scholarly journals Impact of amitriptyline on learning and memory

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.

2013 ◽  
Vol 750-752 ◽  
pp. 1533-1538
Author(s):  
Yan Chun Wang ◽  
Kuang Ren ◽  
Nan Shen ◽  
Xiao Dong Huang ◽  
Hong Yan Fan

We assessed the effectiveness and mechanism of action of schisandrin on modulation of learning and memory disorders in mice. Memory impairment was established in mice by intraperitoneal injection of pentobarbital sodium (20 mg/kg). Schisandrin (0.5, 1.0, 2.0g/kg) were administered by intragavage once daily for 14 consecutive days. The Morris water maze test was used to evaluate the ability of schisandrin to reduce phenobarbital-induced learning and memory impairment. The levels of superoxide dismutase (SOD) nitric oxide (NO) and catalase (CAT) were measured in brain tissue samples taken from the mice. Other biomarkers measured included expression of nuclear transcription factor-kappa-B (NF-κB) and brain-derived neurotrophic factor (BDNF) in the hippocampus CA1 region, which were determined by immunohistochemical analysis. On the fifth day of treatment, the mice in the pentobarbital sodium group performed worse on the Morris water maze test compared to untreated controls (P<0.01), which could be prolonged after schisandrin treatment (P<0.05 for="" low="" and="" intermediate="" dose="" groups="" analysis="" of="" brain="" tissues="" showed="" that="" compared="" with="" the="" control="" group="" no="" levels="" were="" increased="" sod="" cat="" activity="" decreased="" in="" pentobarbital="" sodium="" i="">P<0.01). After treatment with schisandrin, the NO levels were significantly decreased (P<0.01), while SOD and CAT activity increased (P<0.01). Immunohistochemistry analysis showed that, in phenobarbital only group, the protein expression of BDNF decreased, NF-κB increased compared to untreated controls, and schisandrin could reverse this trend (P<0.05 and="" i="">P<0.01, respectively). The results suggest that schisandrin is effective in improving the learning and memory deficiency induced by pentobarbital sodium, the mechanism of which may be related modulation of cellular response to oxidative stress.


2021 ◽  
Vol 19 ◽  
Author(s):  
Tingting Pi ◽  
Guangping Lang ◽  
Bo Liu ◽  
Jingshan Shi

Background: High methionine-diet (HMD) causes Alzheimer's disease (AD)-like symptoms. Previous studies have shown that Dendrobium nobile Lindle. alkaloids (DNLA) had potential benefits for AD. Object: Whether DNLA can improve AD-like symptoms induced by HMD is to be explored. Method: Mice were fed with 2% HMD diet for 11 weeks, the DNLA20 control group (20 mg/kg), DNLA10 group (10 mg/kg), and DNLA20 group (20 mg/kg) were administrated with DNLA for 3 months. Morris water maze test was used to detect learning and memory ability. Neuron damage was evaluated by HE and Nissl stainings. Levels of homocysteine (Hcy), beta-amyloid 1-42 (Aβ1-42), S-adenosine methionine (SAM), and S-adenosine homocysteine (SAH) were detected by ELISA. Immunofluorescence and western blotting (WB) were used to determine the expression of proteins. CPG island methylation. Results: Morris water maze test revealed that DNLA improved learning and memory dysfunction. HE, Nissl, and immunofluorescence stainings showed that DNLA alleviated neuron damage and reduced the 5-methylcytosine (5-mC), Aβ1-40, and Aβ1-42 levels. DNLA also decreased the levels of Hcy and Aβ1-42 in the serum, along with decreased SAM/SAH levels in the liver tissue. WB results showed that DNLA down-regulated the expression of the amyloid-precursor protein (APP), presenilin-1 (PS1), beta-secretase-1 (BACE1), DNA methyltransferase1 (DNMT1), Aβ1-40, and Aβ1-42 proteins. DNLA also up-regulated the expression of the protein of insulin-degrading enzyme (IDE), neprilysin (NEP), DNMT3a, and DNMT3b. Meanwhile, DNLA increased CPG island methylation levels of APP and BACE1 genes. Conclusions: DNLA alleviated AD-like symptoms induced by HMD via the DNA methylation pathway.


2013 ◽  
Vol 411-414 ◽  
pp. 3178-3180
Author(s):  
Li Hai Jin ◽  
Xing Yu Zhao ◽  
Wei Zhang ◽  
Wei Chen ◽  
Guo Qing Sun ◽  
...  

