Behavior In Male Wistar Rats Research Articles

Effects of Cannabis sativa on the Neuromuscular System and Cognitive Behavior of Male Wistar Rats

This research investigates the influence of Cannabis sativa on the neuromuscular system and cognitive behavior of male Wistar rats. Twenty rats were randomly allocated into five groups, with Group 5 serving as the control and Groups 1 to 4 receiving oral doses of Cannabis sativa at concentrations of 100 mg/kg, 200 mg/kg, 400 mg/kg, and 800 mg/kg, respectively. The study employs various behavioral tests, including the Beam Walking Test, Morris Water Maze, Tail Suspension Test, Open-Field Test, and Hand Grip Test, to assess the effects of Cannabis on Wistar rats. Results from the Beam walking Test suggest that the control group (Group 5) demonstrated the best neuromuscular performance, with Group 3, (receiving 400 mg/kg), following closely. In the Morris Water Maze, Groups 1 and 5 exhibited superior results, while higher doses had a negative impact. Tail Suspension Test outcomes revealed that Group 5 displayed non-depressive behavior, while Group 4 exhibited signs of depression. The Hand Grip Test demonstrated longer duration for Groups 2 and 4, suggesting a positive impact on muscle strength compared to the control, on Open Field Test, Group 1 spent the most of the time at the center, indicating lower anxiety, whereas other groups displayed increased anxiety with higher Cannabis doses. The study highlights complex and dose-dependent effects of Cannabis on neuromuscular and cognitive parameters. Caution is advised in interpreting these findings, and further research is recommended to elucidate underlying mechanisms and explore a broader range of doses. Keywords: Cannabis sativa, cognitive function neuromuscular function

Pretreatment with 4-methylumbilliferon improves anxiety-like behaviors and memory impairment in stressed rats via modulation of neuronal cell death and oxidative stress

This work was done to investigate the ameliorating impact of 4-methylumbilliferon (4-MU) on spatial learning and memory dysfunction and restraint stress (STR)-induced anxiety-like behaviors in male Wistar rats and the underlying mechanisms. Thirty-two animals were assigned into 4 cohorts: control, 4-MU, STR, and STR+4-MU. Animals were exposed to STR for 4 h per day for 14 consecutive days or kept in normal conditions (healthy animals without exposure to stress). 4-MU (25 mg/kg) was intraperitoneally administered once daily to STR rats before restraint stress for 14 consecutive days. The behavioral tests were performed through Morris water maze tests and elevated-plus maze to examine learning/memory function, and anxiety levels, respectively. The levels of the antioxidant defense biomarkers (GPX, SOD) and MDA as an oxidant molecule in the brain tissues were measured using commercial ELISA kits. Neuronal loss or density of neurons was evaluated using Nissl staining. STR exposure could cause significant alterations in the levels of the antioxidant defense biomarkers (MDA, GPX, and SOD) in the prefrontal cortex and hippocampus, induce anxiety, and impair spatial learning and memory function. Treatment with 4-MU markedly reduced anxiety levels and improved spatial learning and memory dysfunction via restoring the antioxidant defense biomarkers to normal values and reducing MDA levels. Moreover, more intact cells with normal morphologies were detected in STR-induced animals treated with 4-MU. 4-MU could attenuate the STR-induced anxiety-like behaviors and spatial learning and memory dysfunction by reducing oxidative damage and neuronal loss in the prefrontal cortex and hippocampus region. Taken together, our findings provide new insights regarding the potential therapeutic effects of 4-MU against neurobehavioral disorders induced by STR.

