Preliminary Study: Effects of Social Instability Stress on Depressive Behaviours in Ovariectomised Rats

Background: Depression is one of the common post-menopausal symptoms. In addition to estrogen deiciency, social instability stress may contribute as an additional underlying factor in the development of depressive behaviour in females. Therefore, this study was aimed at examining the inluence of social instability stress on depressive behaviour in ovariectomized rats. Methods: The rats were divided into four groups (n = 5 per group); (i) sham-operated control without stress, (ii) sham-operated control with stress, (iii) ovariectomized without stress, and (iv) ovariectomized with stress. These rats were subjected to social instability stress procedures for 15 days prior to an enforced swimming test. Struggling, immobility, and swimming times were recorded promptly. Results: The results were analysed using the one-way analysis of variance (ANOVA) and a P value of < 0.05 was considered as signiicant. The mean durations of struggling, immobility, and swimming behaviour were signiicantly distinct among the four groups. Ovariectomized rats exhibited a substantial decrease in struggling and swimming behaviour, and an increase in immobility behaviour in comparison with the sham-operated controls (P < 0.05). Ovariectomized rats with stress displayed a supplementary decrease in struggling and swimming behaviour as well as an advanced increase in immobility behaviour, compared to sham-operated controls with or without stress (P < 0.05). Conclusion: In summary, these indings suggest that ovariectomized rats encountered an augmented amount of depressive behaviour following social instability stress

Dual role of dopamine D2-like receptors in the mediation of conditioned and unconditioned fear

AbstractA reduction of dopamine release or D2 receptor blockade in the terminal fields of the mesolimbic system, particularly the amygdala, clearly reduces conditioned fear. Similar D2 receptor antagonism in the neural substrates of fear in the midbrain tectum attenuates the processing of unconditioned aversive information. However, the implications of the interplay between opposing actions of dopamine in the rostral and caudal segments of the dopaminergic system are still unclear. Previous studies from this laboratory have reported the effects of dopaminergic drugs on behavior in rats in the elevated plus maze, auditory-evoked potentials (AEPs) recorded from the midbrain tectum, fear-potentiated startle, and conditioned freezing. These findings led to an interesting framework on the functional roles of dopamine in both anxiety and fear states. Dopamine D2 receptor inhibition in the terminal fields of the mesolimbic dopamine system generally causes anxiolytic-like effects, whereas the activity of midbrain substrates of unconditioned fear are enhanced by D2 receptor antagonists, suggesting that D2 receptor-mediated mechanisms play opposing roles in fear/anxiety processes, depending on the brain region under study. Dopamine appears to mediate conditioned fear by acting at rostral levels of the brain and regulate unconditioned fear at the midbrain level, likely by reducing the sensorimotor gating of aversive events

Tualang honey supplement improves memory performance and hippocampal morphology in stressed ovariectomized rats

Recently, our research team has reported that Tualang honey was able to improve immediate memory in postmenopausal women comparable with that of estrogen progestin therapy. Therefore the aim of the present study was to examine the effects of Tualang honey supplement on hippocampal morphology and memory performance in ovariectomized (OVX) rats exposed to social instability stress. Female Sprague-Dawley rats were divided into six groups: (i) sham-operated controls, (ii) stressed shamoperated controls, (iii) OVX rats, (iv) stressed OVX rats, (v) stressed OVX rats treated with 17�-estradiol (E2), and (vi) stressed OVX rats treated with Tualang honey. These rats were subjected to social instability stress procedure followed by novel object recognition (NOR) test. Right brain hemispheres were subjected to Nissl staining. The number and arrangement of pyramidal neurons in regions of CA1, CA2, CA3 and the dentate gyrus (DG) were recorded. Two-way ANOVA analyses showed significant interactions between stress and OVX in both STM and LTM test as well as number of Nissl-positive cells in all hippocampal regions. Both E2 and Tualang honey treatments improved both short-term and long-term memory and enhanced the neuronal proliferation of hippocampal CA2, CA3 and DG regions compared to that of untreated stressed OVX rat

Green synthesis of silver nanoparticles by tualang honey modulating Hippocampal glutathione in kainic acid-induced seizure in male rats

