Depressive-Like Behavior Induced by Long-Term Ouabain Administration Accompanied Alteration in Neuroinflammation Parameters in Rats

Objective: The present study aims to investigate the effects of Lithium (Li) on manic- and depressive-like behaviors and inflammatory parameters in rats submitted to the bipolar disorder (BD) model induced by ouabain (OUA). Material and methods: Adult male rats received a single intracerebroventricular (ICV) injection of OUA or artificial cerebrospinal fluid (aCSF). On the fourth day after the ICV injection, the rats received intraperitoneal injections of saline (NaCl 0.9%) or Li (47.5 mg/kg), two times a day, for 14 days. On the seventh day after OUA injection, the locomotor activity was assessed (open field test), and on the fourteenth day, locomotion was evaluated again, which was followed by the forced swimming test to evaluate depressive-like behavior. After euthanasia, inflammatory parameters were evaluated in the frontal cortex and hippocampus. Results: After seven days of OUA administration, the animals showed a hyperactive behavior that was reversed by treatment with Li. After 14 days of ICV injections, rats exhibited a depressive behavior. Regarding the inflammatory parameters, measured after 14 days of the ICV infusions, OAU induced an increase in the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor α, and cytokine-induced neutrophil chemoattractant-1. In contrast, Li treatment decreased these parameters. Conclusion: The animal model of BD induced by an OUA is able to induce neuroinflammation, which supports its construct validity for the BD research.

Elucidating the Effects of a Cryptomeria fortunei Forest Environment on Overall Health Based on Open Field Testing of Mice

In order to elucidate the impact of fortunei forest environment on overall health, the effect of the Cryptomeria fortunei forest environment on mice was examined. Using an OFT (Open Field Test), the behavior of mice in fortunei forest and in an indoor environment (used as a control) was analyzed, while minor changes in climate, oxygen, and suspended particulate matter were observed and recorded simultaneously. The results indicated that the two environments were significantly different in regard to relative humidity, wind speed, and the oxygen content of air, while there were no significant differences in temperature. Importantly, spontaneous activity behavioral indicators in mice were significantly different. Mice in the Cryptomeria fortunei environment (LS group) spent less time in the corners and near walls in comparison to mice in the indoor environment (CK group). Compared with indoor control mice, for the mice exposed to forest environments total distance traveled, central grid distance, frequency of movement through the central grid, frequency of standing, and body mass significantly increased; The number of fecal grains significantly decreased. The spontaneous activity behavioral indicators changed over time stages. In the early stages there were no differences, but after accumulation of environmental effects in the late stages, significant differences were evident. The above results showed that the Cryptomeria fortunei forest environment increased excitability and cognitive ability of mice, was able to effectively alleviate anxiety, and was able to emotionally relax and improve the appetite of the mice.

Assessment of homeopathic medicine Aconitum napellus in the treatment of anxiety in an animal model

Background: Aconitum napellus is a classic resource of complementary medicine for the treatment of patients exhibiting neurological symptoms of anxiety. Aim: To assess the action of homeopathic medicine Acon in the treatment of generalized anxiety in an experimental model using rats. Methods: 48 adult (two to three months old) male Wistar rats (Rattus rattus) were randomly divided in six groups (n= 8/treatment) and given the following treatments by gastric tube along 10 days: 1) control (diazepam 1 mg/kg/day); 2) negative control (0.15 mL saline solution/day); 3) ACH6 (0.15 mL Acon (6cH/day); 4) ACH12 (0.15 mL Acon 12cH/day); 5) ACH30 (0.15 mL Acon 30cH/day); and 6) ALC30 (0.15 mL 30% cereal alcohol/day). Behavioral effects were blindly and randomly assessed in elevated plus maze (EPM) and open field test. Results: Acon in dilutions 12cH and 30cH exhibited possible anxiolytic effects on the central nervous system (CNS) since they increased the number of entries in the EPM open arms (12cH and 30cH) and the permanence time in the EPM open arms (30cH only). In the open field test the homeopathic preparations did not show effects on the locomotor system of rats. Conclusion: Dilutions 12cH and 30cH of Acon exhibited anxiolytic effects on the CNS in an animal experimental model.

