Analysis of depression-like behavioral performances of mouse models of vitiligo / 中华皮肤科杂志

Objective:To observe and analyze depression-like behavioral performances of mouse models of vitiligo.Methods:Fifteen female C57BL/6 mice aged about 9 weeks were modeled for vitiligo. Whether the mouse models of vitiligo were successfully constructed or not was determined by macroscopy and full-thickness epidermal immunofluorescence staining of mouse tail tissues on day 23 after the start of the experiment; on day 8 (pre-modeling stage) and day 21 (early modeling stage), the elevated plus maze test and the open field test were used to evaluate the behavioral performances of the mice, including the number of entry into the open arms, percentages of time spent in the open arms, percentages of time spent in the central area and total distance traveled, aiming to assess whether depression-like behaviors were exhibited in the mouse models of vitiligo. To further clarify the degree of the impact of vitiligo modeling on the depression-like state in mice, 20 female C57BL/6 mice were equally divided into 2 groups: vitiligo modeling group and vitiligo modeling + chronic restraint stress group; the mice in the vitiligo modeling + chronic restraint stress group were subjected to chronic restraint stress on day 9, that is, these mice were placed in centrifuge tubes and restrained for about 6 hours every day for 28 consecutive days; on days 7, 22, 29 and 38 after the start of vitiligo modeling, the above-mentioned behavioral indicators were determined by the elevated plus maze test and open field test in the 2 groups. Repeated measurement data in a single group were compared before and after treatment by using paired t-test, and repeated measurement data at multiple time points were compared by using two-way repeated measures analysis of variance. Results:By macroscopy, the mice gradually developed well-defined white patches on the tail skin during vitiligo modeling, which were similar to the clinical manifestations of vitiligo patients; on day 23, full-thickness epidermal immunofluorescence staining of the mouse tail tissues was conducted and showed obvious infiltration of CD8 + T cells and a decrease in the number of Melan-A-positive epidermal melanocytes under a laser confocal microscope, which were consistent with typical pathological characteristics of vitiligo; based on the macroscopic results and immunofluorescence findings, a total of 12 mouse models of vitiligo were successfully constructed on day 23. The elevated plus maze test showed that the number of entry into the open arms and the percentages of time spent in the open arms were significantly lower in the 12 mouse models of vitiligo on day 21 (2.33 ± 1.78 times, 5.01% ± 5.27%, respectively) than in those on day 8 (10.75 ± 2.30 times, 29.20% ± 12.48%, t = 9.63, 6.36, respectively, both P < 0.001) ; the open field test showed that the percentages of time spent in the central area and total distance traveled were also significantly lower in the mouse models on day 21 (2.31% ± 1.53%, 2 518.31 ± 528.38 cm, respectively) than in those on day 8 (4.47% ± 2.65%, 3 533.45 ± 465.47 cm, t = 2.40, 5.47, P = 0.036, < 0.001, respectively). In the chronic restraint stress test, a total of 14 mouse models of vitiligo were successfully constructed on day 23, including 5 in the vitiligo modeling group and 9 in the vitiligo modeling + chronic restraint stress group. There were no significant differences in the number of entry into the open arms, percentages of time spent in the open arms, percentages of time spent in the central area, and total distance traveled between the vitiligo modeling group and the vitiligo modeling + chronic restraint stress group on days 7, 22, 29, and 38 ( F = 0.21, 0.20, 0.46, 2.35, P = 0.889, 0.893, 0.719, 0.134, respectively) ; moreover, all the above indicators significantly changed over time (all P < 0.001), except for the total distance traveled ( P = 0.422) . Conclusion:The mouse models of vitiligo developed depression-like behavior at the early modeling stage, and the degree of depression could not be further deepened by chronic restraint stress on the basis of vitiligo modeling.