Microstructure of the dentate gyrus and spontaneous alternation behaviour of male Wistar rats following Rauvolfia vomitoria and Gongronema latifolium extracts administration

Rauvolfia vomitoria (RV) and Gongronema latifolium (GL) are medicinal plants used for the local treatment of various health issues. Their activities on the brain motivated this investigation on the histology and immunohistochemistry of the dentate gyrus and spontaneous alternation behaviour (SAB) of adult Wistar rats following RV root bark and GL leaf extract administrations. Twenty young adult Wistar rats (130–160 g) were assigned into four groups: Group 1 served as the control (5 mL/kg of distilled water placebo), while the test groups 2–4 were, respectively, singly administered 200 of mg/kg of RV, 200 of mg/kg of GL, and their combination. The administrations were oral and lasted for seven days. A T-maze SAB test was carried out, and the animals were sacrificed immediately after ketamine hydrochloride intraperitoneal anaesthesia. Serial sections of the hippocampal region from perfused rat brains were stained with Cresyl fast violet and immunolabelled with neuronal nuclei (NeuN) for neurons and glial fibrillary acidic protein (GFAP) for astrocytes. Results indicated that SAB was significantly (p < 0.05) lower in the test groups. Histologically, Nissl was less distributed in the RV and GL-only groups but not in the combined group, while there was less NeuN positivity in the RV group, with the GL and RV + GL groups not affected. There was less positive GFAP expression in individual RV and GL groups, but not in the RV + GL combined group, all compared with the control. In conclusion, the combination of RV and GL did not improve SAB but modulated Nissl, NeuN, and GFAP expression in the dentate gyrus.

Pineapple (Ananas comosus) Ameliorates Depressant-like Behaviors in Rats Induced by Lipopolysaccharide

Background: Lipopolysaccharide (LPS) injection can lead to depression and mood disorders by reducing tryptophan availability through increased activity of the enzyme indoleamine 2,3-dioxygenase. Tryptophan, sourced from fruits such as pineapple (Ananas cosmosus), is vital for the body, especially the serotonergic system. Aim: This study aims to assess how pineapple pulp (PP) counters LPS-induced depressive behaviors in male Wistar rats. Methods: The experiment involved force-feeding PP for 28 days before LPS injection (0.5 mg/kg intraperitoneal [i.p.]) in 30 male Wistar rats, divided into five groups. Groups I (normal) and II (LPS control) received 15 ml aquadest/kg/day. Test Groups III, IV, and V were given varied doses of PP; low dose (3.75 ml/kg/day), medium dose (7.5 ml/kg/day), and high dose (15 ml/kg/day). At the study’s end, rats underwent the open field test (OFT) and the tail suspension test (TST). In addition, blood and brain samples were analyzed for neuroendocrine markers related to depression. Results: LPS triggers depressive symptoms, as evidenced by increased immobility time in the TST and altered behaviors indicative of anxiety in the OFT, especially in groups not receiving PP. This is followed by decreased serotonin levels in both plasma and brain when compared to groups given PP. In addition, higher corticosterone levels were observed in the LPS group than in the PP-treated group. Administering PP at 7.5 ml/kg/day for 28 days can alleviate the depressive effects induced by LPS injection. Conclusion: PP may have antidepressant properties, potentially by mitigating behaviors leading to depressive symptoms.

The role of labile iron on brain proteostasis; could it be an early event of neurodegenerative disease?

Iron deposits in the brain are a natural consequence of aging. Iron accumulation, especially in the form of labile iron, can trigger a cascade of adverse effects, eventually leading to neurodegeneration and cognitive decline. Aging also increases the dysfunction of cellular proteostasis. The question of whether iron alters proteostasis is now being pondered. Herein, we investigated the effect of ferric citrate, considered as labile iron, on various aspects of proteostasis of neuronal cell lines, and also established an animal model having a labile iron diet in order to evaluate proteostasis alteration in the brain along with behavioral effects. According to an in vitro study, labile iron was found to activate lysosome formation but inhibits lysosomal clearance function. Furthermore, the presence of labile iron can alter autophagic flux and can also induce the accumulation of protein aggregates. RNA-sequencing analysis further reveals the upregulation of various terms related to proteostasis along with neurodegenerative disease-related terms. According to an in vivo study, a labile iron-rich diet does not induce iron overload conditions and was not detrimental to the behavior of male Wistar rats. However, an iron-rich diet can promote iron accumulation in a region-dependent manner. By staining for autophagic markers and misfolding proteins in the cerebral cortex and hippocampus, an iron-rich diet was actually found to alter autophagy and induce an accumulation of misfolding proteins. These findings emphasize the importance of labile iron on brain cell proteostasis, which could be implicated in developing of neurological diseases.

