti-Thy1.1/RA-treated group, compared with the anti-Thy1.1/control group (P< 0.002). Glomerular staining for platelet-derived growth factor B-chain was significantly reduced in anti-Thy1.1-treated nephritic rats in the presence of isotretinoin or all-trans-RA, compared with the vehicle-treated group (P< 0.001). It is concluded that all-trans-RA limits glomerular proliferation, glomerular lesions, and albuminuria in an established model of renal damage. The findings point to retinoids as potential novel modulators of glomerular injury.



2021 ◽  
Vol 5 (1) ◽  
pp. 009-015
Author(s):  
CC Mfem ◽  
SA Seriki

Background/aim: Amitriptyline belongs to class of known as tricycline antidepresant (TCA) that is being used to treat anxiety and depressive states. It may help improve mood and feelings of well-being, relieve anxiety and tension, help to improve sleep and increase energy level. The study investigated the effect of amitriptyline on learning and memory using eighteen (18) healthy Swiss mice of both sexes weighing 16 – 25 g. Method: The animals were divided into three (3) groups consisting of six (6) animals each. Group 1 served as the control group, Group 2 was administered with amitriptyline at a dose of 3 mg/kg body weight dissolved in 3 mls of distilled water, and used to test for learning, while Group three was also given similar administration like Group 2, but used to test for memory. All the animals were tested for learning and memory performance using Novel object recognition task and Morris water maze test. Results: The results obtained from the Novel object recognition task showed that there was a significant decrease (p < 0.05) in total object approach in acquisition trial of amitriptyline treated group when compared to the acquisition trial of the control group. There was a significant decrease (p < 0.05) in retention trial of amitriptyline group when compared to retention trial in the control group. There was a significant decrease (p < 0.05) in total duration exploring objects in acquisition trial of amitriptyline treated group when compared to the acquisition trial of the control group. There was a significant increase (p < 0.05) in total duration exploring objects in retention trial of amitriptyline treated group when compared to the retention trial of the control group. There was a significant decrease (p < 0.05) in the index of habituation of amitriptyline treated group when compared to the control group. The index of discrimination showed a significant increase (p < 0.05) in amitriptyline treated group when compared to the control group and a significant decrease (p < 0.05) in amitriptyline group when compared to the control group. In the Morris water maze test, Day 1 – 3 were for acquisition training, day 4 – 6 reversal training, day 7 the probe trial day and day 8 the visible platform day. During acquisition training in the Morris water maze test, there was no significant difference in Swim latencies in day 1 and 2. However in day 3, there was a significant increase (p < 0.05) in swim latency of group compared to control group and a significant decrease (p < 0.05) in swim latency of amitriptyline treated group compared to the control group. During reversal training in day 1, 2 and 3, there was no significant difference in swim latency among the three groups. Results for the retention quadrant in the probe trials showed a significant decrease (p < 0.01) in amitriptyline group when compared to the control group. Conclusion: Results suggest that amitriptyline impairs learning and memory functions.



2020 ◽  
Vol 52 (01) ◽  
pp. 35-36
Author(s):  
Melano Shavgulidze ◽  
Eka Chkhartishvili ◽  
Mariam Babilodze ◽  
Nino Rogava ◽  
Nargiz Nachkebia

INTRODUCTION Changes in some forms of motivational-emotional behavior, learning and memory are thought to be characteristic for major depressive disease. However, results existing until today about the character of changes in motivational-emotional and exploratory behavior as well as character of disorders in declarative memory, accompanying major depressive disease, are not unambiguous. Therefore, studying them in animal models of depression is very topical and important. METHODS Experiments were conducted on adult white wild rats (with 250-300 g weight). “Depressive” and “non- depressive” rats were selected according to the level of immobility in forced swim test. Rats with low level of immobility, “non-depressive” rats, constituted control group and rats with high level of immobility, “depressive” rats, constituted the experimental group (10 rats in each). Changes of motivational-emotional and exploratory behavior were studied in open field test. The changes of learning and memory were studied in the fear motivated one trial passive avoidance test considered as the declarative memory test. Experiments were carried out on “non-depressive”, control and “depressive”, experimental groups (10 rats in each). Obtained results were processed statistically by Student’s t-test. RESULTS Sharp decrease in locomotion was found in rats with high level of immobility. It was manifested in a significant decrease of the number of crossed squares. The quantitative indices of vertical activity, vertical standings, head risings, were also sharply decreased. Fear reaction was considerably increased in “depressive” rats, manifested in the significant decrease of the number of entering in the center of open field and grooming and sharp increase in defecation rate. Investigation of the changes of learning and memory in the passive avoidance test has shown that the latency of entering from the light into dark section of passive avoidance camera, in the learning session, was sharply increased in “depressive” rats. They revealed an impaired ability to evaluate the level of danger coming from the brightly illuminated open area and therefore they do not hurry to escape from the dangerous section. The difference between “depressive” and “non-depressive” rats was maintained even after 24 hours from receiving a painful stimulation. In particular, the animals of control group remember that they have received a painful stimulation in dark section during learning session and do not enter there during testing session, whereas the experimental animals with considerable delay but still enter in the dark section during testing session, therefore, they show significant impairment of declarative memory in passive avoidance task. CONCLUSIONS Locomotor and exploratory behavior are impaired and fear motivation is increased in the open field in “depressive” rats with high immobility and low level of monoamines content in the brain. Learning and memory in one of the tests of declarative memory, so called passive avoidance task, is disturbed.



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