Changes in expression of estrogen receptor α and β associated with anxiety-like behavior of dams in dams-offspring separation of C57BL/6 J mice / 解剖学报

Objective To investigate the effects of dams-offspring separation on anxiety-like behaviors of dams, and if these anxiety-like behaviors of dams are associated with estrogen receptorα(ERα) and β( ERβ)in some brain regions. Methods Thirty C57BL/6 J female mice were divided into three groups, control group (CG, n= 10,non-isolated group), short-term separation group( SG,/i= 10, dams were separated from their offspring for 15 minuts per day from the second day to the tenth day after childbirth ) and long-term separation group ( LG, n = 10, dams were separated from their offspring for 3 hours per day from the second day to the tenth day after childbirth ). Anxiety-like behaviors of dams were evaluated in an open-field (OF) and elevated plus-maze test ( EPM ). The level of ERα- immunoreactive neurons (ERα-IRs) and ERβ-immunoreactive neurons (ERβ-IRs) in three brain regions including medial preoptic area (mPOA), hypothalamic ventromedial nucleus (VMH) and medial amygdaloid nucleus ( MeA) were analyzed. Results In OF, compared to CG group and SG group, LG group had significantly less time in center area, crossing number and total distance(P0.05 ). In EPM, compared to CG group and SG group, LG group had significantly less percentage of time, distance in open arms and total distance(P<0.001 ). Compared to CG group and SG group, LG group had significantly less ERa-IRs and ERβ-IRs in mPOA, VMH, and MeA(P<0.01). Conclusion Dams that are long-termly separated from their offspring may have anxiety-like behavior, and this behavior may be related to the significant reduction of ERa and ERβ in these brain regions.

Phytochemical And Pharmacological Study Of Ashwagandha (withania Somnifera) Wild And Cultivated Varieties

Ashawagandha is herb used for various kinds of disease especially as a nervine tonic. Considering these facts many scientific studies were carried out and its memory, anti-stress activities were studied in detail. Aims and Objectives: To study the Phytochemical analysis and Pharmacological Study of Ashwagandha (Withania somnifera) varieties and Withania somnifera (L.) Dunal wild purified with milk steam (WSWM) root powder. To study the efficacy of Wild and Cultivated varieties of Ashwagandha on rats through Elevated Plus Maze test and Morris Water Maze (MWM) model. Materials and Methods: The formulations Withania somnifera (L.) Dunal wild (WSW) root powder, Withania somnifera (L.) Dunal Nagori (WSN) root powder, Withania somnifera (L.) Dunal wild purified with milk steam (WSWM) root powder, PG (Wheat powder placebo) were subjected to preliminary phytochemical screening for the detection of various chemical constituents present. Animal experimentation was done on Wistar Albino Rats obtained from the animal house attached and are divided into three groups consisting of 6 rats per group. Nootropic agents are effectively screened using this paradigm in scopolamine-induced dementia. Elevated Plus Maze and Morris Water Maze (MWM) model are based on this phenomenon. Results: By performing phytochemical analysis, Withania somnifera (L.) Dunal Nagori (WSN) showed the presence of alkaloids, carbohydrates, glycosides, phytosterols, saponins, proteins and amino acids. Withania somnifera (L.) Dunal wild purified with milk steam (WSWM) showed the presence of alkaloids, carbohydrates, glycosides, proteins and amino acids and wheat powder placebo (PG) showed the presence of alkaloids, carbohydrates, glycosides, saponins, phenolic compounds, tannins, proteins amino acids and flavonoids. Conclusion: The formulation group 3 (WSWM) showed remarkable reduction in the transfer latency time (in elevated plus maze test) from the acquisition day to the retention day and therefore considered Group 3 is statistically significant. The formulation group 3 (WSWM) showed remarkable reduction in the latency scores in Morris water maze and hence Group 3 (Ashwagandha wild purified with milk steam (WSWM) root powder) is statistically significant.