Oral administration of resveratrol reduces oxidative stress generated in the hippocampus of Wistar rats in response to consumption of ethanol.

Chronic ethanol intake has been found to favor hippocampal deterioration and alter neuronal morphological maturation; resveratrol has been suggested as an antioxidant that may counteract these effects. The objective of this study was to analyze the effect of resveratrol on oxidative stress markers, endogenous antioxidant system in the hippocampus, and the behavior of male Wistar rats administered different concentrations of ethanol. The animals, at 3 months old, were randomly distributed into 11 study groups (n = 6/group), orally administered (5 days on, 2 days off) with water (control), ethanol (10, 20, 30, 40 or 50%), or ethanol (10, 20, 30, 40 or 50%) plus resveratrol (10 mg/Kg/day) for 2 months. Subsequently, the production of nitrites, malondialdehyde, and 4-hydroxy-alkenal (HNE) and the enzymatic activity of catalase and superoxide dismutase (SOD) were quantified. The levels of nitric oxide and lipid peroxidation products were significantly increased in each ethanol concentration and were statistically different compared to the control group; however, resveratrol significantly reduced oxidative stress caused by high ethanol concentration. The SOD and CAT did not present significant changes with respect to the controls in any of the study groups. In the different concentrations of ethanol used, GR increases significantly in the groups administered with resveratrol but not GPx. Resveratrol was shown to maintain the results similar to the control at most ethanol concentrations. Our results suggest that resveratrol prevents oxidative stress induced by ethanol in the hippocampus by decreasing cellular lipid peroxidation, but does not prevent the activation of catalase or SOD enzymes; however, allows glutathione to be kept active and in adequate concentrations in its reduced form and avoids alterations in the locomotor system.

Pterostilbene ameliorates type-2 diabetes mellitus – Induced depressive-like behavior by mitigating insulin resistance, inflammation and ameliorating HPA axis dysfunction in rat brain

One of the most serious mental health comorbidities associated with diabetes mellitus is depression. The occurrence is almost double in type 2 diabetes mellitus (T2DM) compared with the general population. Pterostilbene (PTE), a dimethylated analog of resveratrol, has been reported for significant neuroprotective, anti-inflammatory, hypolipidemic, hypoglycaemic and antioxidant effects. However, its effect on diabetes-induced depression-like behavior (DID) has not been studied.The current study aimed at studying the effects of PTE on depressive-like behavior in male Wistar rats with T2DM. It was induced by single dose administration of nicotinamide (NA) and streptozotocin (STZ). On day 21, forced swim test (FST) was conducted for the confirmation of DID. Rats demonstrating depressive-like behavior were treated with PTE (10, 20 and 40 mg/kg), metformin (MET; 500 mg/kg) and fluoxetine (FLX; 10 mg/kg) for 28 days, orally. At the end of the treatment, behavioral assessment for depression, blood glucose (BG) and lipid profile, oxidative stress markers, gene expression of Sirtuin 1 (SIRT1) and histopathological parameters were investigated. PTE significantly reduced weight loss and mitigated depressive-like behavior paradigms such as sucrose preference test (SPT), resident intruder test (RIT) and open field test (OFT). It significantly restored BG, lipid and liver profile, creatinine and antioxidant level. It Improved glucose tolerance, insulin resistance (IR) and reduced cortisol level as well as inflammatory markers. It showed improved morphology of the pancreas, brain, liver and kidney. Gene expression studies revealed that, PTE significantly increased SIRT1 expression. PTE by its virtue to maintain BG, reduced IR, amelioration of the HPA axis, anti-inflammatory, antioxidant activity and improvement of SIRT1 gene expression proved to be effective in the treatment of DID-like behavior in rats.