Garcinia camobogia extract alters anxiety, sociability, and dopamine turnover in male Swiss albino mice

Obesity is a global concern, closely allied with somatic and psychosomatic disorders. Herbal drugs are available in modern medicine to treat obesity. Garcinia camobogia being used by so many people trying to lose weight produces various systemic side effects. The study was conducted to assess its effect on anxiety, sociability, and dopamine turnover in male mice. Twenty-one male Swiss albino mice of either were divided into three groups with seven mice in each group. Control group was given distilled water (0.5 ml p.o.) and the other two groups received Garcinia cambogia extract at two different doses, a low and a higher dose (100 mg/kg and 500 mg/kg. p.o.) Each animal received a single oral dose daily, which was administered using an oral gavage for fourteen consecutive days. Effect of test drugs on anxiety was evaluated using open field test. Sociability and social novelty were evaluated using three chambers test. Results (mean ± SD) were analyzed using one-way ANOVA test followed by Tukey’s test. Garcinia cambogia extract significantly increased the time spent in the corners in the open field test, significantly reduced sociability and social novelty in the three-chamber test, significantly reduced dopamine turnover in the brain with a significant decrease in dopamine metabolite homovanillic acid (HVA) and increased D2 receptor expression in ventral tegmental area. Garcinia cambogia extract have significant anxiogenic effect along with reduced sociability and social novelty in male mice. Moreover, these effects could be related to the altered dopamine turnover and D2 receptor expression in mice brain. Article Highlights Chronic used of alcoholic extract of Garcinia campbogia lead to a significant increase in anxiety that was manifested by the reduced time in the center zone and increased immobility in the open field test. Garcinia camobogia chronic administration has a profound impact on sociability and social novelty with a significant decrease in both behavioral patterns compared to the control group. These effects could be attributed to the noticed change in the dopamine turnover in the brain with a significant decrease in dopamine metabolite (HVA) and an upward expression of D2 receptors in return.

Effects of Terazosin, Silodosin and Alfuzosin on Depression and Anxiety in Mice

Aims: Benign prostatic hyperplasia (BPH) is common urological disease, is characterized by lower urinary tract syndrome, usually associated with sexual dysfunctions. The aim of present study is to investigate the effects of terazosin, silodosin and alfuzosin which are the main treatment options for BPH on depression and anxiety to understand whether these drugs may be effective in BPH caused mood disorders. Study Design: All the drugs were given intraperitoneally (i.p.) in a volume of 0.1 ml per 10 g body weight of mice. Drugs were given 30 min before the experiment. We investigated the effects of terazosin, silodosin and alfuzosin on depression and anxiety, in mice. Place and Duration of Study: Sample: Department of Pharmacology and Department of Urology, Sakarya University, Animal Research Center, between June 2019 and September 2020. Methodology: Here, we examined the effects of terazosin (0.5, 1, 2 mg/kg), silodosin silodosin (1, 3, 10 mg/kg) and alfuzosin (3, 6 and 9 mg/kg) on depression and anxiety by using forced swimming test and elevated plus maze test, respectively, in mice (n:96). Additionally, the locomotor activity was evaluated by open field test. Results: All doses of terazosin, alfuzosin and silodosin significantly increased immobility time, compared to saline group. Silodosin and alfuzosin prolonged the time spent in open arms but terazosin decreased the time spent in open arms compared to saline group. Terazosin, silodosin (1 and 3 mg/kg) and alfuzosin (3 and 6 mg/kg) did not have any effect on the number of entries into the open arms while silodosin (10 mg/kg) and alfuzosin (9 mg/kg) increased the number of entries into open arms. Conclusion: We found that silodosin and alfuzosin had antidepressant and anxiolytic-like effects, while terazosin had depressant and anxiogenic effects. Patients with BPH who need antidepressant and anxiolytic treatment can be treated with a single drug instead of multiple medications.

Lipocalin-2 Regulates Hippocampal Microglial Activation in Poststroke Depression

Background and Purpose: Microglia play important role in poststroke depression (PSD), however, the exact mechanism was still unclear. The purpose of the study was to study the mechanism of microglial activation in PSD.Methods: 24 rats were randomly divided into three groups: the PSD group (n = 10), the poststroke (PS) group (n = 7), and the sham group (n = 7). Primary hippocampal microglia were isolated and cultured, and recombined LCN2 protein was used to stimulate the cultured microglia. The protein expression of Iba1, P38 MAPK and PP38 MAPK was analyzed by western blotting; the LCN2 expression was measured by RT-qPCR, the serum LCN2 level and the NO level were analyzed by ELISA.Results: Open field test scores (horizontal score, vertical score, and self-grooming score) and the serum LCN2 level were significantly decreased in the PSD group compared with the other two groups (P < 0.05). The serum LCN2 level was positively correlated with the horizontal score and negatively correlated with the self-grooming score in the open field test (P < 0.05). The relative protein level of Iba1 and the LCN2 mRNA level were significantly increased in the hippocampal region compared with other brain regions (P < 0.05), while the relative protein level of Iba1 and the LCN2 mRNA level were significantly increased in the PSD group compared with the other two groups (P < 0.05). The length, supernatant NO level, phagocytic ability and migration ability of LCN2-treated microglia were significantly increased compared with those of untreated microglia (P < 0.05). The relative protein levels of P38 MAPK and the PP38 MAPK significantly increased in hippocampal region in the PSD group and LCN2-treated hippocampal microglia (P < 0.05).Conclusion: Hippocampal microglia are activated during PSD; LCN2 may regulate hippocampal microglial activation by the P38 MAPK pathway in the process of PSD.