Cafeteria diet in breastfeeding dams promotes anxiolytic effects, accumulation of adipose tissue, and impacts offspring development / La dieta de la cafetería en las madres que amamantan promueve los efectos ansiolíticos y la acumulación de tejido adiposo, y afecta el desarrollo de la descendencia

The aim of this study was to evaluate the nutritional and behavioral effects of a cafeteria diet in dams during the breastfeeding period and in their offspring from weaning until early adulthood (70 days old). Pregnant Wistar rats were fed a chow diet until delivery. Postnatally (D0), litters were culled to 8 pups and lactating dams received control (CTRL n= 6) or cafeteria (CAF n= 6) diets and water ad libitum. At the end of the breastfeeding period, male offspring were placed in individual boxes receiving the same treatment from their respective dams (CTRL or CAF) until adulthood (70 days). All nutritional and behavioral evaluations were performed with the dams (n= 12) during the breastfeeding phase and with the male offspring (n= 24) after weaning to adulthood. CAF dams demonstrated a lower caloric and protein intake; higher intake of fats; loss of weight; greater accumulation of adipose tissue; and an anxiolytic effect. CAF male offspring showed lower caloric intake; higher intake of fats; and accumulation of adipose tissue. In addition, these animals continued to have decreased body weight, body length and tibia-femur length in relation to CTRL. In dams, a cafeteria diet promoted alterations in body composition and anxiety, and in offspring the diet resulted in adequate development.

El objetivo de este estudio fue evaluar los efectos nutricionales y de comportamiento de la dieta de la cafetería en las madres durante el período de lactancia materna y en su descendencia desde el destete hasta la edad adulta temprana (70 días de edad). Ratas Wistar embarazadas fueron alimentadas con una dieta estándar hasta el parto. Postnatalmente (D0), las camadas se ajustaron en 8 crías y las madres lactantes recibieron las dietas control (CTRL n= 6) o cafetería (CAF n= 6) además de agua ad libitum. Al final del período de lactancia materna, las proles machos fueron colocados en cajas individuales recibiendo el mismo tratamiento de sus respectivas madres (CTRL o CAF) hasta la edad adulta (70 días). Todas las evaluaciones nutricionales y comportamentales se realizaron con las madres (n= 12) durante la fase de lactancia y con la prole masculina (n= 24) después del destete hasta la edad adulta. Las madres CAF demostraron una menor ingesta calórica y proteica; mayor ingestión de grasas; pérdida de peso; mayor acumulación de tejido adiposo; y un efecto ansiolítico. La prole masculina CAF presentó menor consumo calórico; mayor ingestión de grasas; y la acumulación de tejido adiposo. Además, estos animales presentaron menor peso corporal, longitud corporal, y longitud de la tibia-fémur, en relación a CTRL. En las madres, la dieta de cafetería promovió cambios en la composición corporal y ansiedad, y en la prole la dieta comprometió el desarrollo adecuado.

In-Vivo Study on Anxiolytic Effects of Hydroalcoholic Extract of Agaricus blazei Murill

Background: Anxiety involved panic attacks either having or not having social fear, social anxiety disorder, generalized anxiety disorder as well as separation anxiety disorder is known to be marked mental diseases. It is related to high medical cost and a significant load of disease. Agaricus blazei Murill (AbM) is a mushroom and possesses immunemodulating and antimicrobial effects both in-vivo and in-vitro and as well as it has been used to treat cancer, hepatitis, dermatitis, and hyperlipidemia traditionally. Method: In this experiment evaluation of anxiolytic effect of AbM on mice has been done by using Elevated Plus Maze test, open field test and motor co-ordination test by rotarod. Mice (Mus musculus) weighing 22-25 grams, were divided into 4 groups (n=6). Oral administration of hydro-alcoholic extract of AbM was utilized in 2 doses i.e. 136.5 mg/kg and 273 mg/kg. Group, I received vehicle (distilled water 10 ml/kg), p.o. Group II received standard (diazepam 1 mg/kg), i.p. Group III and IV orally received hydro-alcoholic extract of AbM (136.5 mg/kg and 273 mg/kg, respectively). Result: In Elevated Plus Maze test, oral administration of hydro-alcoholic extract of AbM (136.5 mg/kg and 273 mg/kg, respectively) exhibited significant (p<0.01) elevation in the percentage of number of open arm entries (48.0 ± 1.1% and 48.93 ± 2.1% respectively) and time spent in open arm (14.92 ± 1.9% and 84.17 ± 2.4%). Conclusion: Hence it is concluded that hydro-alcoholic extract of AbM can be a new therapeutic agent to treat anxiety.