Vitamin C supplementation promotes locomotor and exploratory behaviors in male Wistar rats exposed to varying stress models.

Constant exposure to environmental stress has negative behavioral outcomes. Considering the inverse relationship between stress and Vitamin C intake, this study was aimed at investigating variable stress techniques and Vitamin C supplementation on exploratory/locomotor behaviors in male Wistar rats. Twenty-eight male Sprague-Dawley rats (100g-120g) were allotted into four groups (n=7). Control received 10ml/kg distilled water, group two received 100 mg/kg vitamin C, group three was exposed to different models of stress while group four was stressed alongside 100 mg/kg vitamin C. Vitamin C treatments were given orally for 2 weeks. Animals in groups 3 and 4 were stressed every other day with models such as multiple cage changes, exposure to noise, overnight strange objects, overnight wetting of beddings, and immobility. Explorative and locomotor activities were assessed with the open field test, novel object recognition test, and Y maze test using a Logitech camera and ANY-maze software to track the movement of the rats. Cortisol was assayed in the serum using Enzyme-linked Immuno Assay (ELISA) kit. Superoxide Dismutase, catalase, and lipid peroxidase; malondialdehyde (MDA) were also assayed in the serum. The results show that locomotor activities such as distance traveled, average speed, and time spent in the center square was significantly reduced by stress. These activities were improved with the intake of vitamin C compared with stress. Explorative activities such as locomoting around the environment, orientating towards novelty, and touching or sniffing novel objects were significantly increased in the rats on Vitamin C supplements and reduced in the stressed group. In the serum, cortisol level was significantly increased in rats exposed to stress and decreased with Vitamin C intake. Stress also significantly increased MDA and decreased SOD and CAT while vitamin C supplement decreased MDA and increased SOD and CAT. In conclusion, oral intake of vitamin C enhanced explorative/locomotor behavior and increased oxidative stress in rats exposed to different models of stress.

Binging from Food to Alcohol: A Sequential Interaction Between Binging Behaviors in Male Wistar Rats.

The development of excessive alcohol (ethanol) and/or highly palatable food self-administration is an essential task to elucidate the neurobiological mechanisms that underlie these behaviors. Previous work has highlighted that ethanol self-administration is modulated by both the induction of aversive states (i.e., stress or frustration) and by the concurrent availability of appetitive stimuli (e.g., food). In our protocol, rats are food deprived for three days until they reach 82%-85% of their ad libitum weight. After that, rats are exposed daily for 10 days to a brief binge or control eating experience with highly sugary and palatable food (i.e., the ingestion of 11.66 and 0.97 kcal/3 min, respectively), which is followed by a two-bottle-choice test (ethanol vs. water) in their home cages for 90 min. This model induces robust binge eating, which is followed by a selective increase in ethanol self-administration. Therefore, this protocol allows to study: a) behavioral and neurobiological factors related to binge eating, b) different stages of alcohol use, and c) interactions between the latter and other addictive-like behaviors, like binge eating.

Naloxone-induced Septal Neuromodulation of Hoarding Behavior in Male Wistar Rats

Abstract Background: Advances have been made in recognizing the neural mechanisms controlling ingestive behavior and maintaining energy balance. The interlinkage between opiate pathways, hoarding behavior, and body weight homeostasis suggests that a malfunction of the opioidergic brain may well have a role in the pathophysiology of obesity. The potential of opioid antagonists to influence food hoarding, a type of appetitive ingestive behavior, needs to be explored. Hence, this study was undertaken with the aim of assessing the effect of naloxone as a septal neuromodulator in the hoarding behavior of laboratory rats. Materials and Methods: Stereotaxic techniques were implemented on 20 adult male Wistar rats. For the experimental group (n = 10), naloxone was injected into the septal area. For the control group (n = 10), 0.9% of normal saline was injected into the septal region. Hoarding scores before and after the administration of the drugs were noted and statistically analyzed. Results: Naloxone showed a significant decrease (P < 0.001) in the food-hoarding scores (6.6 ± 4.2) as compared to baseline-hoarding scores (41.5 ± 14.39). However, the hoarding scores in the control group did not depict any significant change when measured before and after instillation of 0.9% normal saline. Conclusion: Intraseptal naloxone has modulatory activity in the septal network with inhibitory influence upon hoarding behavior.

