ABSTRACT
Chronic stress during adolescence increases the susceptibility to many neuropsychiatric diseases in adulthood, including anxiety-like and alcohol drinking behaviors. Social isolation is a particularly profound stressor with increasing human relevance, especially during the COVID-19 pandemic, when millions of adolescents faced prolonged periods of isolation. However, preclinical rodent models of adolescent social stress have produced mixed results that are often sex, species and strain-dependent. Here we examined the effect of intermittent social isolation on alcohol intake and preference during adolescence (PND28-56) and its long-term effects and alcohol drinking on anxiety, irritability, and synaptic transmission in both male and female Wistar rats. To this goal, we developed and utilized a new model of social isolation and alcohol exposure whereby adolescent (PND28) male and female rats were intermittently socially isolated for 24h prior to 2-bottle choice (2BC) access to ethanol (20% v/v, 2h/session, Tues/Thur/Sat) vs. water, for 4 weeks. Two weeks later (young adults), all rats were tested for anxiety in the novelty induced hypophagia test and irritability-like behavior in the bottle brush test, and a subset was used to record spontaneous inhibitory GABAergic postsynaptic currents (sIPSCs) in the central nucleus of the amygdala (CeA). Additionally, we studied genetically selected Marchigian Sardinian alcohol-preferring (msP) rats to compare the effects of social isolation in a rat strain of increased alcohol preference vulnerability and high sensitivity to anxiety. Social isolation increased alcohol preference in both male and female Wistars when compared to the group-housed controls, starting from week 1 and throughout adolescence. All msP rats displayed escalation of drinking during week 1 and 2 and the effect of the isolation was observed starting from week 3 in males only. No isolation effects were observed in female msPs throughout the 4 weeks. Social isolation and alcohol drinking during adolescence increased aggressive-like behavior in male adult Wistar rats, but not females, and did not alter anxiety measures. Baseline frequency of sIPSCs was decreased in socially isolated male Wistar and msP adult rats vs. group-housed, while rise times, amplitudes, and decay times remained unchanged, indicating reduced basal presynaptic GABA release in the CeA. Together, these findings suggest that an intermittent social isolation produces increased alcohol preference in Wistar rats of both sexes and in male msPs, as well as synaptic changes in the CeA.Copyright © 2023
ABSTRACT
Objective: To find out the effects of remdesivir on the body weight of treated albino rats and its testes Study Design: Experimental Place & Duration of study: At the Anatomy Department of Baqai Medical University Karachi, from August 2021-February 2022 Material & Method: The research was undertaken to record the body weight and its testes in Albino Wistar rats treated by antiviral agent remdesivir. This drug is also recommended for the treatment of Covid-19. The albino rats were divided into 4 groups as A, B, C & D. In each group having 6 Albino Wistar rats. Group A was untreated i.e. control group while group B, C & D were treated by intraperitoneal injection with low, Intermediate and high doses of Remdesivir respectively for 10 consecutive days. A paired sample t-test was performed to determine changes in body weights before and after provision of drugs. The one-way ANOVA was conducted to compare the difference of body weight and relative weight of testes amongst all four groups. Results: The mean body weight of group A before giving any treatment was 173.10±3.42 g & after sterile saline injection intraperitoneally without the drug was 173.48±3.46 g & the difference between the two was insignificant. The mean body weight albino rats before giving any treatment to group B was 178.24±1.78 g, in group C was 174.33±2.49 g & in group D was 173.76±3.22 g. After treatment with intraperitoneal remdesivir with low, intermediate and high doses given to the rats, the mean body weight of group B, C & D was 179.88±1.87 g,177.17±2.41 g and 176.44±3.15 g respectively and the difference between the two means was highly significant (p=0.0001). The mean relative weight of tetes of rat in group A=0.713 ± 8.56 g, B=0.717 ± 15.83 g, C=0.716 ± 14.18 g and D=0.705 ± 4.15 g. There was no statistically significant difference found in the overall relative weight changes of testes amongst four groups (p=0.876). Conclusion: It has been concluded from this study that the mean body weight of animal treated with remdesivir increased significantly while weight of the testes did not affect significantly but in high dose the relative weight of testes decreases. In high dose this drug should be used cautiously as it can affect germ cells present in the testes.
