27 research outputs found
Effect of concomitant administration of three different antidepressants with vitamin B6 on depression and obsessive compulsive disorder in mice models
No full textVitamin B6 is a cofactor of various enzymes influencing numerous neurotransmitters in the brain such as norepinephrin, and serotonin. Since these neurotransmitters influence mood, the aim the present work to evaluate the effect of vitamin B6 on depression and obsessive compulsive behavior when coadministred with clomipramine, fluoxetine, or venlafaxine. Male mice weighing 25-30 g were used. The immobility time and latency to immobility was measured in the forced swimming test as a model of despair and the number of marbles buried (MB) in an open field was used as the model of obsessive compulsive behavior in mice. Vitamin B6 (100 mg/kg, i.p.) was injected to animals for six days and on the last day antidepressants were also administered and the tests took place with 30 min intervals. Immobility was reduced in vitamin B6 + clomipramine (141 ± 15 s) or venlafaxine (116 ± 15 s) but it was not significant comparing with the drugs alone. No beneficial response was seen in co-administration of vitamin B6 with fluoxetine compared to fluoxetine alone. Fluoxetine also increased the latency to first immobility. Vitamin B6 + clomipramine or venlafaxine reduced the MB behaviour by 77 ± 12% and 83 ± 7% respectively, while using them alone was less effective. Fluoxetine was very effective in reducing MB behaviour (95 ± 3.4%) thus using vitamin B6 concomitantly was not useful. Therefore vitamin B6 as a harmless agent could be suggested in depression and particularly in obsessive compulsive disorder as an adjuvant for better drug response
Alteration of ADP-ribosylation in aging rat brain astrocytes
Get PDFDNA damage and the enzyme poly (ADP-ribose) polymerase (PARP) associated with the pathogenesis
of numerous age-related neurodegenerative disorders. Astrocytes play crucial roles in both support metabolic
functions and cell viability of the brain. PARP regulates DNA damage and repair in the brain cells. In this study PARP
activity and DNA strand break were investigated in the astrocytes isolated from young and aged rat brain. Three and
30-month-old rats were killed by decapitation and brains were removed onto an ice cooled glass plate. Astrocytes were
isolated by sucrose density gradient centrifugation and glutamine synthetase (GS) served as a marker of the astrocytes
lineage. The specific activity of PARP was assayed in permeabilized cells by measuring the incorporation of the ADPribose moiety of [3H]NAD into the nuclear acceptor proteins. The rate of DNA strand breaks was determined using
a fluorescent dye and monitored spectrofluorimetry. An increase (about 75%) in the PARP activity was observed in
the whole homogenates of aged rats, whereas this rise was more pronounced (about 360%) when the reaction was
measured in the purified astrocyte preparations. The amount of DNA strand breaks was also higher in the astrocytes
isolated from the aged brain as compared to that of young levels. The close relationship between the level of DNA
strand breaks and PARP activity in the astrocytes suggest that these cells are susceptible to the metabolic alterations in
aging. It is concluded that the astrocytes PARP might be considered as a therapeutic target for combating age related
neurodegenerative disorders
Minocycline Prevents Depression-like Behavior After Co-administration With Dexamethasone or Cyclosporine-A in Mice
No full textBackground: In animal studies, minocycline (Mcy) has been proven to have antidepressant effects. In addition to modulating peripheral and central pro-inflammatory pathways, Mcy may regulate the hypothalamic-pituitary-adrenal (HPA) axis and the mechanistic target of rapamycin (mTOR) signaling pathway. This study aims to evaluate the antidepressant-like effect of Mcy in mice following injection of dexamethasone (Dex) or cyclosporine-A (CsA).
Methods: Male NMRI mice were randomly divided into eight groups of 6, including control, Dex 0.25 mg/kg, CsA 20 mg/kg, Mcy 40 mg/kg, Dex+Mcy, Dex+fluoxetine 20 mg/kg, CsA+Mcy, and CsA+fluoxetine. All drugs were injected intraperitoneally (except for Dex, which was subcutaneous injection) once daily for 3 days. The locomotor activity, forced swimming test (FST), and sucrose preference (SP) test were performed on day 4.