Alternative use of suvorexant (Belsomra®) for the prevention of alcohol drinking and seeking in rats with a history of alcohol dependence.

Alcohol use disorder (AUD) is one of the most treatment-resistant medical conditions globally. The orexin (Orx) system regulates diverse physiological processes, including stress, and is a system of interest for the development of pharmaceuticals to treat substance use disorders, particularly AUD. The present study tested the ability of the dual orexin receptor antagonist suvorexant (SUV), marketed by Merck as Belsomra®, for the treatment of insomnia, to decrease alcohol self-administration and the stress-induced reinstatement of alcohol-seeking behavior in male Wistar rats with a history of alcohol dependence. Rats were trained to orally self-administer 10% alcohol (30 min/day for 3 weeks) and were either made dependent via chronic intermittent alcohol vapor exposure (14 h ON, 10 h OFF) for 6 weeks or exposed to air (non-dependent). Starting on week 7, the effect of SUV (0-20 mg/kg, p.o.) was tested on alcohol self-administration at acute abstinence (8 h after vapor was turned OFF) twice weekly. A separate cohort of rats that were prepared in parallel was removed from alcohol vapor exposure and then subjected to extinction training for 14 sessions. Once extinction was achieved, the rats received SUV (0 and 5 mg/kg, p.o.) and were tested for the footshock stress-induced reinstatement of alcohol-seeking behavior. Suvorexant at 5, 10, and 20 mg/kg selectively decreased alcohol intake in dependent rats. Furthermore, 5 mg/kg SUV prevented the stress-induced reinstatement of alcohol-seeking behavior in dependent rats only. These results underscore the significance of targeting the Orx system for the treatment of substance use disorders generally and suggest that repurposing SUV could be an alternative approach for the treatment of AUD.

Interaction of lithium and sleep deprivation on memory performance and anxiety-like behavior in male Wistar rats

Sleep plays a crucial role in the modulation of physiological and cognitive functions. Many studies have reported the impairment effect of sleep deprivation (SD) on cognitive functions such as learning and memory. On the other hand, lithium as one of the oldest drugs used for the treatment of psychiatric disorders, affects cognitive functions and mood state. In this study, we aimed to assess the effect of lithium, SD (for 24 h), and the interaction effect of SD and lithium, on memory function and anxiety-like behavior. The water box, the shuttle box, elevated plus maze, and the three-chamber paradigm test were used to evaluate rat’s behavior. Also, lithium was injected intraperitoneal at the doses of 10 and 20 mg/kg, for three consecutive days. The results showed that SD impaired passive avoidance memory and social interaction memory, and decreased anxiety-like behavior. Lithium also impaired passive avoidance memory and induced an anxiolytic effect, while it improved social interaction memory and reversed the impairment effect of SD on social interaction memory. In conclusion, we suggested that interaction effect of SD and lithium on the function of brain-derived neurotrophic factor (BDNF) and glycogen synthase kinase3-β (GSK3-β) may be involved in the modulation of cognitive functions. As a limitation of this research, it was declared that we did not evaluate the function of GSK3-β and BDNF in the brain of rats, especially in the hippocampus. We suggested conducting more studies focusing on the interaction of SD and lithium on the function of BDNF and GSK3-β, and on different cognitive functions.