ABSTRACT
Chronic stress during the developmental period of adolescence increases the susceptibility to many neuropsychiatric diseases in adulthood, including anxiety-like and alcohol drinking behaviors. Social isolation is a particularly profound stressor with increasing human relevance, especially during the COVID-19 pandemic, when millions of adolescents have faced prolonged periods of isolation. Preclinical rodent models of adolescent isolation stress have produced mixed results that are often sex, species, and strain dependent. Here, we examined the effect of intermittent social isolation on alcohol intake and preference during adolescence (PND 28-56) in male and female Wistar rats and the long-term effects of juvenile social isolation and alcohol drinking on anxiety-and irritability-like behaviors. Furthermore, we studied genetically selected Marchigian Sardinian alcohol-preferring (msP) rats to compare the effects of social isolation in a rat strain of increased innate alcohol preference and high sensitivity to stress and anxiety. We developed and utilized a new model of social isolation and alcohol exposure whereby male and female rats beginning at PND28 were intermittently socially isolated for 24h prior to 2-bottle choice (2BC) access to ethanol (20%v/v, 2h/session) vs. water. After each session, the rats were regrouped until the next day when they were isolated again. This procedure was repeated for 3 days/week across 4 weeks. Two weeks later, as young adults (PND 80), all rats were tested for anxiety in the novelty induced hypophagia test and irritability in the bottle brush test. Social isolation increased alcohol preference in both male and female Wistars when compared to the group-housed control group, starting from week 1 and throughout adolescence. All msP rats displayed escalation of drinking during week 1 and 2 and the effect of the isolation was observed starting from week 3 in males only. No isolation effects were observed in female msPs throughout the 4 weeks. Social isolation and alcohol drinking during adolescence increased aggressive-like behavior in male adult Wistar rats, but not females, and did not alter anxiety measures. Together, these findings suggest that an intermittent social isolation followed by re-grouping produces increased alcohol preference in Wistar rats of both sexes and, with a different trend, in male msPs. Ongoing studies are elucidating the underlying physiological mechanisms.
ABSTRACT
Favipiravir, a selective RNA polymerase inhibitor agent, is an antiviral drug currently used effectively in treating pandemic diseases such as Covid-19. The present study aims to determine the effects of favipiravir use on bone marrow and blood cells. Twelve male Wistar rats were divided into two groups, namely control and favipiravir groups. Physiological saline at a dose of 1 ml/kg was administered to the rats in the control group by oral gavage for 10 days. Rats in the favipiravir group were administered favipiravir by oral gavage at a dose of 200 mg/kg for 10 days. At the end of the study, the blood tissue was collected from the heart, and bone marrow samples were collected from the femur bone of the rats sacrificed under anesthesia. The hematologic parameters in the blood samples obtained were measured using an auto-analyzer device with the help of rat compatible kits. Bone marrow cell counts were performed by examining structural changes and myeloid and erythroid cell series in the smear samples. The results obtained in the study revealed that favipiravir use caused a decrease in the counts of some hematologic parameters containing erythrocytes, lymphocytes, and monocytes. In addition, it was determined that the ratio of myeloid and erythroid cells in bone marrow smears changed significantly with the use of favipiravir. It was concluded that treatment with favipiravir caused suppression of erythrocyte and some leukocyte series. The suppressor effects were also determined in bone marrow cell series in the rats.
ABSTRACT
Objective: To see the effects of Raj Nirwan Bati (RNB) on the hematobiochemical parameters, coagulation tests, and histopathological changes in the lungs, liver, kidneys and spleen and also to evaluate the immunomodulatory activity of RNBin Wistar rats. Methods: A total of 24 adult albino Wistar rats (of bodyweight 200-250 g) of either sex were divided into 3 groups. In the normal control group (n=8), no drug was administered and in the rest of the groups (A and B), RNB@ 26 mg/kg body weight./day and 260 mg/kg body weight/day respectively were administered orally for a period of 14 d. The blood samples were collected from the jugular vein at zero d (before drug administration) and after the 14th d of drug administration in both groups (A and B). The organ samples (lungs, liver, kidneys, and spleen) were collected after euthanizing the rats using Ketamine anesthesia overdose intraperitoneally (IP) after the 14th d of drug administration. White Blood Cells (WBC), Red Blood Cells (RBC), Hemoglobin (Hb), Hematocrit (HCT), Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin(MCH), Mean