Anxiolytic Action of Taurine via Intranasal Administration in Mice

Taurine has a number of beneficial pharmacological actions in the brain such as anxiolytic and neuroprotective actions. We explored to test whether taurine could be transported to the central nervous system through the intranasal route. Following intranasal administration of taurine in mice, elevated plus maze test, activity cage test and rota rod test were carried out to verify taurine’s effect on anxiety. For the characterization of potential mechanism of taurine’s anti-anxiety action, mouse convulsion tests with strychnine, picrotoxin, yohimbine, and isoniazid were employed. A significant increase in the time spent in the open arms was observed when taurine was administered through the nasal route in the elevated plus maze test. In addition, vertical and horizontal activities of mice treated with taurine via intranasal route were considerably diminished. These results support the hypothesis that taurine can be transported to the brain through intranasal route, thereby inducing anti-anxiety activity. Taurine’s anti-anxiety action may be mediated by the strychnine-sensitive glycine receptor as evidenced by the inhibition of strychnine-induced convulsion.

Influence of Naogongtai Formula on Hippocampus Monoamine Neurotransmitters and Their Metabolites inRats in Elevated Plus-maze Test / 中国药师

Objective:To observe the influence of Naogongtai formula on hippocampus monoamine neurotransmitters and their metabolites in rats in elevated plus-maze test, and explore the mechanism of antihypertensive effect of brain tegument peptide. Methods:The effects of two doses of Naogongtai formula on the anxiety behavior of rats were observed by using the rat model of elevated malaria anxiety (EPM). The contents of monoamine neurotransmitters and their metabolites in hippocampus of rats were determined by HPLC-FLD. Results:Compared with those in the blank control group,the percents of open arms time and entries in the high dosage of Naogongtai formula group significantly increased (P < 0.05),and the percent of open arms entries in the low dosage of Naogongtai formula group significantly increased (P < 0.05). Compared with that in the blank control group, the content of 5-HT in the high dosage of Naogongtai formula group significantly decreased (P < 0.05) and the content of HVA significantly increased (P < 0.05). Conclusion:In the EPM test, Naogongtai formula shows a certain anti-anxiety effect, and the determination of monoamine neurotransmitters in hippocampus of rats may be related to the reduction of rat hippocampal 5-HT content.

Critical neuropsychobiological analysis of panic attack- and anticipatory anxiety-like behaviors in rodents confronted with snakes in polygonal arenas and complex labyrinths: a comparison to the elevated plus- and T-maze behavioral tests

Objective: To compare prey and snake paradigms performed in complex environments to the elevated plus-maze (EPM) and T-maze (ETM) tests for the study of panic attack- and anticipatory anxiety-like behaviors in rodents. Methods: PubMed was reviewed in search of articles focusing on the plus maze test, EPM, and ETM, as well as on defensive behaviors displayed by threatened rodents. In addition, the authors’ research with polygonal arenas and complex labyrinth (designed by the first author for confrontation between snakes and small rodents) was examined. Results: The EPM and ETM tests evoke anxiety/fear-related defensive responses that are pharmacologically validated, whereas the confrontation between rodents and snakes in polygonal arenas with or without shelters or in the complex labyrinth offers ethological conditions for studying more complex defensive behaviors and the effects of anxiolytic and panicolytic drugs. Prey vs. predator paradigms also allow discrimination between non-oriented and oriented escape behavior. Conclusions: Both EPM and ETM simple labyrinths are excellent apparatuses for the study of anxiety- and instinctive fear-related responses, respectively. The confrontation between rodents and snakes in polygonal arenas, however, offers a more ethological environment for addressing both unconditioned and conditioned fear-induced behaviors and the effects of anxiolytic and panicolytic drugs.