Results: Mcy alone reduced immobility time in the FST (27.0±6.4 s) compared to the control group (104±3.9 s) (P<0.001). After the co-administration of Mcy and Dex, the immobility time significantly decreased (79.5±6.5 s) compared to the Dex group (P<0.001). It also decreased following the co-administration of Mcy and CsA (67.5±20.8 s) compared to the CsA group (P<0.001). Results were similar in the groups treated with fluoxetine plus Dex or CsA. Significant differences were not observed in the locomotor activity test.
Conclusion: Mcy prevents depression-like behavior in mice during the FST when it is co-administrated with CsA or Dex. The possibility of the positive effect of Mcy on the HPA axis and the mTOR signaling pathway should be examined in further studies
Evaluating the Effect of Orlistat Administration on Depressive Behavior in Mice Following Inducing Depression by Water Avoidance Stress Model
No full textIntroduction: The weight-loss drugs can induce depression. Orlistat is one of the common weight-loss drugs, but preclinical studies about its effect on mood have not been performed. The aim of this study was evaluating the effect of orlistat alone and following inducing stress on mice depressive behavior.
Methods: In this fundamental-applied study, male white mice (27±2 g), in six groups having 7 animals were used. Orlistat was administered orally and imipramine (positive control) was injected intraperitonealy daily, depression was induced by the water avoidance stress (WAS) model during 14 days. The activity was evaluated by the Locomotor Activity Test, depression was assessed by measuring the immobility time during the forced swimming test (FST), food consumption in novelty suppressed feeding test (NSFT), and the sucrose preference test.
Results: Orlistat (25 mg/kg) did not change the locomotor activity. Stress increased the duration of immobility in the forced swimming test compared to the stress control group (98±2.2 seconds, P0.05). The difference in the results of latency and food consumption during novelty suppressed feeding test in orlistat group compared to the control group and between orlistat-WAS group compared with the WAS alone group were insignificant. In orlistat-WAS group the sucrose preference increased (69/8 %). Imipramine reduced depressive behavior in mice.
Conclusion: Orlistat administration did not induce depressive behavior in animals and it did not augment depression when administered during WAS. Evaluating the effect of chronic orlistat administration on depressive behavior is suggested
The effects of Anethum graveolens essence on scopolamine-induced memory impairment in mice
Get PDFSince Anethum graveolens (Dill) has phytoestrogenic compounds and it is proven that estrogens exert beneficial effects on cognition; the aim of this study was to understand if this plant can improve memory performance. Male Balb/c mice weighing 25-30 g were used in this study and memory was assessed by the novel object recognition task. In this method, the difference in the exploration time between a familiar object and a novel object is taken as an index of memory performance (recognition index, RI). Scopolamine significantly reduced memory index (RI = -15.5% ± 3.0). Dill essence (100 mg/kg, ip) prevented the harmful effects of scopolamine on memory (RI = 40% ± 5.5), thus RI did not differ with control animals (RI = 50% ± 5.8). In addition, 17-β estradiol also prevented memory impairment in animals (0.2 mg/kg, ip; RI = 35.8% ± 6.5). Nevertheless, the beneficial effects of dill essence were antagonized by prior injection of tamoxifen (1 mg/kg, ip; RI = -30% ± 7.8). Although phytoesrogens are not steroids, the beneficial effect of dill on memory, at least in part, may have been achieved by estrogenic receptors present in the brain. Thus dill essence could be promising in improving memory and cognition, mainly in postmenopausal women
The effect of Cinnamomum zeylanicum bark water extract on memory performance in alloxan-induced diabetic mice
Get PDFCinnamomum zeylanicum (cinnamon) has a wide range of beneficial effects including mild glucose lowering activity. The aim of the present study was to investigate whether cinnamon bark extract has the potential to improve memory performance and glucose profiles in diabetic mice. Memory was assessed by the novel object recognition task in male Balb/c mice. In this method, the difference between exploration time of a familiar object and a novel object was considered as an index of memory performance (recognition index, RI). The water extract was prepared by boiling cinnamon bark for 15 min. Alloxan induced diabetes in animals (serum glucose levels were 322 ± 7.5 mg/dL), and also impaired memory performance (RI= -3.3% ± 3.3) which differed significantly from control animals (RI = 32% ± 6.5). Although treatment with cinnamon only reduced fasting blood glucose level moderately but it improved memory performance remarkably (RI = 25.5% ± 5.6). Oxidative stress following administration of cinnamon extract was lower in diabetic mice. It was concluded that cinnamon water extract could be a useful alternative medicine in diabetic patients' daily regimen which not only reduces blood glucose levels but also improves memory performance and lipid peroxidation level