Corpuscular Hemoglobin Concentration(MCHC), number of platelets, Differential Leucocyte Count(DLC) i.e. the percentage of neutrophils, lymphocytes, eosinophils, monocytes and basophils, neutrophil adhesion percentage, Prothrombin test (PT), Activated Partial Thromboplastin Time (APTT), fibrinogen, D-dimer, Lactate Dehydrogenase (LDH), urea, creatinine, Aspartate Amino Transferase (AST), Alanine amino Transferase (ALT), Alkaline Phosphatase (ALP), C-Reactive Protein (CRP) were evaluated and histological examination of organs were done. Results: After statistical analysis, it was found that the decrease in TLC, RBC, Hb, HCT, and LDH in Wistar rats after RNB intervention in Group A as compared to that of before RNB intervention, was found to be statistically significant (P=0.001, P=0.002, P=0.001, P=0.039, and P=0.008). On the other hand, an increase was observed in MCV, Urea, Creatinine and ALT values in the Wistar rats after RNB intervention in Group ‘A’ as compared to that of before RNB intervention and this increase in values was statistically significant (P=0.007, P=0.001, P<0.001 and P=0.038). After RNB intervention in Group B, the increase in MCH, fibrinogen concentration, and monocytes percentage, was found to be statistically significant (P=0.004, P=0.033, and P=0.001) as well as the decrease in PT and APTT was statistically significant (P=0.007and P=0.002). After comparing the Mean Hematobiochemical and coagulation test parameters in the rats of Group A and Group B, after RNB intervention, it was observed that the concentration of Urea, Creatinine, APTT, and D-dimer were less in Group B as compared to that of Group A and this difference was statistically significant(P<0.001, P<0.001, P<0.001 and P=0.022). Histologically the findings in the lungs of group B were more distortion of lung architecture, most of the alveoli become collapse and make emphysematous changes, more diffuse inflammatory infiltrate within interalveolar septa and around bronchioles as compared to Group A. In the liver of group B rats, the histological findings were mild to moderate distortion of lobular architecture, healthy hepatocytes with more activation of kupffer cells as well as larger and more aggregates of inflammatory cells as compared to group A. Histological findings of kidneys in group A and group B rats were similar to that of control group rats. Conclusion: The results suggest that the RNB is having an immunomodulatory effect. It might be helpful in the restoration of coagulation factors and can help treat the COVID patients. No harmful effects on the lungs, liver, kidney, and spleen were seen. These findings may act as baseline data for planning further clinical trials in human study subjects to evaluate the effects on various comorbidities.
ABSTRACT
Introduction. Social isolation has become an important public health issue since the COVID-19 pandemic outbreak. Lack of social contacts is especially challenging for adolescents because social interaction at this age is essential for healthy neuroendocrine system maturation. Aim. This study aimed to investigate the effect of adolescent social isolation on synaptic plasticity in the dorsal and ventral hippocampus of rats. Methods. Male Wistar rats were randomly assigned into either isolation-housing or group-housing immediately after weaning at postnatal day 23-25. After 4 weeks of different housing conditions, acute hippocampal slices (400 ±m thick) were prepared from dorsal (DH) and ventral (VH) poles of the hippocampus. Field excitatory postsynaptic potentials (fEPSP) were recorded from the stratum radiatum of the hippocampal CA1 region after stimulation of the Schaffer collateral. Long-term potentiation (LTP) was elicited by a high-frequency tetanic stimulation (HFS) train (100 Hz, 1 s), after which changes in the fEPSP were recorded. The period between 1 and 10 minutes after HFS was defined as short-term potentiation (STP). LTP was evaluated by averaging synaptic responses from 30 to 40 minutes after HFS. Results. We found that socially isolated rats had increased STP in the VH (166.4 ± 7.3 % vs. 137.1 ± 5.0 % in group-housed rats, p<0.05), while no changes were observed in the DH (165.3 ± 4.9 % vs. 162.3 ± 4.1 % in group-housed rats). Moreover, group-housed rats showed significant dorsoventral differences in STP (p<0.05), while fEPSP slopes in the DH and VH of isolated rats were similar. We also found that this dorsoventral heterogeneity was maintained in LTP of the group-housed rats (group-housed DH: 142.2 ± 8.3 % vs. group-housed VH: 110.9 ± 4.6 %, P<0.05), while there was no difference between DH and VH in the isolated group (isolated DH: 134.6 ± 8.9 % vs. isolated VH: 122.0 ± 5.6 %). Conclusions. Our results indicate that prolonged adolescent social isolation enhances short-term potentiation in the ventral hippocampus and abolishes dorsoventral heterogeneity in short-term and long-term potentiation. These alterations in hippocampal synaptic plasticity may have a role in the cognitive and behavioral disorders induced by social isolation.