Effect of maternal separation stress on behavior of neonatal rd mice / 中国比较医学杂志

Objective To evaluate the effect of maternal separation stress on the behavior of neonatal rd mice.Methods Neonatal rd mice were divided into maternal separation (MS) group (n=9) and control group (n=9).MS-stress was induced in the MS group by 4-hour-separation per day for 28 days.Open field test,elevated plus maze test,forced swim test and tail suspension test were used to evaluate the anxiety-like and depression-like behavior of the neonatal rd mice.Results The stay time and distance travelled of MS group in the central zone were 0.88％ and 28.17±5.65 cm,respectively,significantly shorter than that of the control group (2.61％,109.9±9.79 cm.P =0.04,P =0.001).Compared with the control group,the stay time in open arms of the MS group was significantly decreased (P<0.01),while the immobility time in forced swim test and tail suspension test of the MS group were 126.5±10.22 s and 21.56±6.83 s,significantly longer than that of the control group (77.75±16.83 s,P =0.02,7.37±3.22 s,P =0.03).Conclutions The 28-day maternal separation stress can significantly increase the anxiety-like and depression-like behavior in neonatal rd mice.

Elaeocarpus ganitrus: its beneficial antiparkinsonian effect in MPTP induced motor and non-motor impairments in mice.

Aim: Elaeocarpus ganitrus (Family: Elaeocarpaceae), has shown beneficial role in the treatment of depression, convulsions and asthma. This study was undertaken to evaluate the antiparkinson effect of E.ganitrus. Materials and methods: Swiss albino mice of either sex were divided into 06 groups (n =12). 1st group mice were given 0.5% carboxy methyl cellulose (orally), 2nd group were administered MPTP (2 doses, each dose 20 mg/kg at 2 hr. interval, i.p.). Whereas 3rd, 4th and 5th groups - were administered with E. ganitrus (100, 200, and 400 mg/kg/day, orally), respectively, along with MPTP. Group 6- received Levodopa (30mg/kg, i.p,) along with MPTP. To evaluate anti-Parkinson effect, hanging wire test, tardive dyskinesia test and elevated plus maze test were performed on the1st day and on 8 th day. One way ANOVA followed by post-hoc Tukey test, with p<0.05 was considered statistical significant. Results: E.ganitrus (200 and 400 mg/kg, p.o.) was found to increase the hanging time significantly (p <0.001) in hanging wire test and significantly decreased (p <0.001) the Vacuous Chewing Movements (VCMs) in tardive dyskinesia test as compared to MPTP group. E.ganitrus (200 and 400 mg/kg, p.o.) was found to significantly increase (p <0.001) the no. of entries and time spent in open arm and significantly decreased the no. of entries and time spent in closed arm (p <0.001) compared to MPTP treated group. Conclusion: The results of the present study conclusively showed that E.ganitrus has beneficial effect in MPTP induced experimental model of Parkinson’s disease.

To investigate the role of Memantine as anxiolytic in elevated plus maze test and as antidepressant in tail suspension test in Swiss albino mice.

Background: The magnitude of improvement seen with present conventional medicines for anxiety and depression remain disappointing thereby providing a scope for the study of newer drugs. In the literature, there is evidence demonstrating the modulation of N-methyl-D-aspartate (NMDA)receptors in anxiety and depression. The present study is undertaken to evaluate the antianxiety effect of memantine in elevated plus maze (EPZ) test and its antidepressant effect in tail suspension test (TST)in Swiss albino mice. Methods: Animals were divided into six groups (n=6). First group mice were given normal saline (10 ml/kg), second group were administered lorazepam (0.5 mg/kg), third group with memantine (3 mg/kg) and fourth group with memantine plus lorazepam, fi fth group was administered amitriptyline (10 mg/kg)and sixth group received memantine plus amitriptyline. All drugs were administered by intraperitoneal route daily for 7 consecutive days. Results were analyzed by one-way ANOVA followed by post-hoc Tukey’s test. Results: Memantine treated mice showed signifi cant increase (p<0.001)in time spent and number of entries in open arm and signifi cant decrease in time spent and number of entries in closed arm in EPZ when compared to control group. Duration of immobility was signifi cantly (p<0.001)reduced in animals treated with memantine when compared to the control group in TST. Conclusions: NMDA antagonist, memantine has showed signifi cant antianxiety effect in EPZ test and antidepressant effect in TST.