Garcinia Camobogia Extract Alters Anxiety, Sociability, and Dopamine Turnover in Male Swiss Albino Mice

Background: Obesity is a global concern, closely allied with somatic and psychosomatic disorders. Herbal drugs are available in modern medicine to treat obesity. Garcinia camobogia being used by so many people trying to lose weight produces various systemic side effects. The study was conducted to assess its effect on anxiety, sociability, and dopamine turnover in male mice. Methodology: Male Swiss albino mice of either were divided into three groups with seven mice in each group. Different groups were given distilled water (0.5ml p.o.) and Garcinia cambogia extract at two different doses (100mg/kg and 500 mg/kg p.o.). Effect of test drugs on anxiety was evaluated using open field test. Sociability and social novelty were evaluated using three chambers test. Results (mean ± standard deviation) were analyzed using one-way ANOVA test followed by Tukey’s test. Result: Garcinia cambogia extract significantly increased the time spent in the corners in the open field test, significantly reduced sociability and social novelty in the three chamber test, significantly reduced dopamine turnover and increased D2 receptor expression in ventral tegmental area. Conclusion: Garcinia cambogia extract have significant anxiogenic effect along with reduced sociability and social novelty in male mice. Moreover, these effects could be related to the altered dopamine turnover and D2 receptor expression in mice brain.

Effect of Short Time Exposure of Local ELF-MFs on Sleepiness Induced in Male Rats

Introduction: Lack of high-quality sleep causes serious side effects like anxiety and changes in plasma concentration of oxalate. The current study aimed to investigate the impact of local extremely low frequency magnetic fields (ELF-MFs) on inducing sleep (sleepiness) and anxiety in male rats. Methods: In this experimental study, 40 male rats were allocated in four groups (n=10). The ELF-MFs exposure (0, 10 and 18 Hz) was applied with intensity 200µT for three days (10 min/day). Sham-treated animal did not receive ELF-MF. Serum level of oxalic acid (OA) and sleepiness were measured both before first and after last exposure to ELF-MF or sham. Anxiety, sleepiness and OA were measured by using elevated plus maze, open-field test (OFT) and ELISA test, respectively. Results: Comparison of oxalate levels between before and after exposure to ELF-MF revealed that ELF-MF (10 Hz) decreased the serum level of oxalate (p<0.05). Comparison of the percent of open:closed arm entry (in elevated plus maze) between before and after exposure to ELF-MF revealed significant differences. Also, frequency, velocity and distance moved were decreased in the open-field test. Conclusion: Results of the present study demonstrated that ELF-MF with short time exposure may modulate the metabolism of OA and may modulate anxiety-like behavior or kind of induction of sleepiness in male rats.

Oxycodone decreases anxiety-like behavior in the elevated plus-maze test in male and female rats

The prescription opioid oxycodone is widely used for the treatment of pain in humans. Oxycodone misuse is more common among people with an anxiety disorder than those without one. Therefore, oxycodone might be misused for its anxiolytic properties. We investigated if oxycodone affects anxiety-like behavior in adult male and female rats. The rats were treated with oxycodone (0.178, 0.32, 0.56, or 1 mg/kg), and anxiety-like behavior was investigated in the elevated plus-maze test. Immediately after the elevated plus-maze test, a small open field test was conducted to determine the effects of oxycodone on locomotor activity. In the elevated plus-maze test, oxycodone increased the percentage of time spent on the open arms, the percentage of open arm entries, time on the open arms, open arm entries, and the distance traveled. The males treated with vehicle had a lower percentage of open arm entries than the females treated with vehicle, and oxycodone treatment led to a greater increase in the percentage of open arm entries in the males than females. Furthermore, the females spent more time on the open arms, made more open arm entries, spent less time in the closed arms, and traveled a greater distance than the males. In the small open field test, treatment with oxycodone did not affect locomotor activity or rearing. Sex differences were observed; the females traveled a greater distance and displayed more rearing than the males. In conclusion, oxycodone decreases anxiety-like behavior in rats, and oxycodone has a greater anxiolytic-like effect in males than females.