In recent years, green synthesis of nanoparticles using plant-mediated process has been an emerging research and development in the field of medicinal biotechnology. Tualang honey, a potential natural antioxidant medicinal agent, has been shown to protect against neurodegenerative disorders. Present study explored the ameliorative effects of silver nanoparticles (AgNPs) synthesized using Tualang honey on glutathione level following kainic acid (KA)-induced seizure in the rats' hippocampus. Sprague Dawley male rats (n=42) were randomly divided into seven groups such as control, AgNPs 10 mg,AgNPs50mg, KA alone, AgNPs 10 mg+KA, AgNPs 50 mg+KA and Topiramate+KA, and each group were pre-treated orally with either distilled water, AgNPs (10 mg/kg or 50 mg/kg) or Topiramate (40 mg/kg), respectively, five times at 12 h intervals. Saline or KA (15 mg/kg body weight) were injected subcutaneously 30 min after last oral treatment. All animals were sacrificed 24 h after KA injection and their hippocampus were harvested for determination the level of reduced glutathione (GSH), oxidized glutathione (GSSG) and GSH:GSSG ratio by using commercially available ELISA kits. The significant(p<0.05) decrease in the level of GSH in KA alone group was ameliorated by both doses of AgNPs pre-treatments. Meanwhile, the elevation of GSSG level in KA alone group was significantly(p<0.05)reduced by the pre-treatments of AgNPs 10 mg and Topiramate of KA-induced groups. Remarkably, only AgNPs 1 0+KA group was significantly (p<0.05) increases the GSH:GSSG ratio after KA induced. In conclusion, AgNPs showed potential protective effects by modulating the glutathione system in the rats hippocampus after KA induced

The ameliorative effects of Tualang honey mediated silver nanoparticles on hippocampal damages following kainic acid administration in male rats

Kainic acid (KA) was shown to be associated in the mechanism of excitotoxicity-induced neurodegeneration in the brain. Tualang honey (TH) was reported to have protection against neurodegeneration but no study has explored on its silver nanoparticles (THSN). Therefore, present study aimed to investigate the effects of THSN on glutathione status and hippocampal histology in KA-induced rats. Sprague-Dawley rats (n=42) were divided into seven groups such as control, THSN 10 mg, THSN 50 mg, KA alone, THSN 10 mg + KA, THSN 50 mg + KA and Topiramate + KA, and each group were pretreated orally with either distilled water, THSN (10 mg/kg or 50 mg/kg) or Topiramate (40 mg/kg), respectively, five times at 12 h intervals. Saline or KA (15 mg/kg body weight) were injected subcutaneously 30 min after last oral treatment. All animals were sacrificed 24 h post KA injection and the hippocampus was harvested for histological examination using cresyl violet staining. The reduced glutathione (GSH) and oxidized glutathione (GSSG) was determined using commercially available ELISA kits. The significant (p<0.05) decrease in the level of cresyl violet-positive cells in hippocampal CA3 in KA alone group was ameliorated by THSN (10 mg/kg) pretreatment group. Meanwhile, the KA induced reduction in GSH:GSSG ratio in KA alone group was significantly (p<0.05) increased by both doses of THSN pretreatments. In conclusion, THSN showed potential protective effects by improving the glutathione status and reduce hippocampal cells injury in the rats after KA induced

Tualang honey attenuates glutathione depletion in the rat hippocampus following kainic acid administration

Excitotoxicity mediated neurodegeneration by kainic acid (KA) was shown to cause oxidative stress in rats’ brains. Tualang honey (TH), a potential natural medicinal agent, was reported to have many therapeutic properties; however, its protection against neurodegenerative disorders was limited. This study aimed to investigate the protective effects of TH on glutathione levels following KA administration in the rats’ hippocampus. Sprague Dawley male rats (n=24) were randomly divided into four groups which are: (i) control, (ii) KA alone, (iii) TH + KA, and (iv) Topiramate (TPM) + KA, and each group was pre-treated orally with either distilled water, TH (1.0 g/kg) or Topiramate (40 mg/kg), respectively, five times at 12 h intervals. Saline or KA (15 mg/kg body weight) were injected subcutaneously 30 min after the last oral treatment. All animals were sacrificed 24 h after KA injection and their hippocampus was harvested to assay the level of reduced glutathione (GSH), oxidized glutathione (GSSG), and GSH:GSSG ratio by using commercially available ELISA kits. The result showed a significant (p<0.05) decrease in the level of GSH in the KA alone group and was improved by TH pretreatment. Meanwhile, the elevation of GSSG level in the KA-induced group was significantly (p<0.05) reduced by pre-treatments of TH and Topiramate. Remarkably, the pre-treatment of TH was significantly (p<0.05) increases the GSH:GSSG ratio after KA administration. In conclusion, TH showed potential protective effects to prevent oxidative stress-related consequences by attenuating the glutathione system in the rats’ hippocampus after KA administration

Mood and Memory Function in Ovariectomised Rats Exposed to Social Instability Stress