We assessed the effectiveness and mechanism of action of Soybean Isoflavones on learning and memory and Caspase-3 levels in the hippocampus of rats after Morris water maze (MWM test). Soybean Isoflavones (200,400 or 800 mg/kg/d) were administered by intragavage once daily for 14 consecutive days. The Morris water maze test was used to evaluate the ability of Soybean Isoflavones to increase learning and memory impairment. The levels of Caspase-3 in hippocampus of rats were detected by Westernblot after MWM test. Compared to untreated controls (P<0.01), MWM could be prolonged after Soybean Isoflavones treatment (P<0.05 for="" low="" and="" intermediate="" dose="" groups="" westernblot="" analysis="" showed="" that="" the="" protein="" expression="" of="" caspase-3="" was="" decreased="" in="" different="" concentration="" soybean="" isoflavones="" i="">P<0.05 and="" i="">P<0.01, respectively). The results suggest that Soybean Isoflavones is effective in improving the learning and memory in rats , the mechanism of which may be related Caspase ways.


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.


2011 ◽  
Vol 98 (3) ◽  
pp. 398-404 ◽  
Author(s):  
Oguz Mutlu ◽  
Güner Ulak ◽  
Ipek Komsuoglu Celikyurt ◽  
Füruzan Yıldız Akar ◽  
Faruk Erden

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Xin Wang ◽  
Yanhuan Miao ◽  
Jiawula Abulizi ◽  
Fu Li ◽  
Yuping Mo ◽  
...  

Objectives. To explore the alterations ofβ-amyloid (Aβ) and low density lipoprotein receptor-related protein-1 (LRP1) in APP/PS1 mice after electroacupuncture (EA) treatment and further to explore the mechanism.Methods. Forty 6-month-old APP/PS1 mice were randomly divided into a model group and an EA group, with twenty wild-type mice used as a normal control group. Mice in the EA group were treated with EA at GV 20 (băi huì) and bilateral KI 1 (yŏng quán) acupoints for 6 weeks. The Morris water maze was applied to assess the spatial memory in behavior. Immunohistochemistry (IHC), ELISA, Western blotting, and so forth were used to observe the expression of LRP1 and Aβ.Results. The Morris water maze test showed that, compared with the normal control group, the model group’s learning and memory capabilities were significantly decreased (P<0.05;P<0.01). The EA group was reversed (P<0.05;P<0.01). The hippocampal expression of Aβin the EA group was significantly decreased compared to the model group (P<0.01). The expression of LRP1 in the model group was significantly lower than that in the normal control group (P<0.01); the expression in the EA group was significantly higher than that in the model group (P<0.01).Conclusions. EA therapy can improve the learning and memory capabilities of APP/PS1 mice. The underlying mechanism may lie in the upregulation of an Aβtransport receptor and LRP1.


2012 ◽  
Vol 30 (4) ◽  
pp. 339-345 ◽  
Author(s):  
Guomin Li ◽  
Xuezhu Zhang ◽  
Haiyan Cheng ◽  
Xuemei Shang ◽  
Hui Xie ◽  
...  

Objectives To examine whether acupuncture could improve cognitive deficits and reduce the loss of neurons in mice models of ageing. Methods Male 7.5-month-old senescence-accelerated mouse prone 8 (SAMP8) and age-matched senescence-resistant inbred strains 1 (SAMR1) were divided into four groups (n=15 per group): SAMP8 acupuncture group (Pa), SAMP8 non-acupuncture point control group (Pn), SAMP8 control group (Pc) and SAMR1 normal control group (Rc). The behaviours were examined by the Morris water maze test and the neuron density in the hippocampus was estimated by the optical fractionator technique. Results The Morris water maze test demonstrated that the cognitive deficits of SAMP8 mice were improved by acupuncture treatment. Neuronal loss was found in hippocampal regions CA1 (−24%), CA3 (−18%) and DG (−28%) of Pc compared with Rc. The neuron number in hippocampal CA3 and DG of the Pa group was significantly increased by therapeutic acupuncture compared with the Pc group. Conclusions Acupuncture improved the cognitive impairment of middle-aged SAMP8 mice which could be attributed to the reduced neuron loss in hippocampal regions CA3 and DG. These results suggest that reducing neuron loss in the hippocampus by acupuncture is a potential therapeutic approach for the treatment of Alzheimer's disease and cognitive impairment diseases.