The Noradrenergic System is Partly Involved in Resveratrol Antidepressant and Anti-Obsessive Like Effects in Mice Model
Get PDFBackground and objectives: Resveratrol is a natural phenol in food particularly the skin of fruits like red grapes. It has shown biological, and antidepressant effects. The objective of the present study was to evaluate the role of adrenergic system on antidepressant and anti-obsessive effect of resveratrol. Methods: Male mice (weighing 27±2 g) were used. A tyrosine hydroxylase inhibitor, α-methyl-p-tyrosine (AMPT 100 mg/kg), α1 adrenergic receptors (AR) antagonist (prazosin, 1 mg/kg), α2-AR antagonist (yohimbine, 1 mg/kg), β-AR antagonist (propranolol, 2 mg/kg) and a tricyclic antidepressant (imipramine, 5 mg/kg), were injected before resveratrol (60 mg/kg). Locomotor activity, burring behavior during marble burring test, and immobility time during forced swimming test (FST) were evaluated. Results: No significant difference was observed in the locomotor activity between groups. The immobility time increased following pretreatment with AMPT (147.3±6.35s vs resveratrol alone 85.67±4.51s, p <0.001); marble burring behavior increased significantly, indicating the possible role of norepinephrine in resveratrol antidepressant and anti-obsessive-like effects. Propranolol (163.8±8.25 s, p <0.001) and yohimbine (151.0±6.47s, p=0.0030) pretreatment increased immobility in the FST compared to resveratrol. Pretreatment with prazosin did not cause important change in FST. Pretreatment with propranolol slightly increased marble burring behavior while no changes were observed following yohimbine or prazosin administration. Imipramine pretreatment did not have additive antidepressant effect with resveratrol and increased immobility time (136.1±16.88 s, p=0.014 vs resveratrol). Conclusion: Resveratrol antidepressant-like effect is partly mediated by the noradrenergic system, and interaction with β-AR and α2-AR. Additionally, resveratrol anti-obsessive-like property involves noradrenergic system but not the β or α-AR
Comparing the effect of clofibrate and phenobarbital on the newborns with hyperbilirubinemia
Get PDFThe aim of treating hyperbilirubinemia is preventing the serum bilirubin to reach neurotoxic levels, which is done by phototherapy or blood transfusion. However, pharmacological treatments still remain vague. Therefore the effects of adding either clofibrate or phenobarbital on
treatment outcomes was evaluated in icteric non-hemolitic newborns. Ninety neonates were
divided in three groups. Two groups were prescribed 100 mg/kg clofibrate or 5 mg/kg phenobarbital orally as single dose on arrival, in addition to phototherapy. The control group only received phototherapy. Serum bilirubin was evaluated at the reception and 12, 24, 48 and 72 hours after beginning of drug therapy. Total bilirubin levels decreased in treated groups compared with the control group in all samples taken (12, 24, 48 and 72 hours). Clofibrate effect in decreasing bilirubin level was more prominent (14 % and 32 % after 12 and 72 h respectively). In addition duration of hospitalization and length of phototherapy decreased in clofibrate and phenobarbital groups compared with control group (1.5, 2 days respectively, vs. 2.6 days). Therefore using clofibrate and phenobarbital in icteric neonates are supportive not only by decreasing the serum bilirubin level, but also by lessening the duration of hospitalization and phototherapy. Thus in addition to cost benefits for the patient these drugs can reduce the risks of transfusion, and clofibrate seems more promising in this regard
Mineralocorticoid receptors mediate cardiac remodelling in morphine-dependent rats
Get PDFAcute morphine administration decreases cardiac responses to ischaemic injury. This project has determined whether induction of morphine dependence in rats by gradually increasing morphine doses for 21 days induces structural and functional changes in the cardiovascular system because of mineralocorticoid receptor activation, as morphine increases plasma corticosterone concentrations. Morphine-dependent rats showed ventricular hypertrophy, increased collagen deposition in the left ventricle together with an increased ventricular stiffness and increased plasma malondialdehyde concentrations without changes in systolic blood pressure or thoracic aortic responsiveness. These parameters were attenuated or normalised in morphine-dependent rats treated with spironolactone (50 mg/kg/day) from days 14–21. These results suggest that morphine dependence induces ventricular remodelling and increased oxidative stress that can be prevented by the mineralocorticoid receptor antagonist, spironolactone