Profile of pharmacological effects of combination of buspirone with selected antidepressants: a behavioral study in mice.

Background: Antidepressants are commonly prescribed drugs. Co-existing disorders like anxiety require therapy with other drugs. The profiles of pharmacological effects of these drugs on central nervous system are influenced by the administration of these drugs either as single or combination. This study is designed to observe the behavioral effects of antidepressants along with the antianxiety agent buspirone in mice. Methods: Four antidepressant drugs belonging to different groups are selected for the study. Amitriptyline, citalopram, venlafaxine and mirtazapine are given orally for 2 weeks. Subsequently, buspirone is added to each antidepressant drug for a period of 3 weeks. The behavioral effects in mice are observed at weekly intervals using photoactometer, rotarod, forced swim test and elevated plus maze. Results: The antidepressant drugs amitriptyline and citalopram showed any change in spontaneous motor activity recorded by photoactometer. In rotarod test venlafaxine showed an increase in values, which showed further increase when buspirone was added. In the forced swim test also, venlafaxine showed a different pattern of effects when compared to other antidepressants. In the elevated plus maze test, the four antidepressants did not show any increase in the time spent in open arm excepting citalopram. Venlafaxine showed an increase in time spent in closed arm. Conclusions: The test drugs do not show any significant depression of central nervous system at the dose used. Venlafaxine showed a different pattern of activity in the rotarod test and swim test. The variation in response is attributed to their effects on central neurotransmitter.

Morphine Treatment in Neonate Rats Increases Exploratory Activities: Reversal by Antagonist D2 Receptor.

Aims: Morphine treatment in early life is a practice widely used in paediatric intensive care units. However, the consequences of this treatment on behavioural responses throughout life have been poorly studied. It is well known that behavioural symptoms after morphine exposure are presumed to depend on certain changes in the dopaminergic system, and there is a strong evidence of the involvement of D2 receptor. In this way, our objective was to evaluate whether 5 μg morphine administration, once daily for 7 days in 8-day-old rats (P8), alters exploratory and anxiolitic-like behaviours over short- (P16) and medium-term (P30) periods in the open-field (OF) and elevated-plus maze (EPM) tests, and to verify the involvement of the D2 receptor in the behaviour changes. Place of Study: All experiments were performed at Animal Experimentation Unit of Hospital de Clínicas de Porto Alegre. The experimental protocol was approved by the Institutional Committee for Animal Care and Use (GPPG-HCPA protocol No: 08345). Methodology: Wistar rats with 8-day-old (P8) received 5 μg of morphine administration, once daily for 7 days. The exploratory and anxiolitic-like behavious were analyzed in P16 and P30 by OF and EPM tests. At the ages where we observed significant differences in behaviour responses in both tests, the control and morphine groups were subdivided into three groups, each one designed to evaluate the effect of 0.2 mg/kg, 0.5 mg/kg or vehicle of i.p. administration of a dopamine D2 antagonist receptor (Haloperidol). Results: At short-term (P16) morphine group showed an increase in grooming, as well increase in exploratory behaviours at P30 in the OF test. In addition, anxiolytic-like behaviours were observed in the morphine group, such as increase of percentage of open arms behaviours and non-protected head dipping at medium-term in the EPM test. At the ages at which differences in behaviours were observed, both groups (control and morphine) received D2 antagonist receptor (haloperidol) 30 min before each test. All behaviours changes seen in the morphine group at P30 were totally reversed by haloperidol administration. Conclusion: Our findings demonstrate that morphine treatment in neonate period promotes behavioural changes in OF and EPM at P16 and P30. However, only alterations observed at P30 depend, at least in part, of dopaminergic system, particularly of the D2 receptor.