This study aims to compare the effects of social instability stress on memory and anxiety- and depressive-like behaviour between sham-operated controls and ovariectomised (OVX) rats. Forty adult female Sprague-Dawley rats (8 weeks old) were randomly divided into four groups,

Preliminary study on the effect of Tualang Honey and its silver nanoparticles on Kainic Acid-Induced memory deficits and oxidative damage in rat hippocampus

Kainic acid (KA) mediated excitotoxicity has been shown to cause memory impairment and oxidative stress in rats brain. The aim of this study was to investigate the effect of Tualang honey (TH) and its silver nanoparticles (THSN) on the KA-induced memory deficits and oxidative damage in rats’ hippocampus.Twenty-four adult male Sprague-Dawley rats were randomized into eight groups: (i) control, (ii) THSN (10mg/kg), (iii) THSN (50mg/kg), (iv) KA only, (v) KA+TH, (vi) KA+THSN (10mg/kg), (vii) KA+THSN (50mg/kg), and (viii) KA+Topiramate. Based on their respective groups, rats were pretreated orally with either distilled water, THSN (10 or 50 mg/kg body weight), Tualang honey (1.0 g/kg body weight), or Topiramate (40 mg/kg body weight), five times at 12 hours intervals. Saline or KA (15 mg/kg body weight) were injected subcutaneously 30 min after last oral treatment.Novel object recognition test (NORT) was performedfor memory assessment. The rats were sacrificed 24 hours post KA induction and hippocampus was harvested. Malondialdehyde (MDA) and superoxide dismutase (SOD) were measured using commercially available ELISA kits. The results showed that there was a trend of decreased in MDA level in both TH and THSN groups, however there were no significance difference. There wassignificantly increased level in SOD following pretreatment with TH and THSN groups compared to KA only group. Interestingly, these pretreatmentgroups also demonstrated enhanced memory as evidenced by significant increase in recognition index in NORT when compared to KA only group. In conclusion, this preliminary finding suggests that the pretreatment with TH and THSN might have potential role toimprove the memory and ameliorate oxidative stress in the KA-induced exitotoxicity rats. However, further study needs to be carried out to understand the precise mechanism

Stingless bee honey improves spatial memory in mice, probably associated with brain-derived neurotrophic factor (BDNF) and Inositol 1,4,5- triphosphate receptor type 1 (Itpr1) genes

This study was conducted to evaluate the effects of stingless bee honey (SBH) supplementation on memory and learning in mice. Despite many studies that show the benefits of honey on memory, reports on the nootropic effects of SBH are still lacking, and their underlying mechanism is still unclear. SBH is a honey produced by the bees in the tribe of Meliponini that exist in tropical countries. It features unique storage of honey collected in cerumen pots made of propolis. This SBH may offer a better prospect for therapeutic performance as the previous report identifies the presence of antioxidants that were greater than other honey produced by Apis sp. In this study, SBH was tested on Swiss albino mice following acute (7 days) and semichronic (35 days) supplementation. Experiments were then conducted using Morris water maze (MWM) behaviour analysis, RT-PCR for gene expression of mice striatum, and NMR for metabolomics analysis of the honey. Results indicate spatial working memory and spatial reference memory of mice were significantly improved in the honey-treated group compared with the control group. Improved memory consolidations were also observed in prolonged supplementation. Gene expression analyses of acutely treated mice demonstrated significant upregulation of BDNF and Itpr 1 genes that involve in synaptic function. NMR analysis also identified phenylalanine, an essential precursor for tyrosine that plays a role at the BDNF receptor. In conclusion, SBH supplementation for seven days at 2000 mg/kg, which is equivalent to a human dose of 162 mg/kg, showed strong capabilities to improve spatial working memory. And prolonged intake up to 35 days increased spatial reference memory in the mice model. The phenylalanine in SBH may have triggered the upregulation of BDNF genes in honey-treated mice and improved their spatial memory performance

The IntelliCage system: a review of its utility as a novel behavioral platform for a rodent model of substance use disorder

The use of animal models for substance use disorder (SUD) has made an important contribution in the investigation of the behavioral and molecular mechanisms underlying substance abuse and addiction. Here, we review a novel and comprehensive behavioral platform to characterize addiction-like traits in rodents using a fully automated learning system, the IntelliCage. This system simultaneously captures the basic behavioral navigation, reward preference, and aversion, as well as the multi-dimensional complex behaviors and cognitive functions of group-housed rodents. It can reliably capture and track locomotor and cognitive pattern alterations associated with the development of substance addiction. Thus, the IntelliCage learning system offers a potentially efficient, flexible, and sensitive tool for the high-throughput screening of the rodent SUD model