2020 ◽  
Author(s):  
Liu-Lin Xiong ◽  
Xiu-Juan Dong ◽  
Lu-Lu Xue ◽  
Jun-Jie Chen ◽  
Mohammed Al-hawwas ◽  
...  

Abstract Background: Suitable exercise can promote development of cognitive function and improve learning and memory ability of the hippocampus. Nevertheless, mechanisms that elicit these positive effects of exercise are yet needing to be elucidated. IGF2 is known to act as a potent memory and cognitive enhancer, whereas the mechanism by which IGF2 regulates cognitive function related to moderate treadmill exercise remained largely vague.Methods: In the study, rats were subjected to slight, moderate and high intensity treadmill training for 6 weeks. Then, Morris Water maze test was employed to investigate hippocampus-dependent spatial learning and memory ability in rats subjected to different intensity treadmill exercise. Subsequently, the gene chip and Gene Ontology were used for analysis to explore the expression level of IGF2. Furthermore, The TargetScan_7.1, miRDB, and microRNA.org. databases was used to predict the target gene of IGF2. Results: After Morris Water maze test, we found that middle intensity treadmill training could obviously enhance learning and memory function of rats. The qRT-PCR and western blot confirmed that the expression of IGF2 was significantly upregulated in hippocampus after moderate treadmill exercise. Through databases, miRNA-483 was screened and predicted as the target gene of IGF2. Moreover, silencing IGF2 inhibited the neurite growth in the hippocampus of rats, while, miRNA-483-inhibitor ameliorated the silencing IGF2 induced hippocampal neurons impairment to promote the neurite outgrowth.Conclusions: These findings suggested that the treadmill training could enhance the cognitive function, in which the underlying mechanism is involving in elevating the expression level of IGF2 and associated with downregulated miRNA-483. This therefore provide a reliable theoretical explanation on improving cognitive function induced by moderate exercise.


Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Akinori Higaki ◽  
Masaki Mogi ◽  
Jun Iwanami ◽  
Li-Juan Min ◽  
Harumi Kan-no ◽  
...  

Objective: Angiotensin (Ang) converting enzyme (ACE) 2/ Ang-(1-7)/Mas receptor axis has been considered as protective arm in the renin-angiotensin system and Ang-(1-7) is thought to interact with Ang II type 2 (AT 2 ) receptor according. Mas receptor is expressed highly in hippocampus and blood vessels in brain, but its actual function is still unclear. Thus, we examined the possible roles of Mas receptor in relation to the vascular cognitive impairment focusing on the interaction with AT 2 receptor. Design and Methods: Male 10-week-old C57BL6 mice (wild-type, WT), Mas1 receptor knockout mice (MasKO) and AT 2 /Mas1 receptor double knockout mice (DKO) were subjected to bilateral carotid artery stenosis (BCAS) surgery. After six weeks from the treatment, we evaluated their cognitive function with Y-maze test and the Morris water maze test. Results: The cerebral blood flow (CBF) in each BCAS group was significantly reduced compared to its sham-operated counterparts (WT; 31.5±0.6 vs 28.0±0.8, MasKO; 31.7±0.8 vs 27.7±0.8, DKO; 33.0±0.5 vs 29.1±0.7). The alternation behavior (%) was significantly reduced in WT mice with BCAS compared to sham mice (69.6±3.5 vs 57.9±2.1), but there was no significant difference in MasKO and DKO mice (MasKO; 64.1±2.5 vs 63.1±2.5, DKO; 67.6±2.1 vs 61.1±4.0) in Y maze test. In the Morris water maze test, the mean arrival time at platform at day 5 (sec) was significantly higher in WT-BCAS mice than WT-sham mice (Sham; 20.9±4.6 vs BCAS; 47.3±6.5). In contrast to the results in WT, there was no significant difference in MasKO mice (Sham; 32.8±8.5 vs BCAS; 34.5±7.3). DKO-sham mice showed significantly lower spatial learning ability compared with WT-sham mice (DKO; 77.4±11.9 vs WT; 20.9±4.6). The total cell count in dentate gyrus area was significantly lower in WT-BCAS compared to WT-sham (sham; 255.7±7.0 vs BCAS; 209.4±5.4), but there was no significant change in MasKO mice(sham; 256.5±2.5 vs BCAS; 233.2±16.4). We could not see significant difference in the number of DCX-positive cells and the expressions of proinflammatory cytokines such as IL-6, TNF-α and MCP-1in all mouse groups. Conclusion: Mas receptor deficiency seems to be beneficial in vascular dementia on condition that AT 2 receptor exists.


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