Long-term variable photoperiod exposure impairs the mPFC and induces anxiety and depression-like behavior in male wistar rats

Long-term shift work can cause circadian misalignment, which has been linked to anxiety and depression. However, the associated pathophysiologic changes have not been described in detail, and the mechanism underlying this association is not fully understood. To address these points, we used a rat model of CM induced by long-term variable photoperiod exposure [L-VP] (ie, for 90 days). We compared the numbers of neurons, astrocytes, and dendritic spines; dendrite morphology; long-term potentiation (LTP), long-term depression (LTD) and paired-pulse ratio (PPR); expression of glutamate receptor [N-methyl-d-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)] subunits and brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC); and the anxiety and depression behaviors between rats in the circadian misalignment (CM) and circadian alignment (CA, with normal circadian rhythm) groups. The results showed that L-VP reduced the number of neurons and astrocytes in the mPFC and decreased the number of dendritic spines, dendrite complexity, LTP, LTD, PPR, and expression of glutamate receptors (GluR1, GluR2, GluR3, NMDAR2A, and NMDAR2B) and BDNF in the mPFC. L-VP also induced anxiety and depression-like behaviors, as measured by the open field test, elevated plus-maze, sucrose preference test, and forced swim test. These results suggest that CM induces a loss of neurons and astrocytes and synaptic damage in surviving pyramidal cells in the mPFC might be involved in the pathophysiology of anxiety and depression.

A comparative study of Caesalpinia bonduc (L.) Roxb. root extracts on sexual behaviour in male Wistar rats.

Caesalpinia bonduc is among the traditionally used plant in Benin, for its enhancement of male sexual activity. This study was undertaken to investigate the potential effect of C.bonduc root extracts on sexual behaviour of male Wistar rats. For that, thirty-six rats were allocated into six groups and orally treated with dimethyl sulfoxide (control), Sildenafil citrate (standard) and C.bonduc root extracts (hexane, ethyl acetate, ethanol and methanol) orally for twenty-eight days. Sexual behaviour parameters such as intromission frequency, intromission latency, mount latency and mount frequency were evaluated on day 0, 14 and 28. After the study completion, the body and reproductive organ weights as well as testicular histology and testosterone level were recorded. C.bonduc root extracts treatments had no significant effect on the body weight of rats. Enhancement in sexual behaviour was observed in ethanolic extract treated rats. An significant increase in mount frequency and intromission frequency as well as significant reduction in mount latency and intromission latency were noticed for ethanolic extract. The same extract caused an improvement in testosterone levels, relative testes weight and histological architecture. The findings demonstrate the aphrodisiac potential of C.bonduc root and lend support to the folkloric use as aphrodisiac.

Влияние запаха мужчин и женщин на поведение лабораторных крыс

The results of behavioral tests of laboratory animals are highly variable. Even within the same laboratory the results of the same test can differ significantly. We tested the effect of the experimenter’s smell — male and female — on the behavior of male Wistar rats. The smell donors were clinically healthy non-smoking, low-alcohol-consuming volunteers aged 20–21: four men, and four women in the luteal phase of the menstrual cycle. They wore cotton socks and T-shirts at night, which, in the morning, were sealed in plastic bags. The animals were tested on the same day. In the first experiment (n = 20), smell samples were placed in the center of the elevated zero maze. First, we tested naive animals, after 20 days in the presence of a male smell, and after another 20 days in the presence of a female smell. The presence of human body smells during testing increased the rats’ anxiety. A male smell had a greater effect than a female smell. In the second experiment (n = 29), the delayed effect of exposure to human smells was studied. The home cages were equipped with perforated plastic containers with fabric inside. They remained in the cages for one hour. During exposure to the smell, the animals were aroused, which was manifested in an intensive examination of containers and multiple agonistic contacts. Four hours later, increased anxiety was noted only after exposure to a female smell. The obtained data show that the results of behavioral tests on laboratory rats may depend, inter alia, on the sex of the experimenter.

<i>Ulva lactuca</i> Linnaeus Potentially Promotes Reproductive Indices and Depressive-like Behavior of Hypertriglyceridemia Male Wistar Rats (<i>Rattus norvegicus</i> Berkenhout, 1769)

Excessive consumption of fatty foods can lead to hyperlipidemia, which is often coupled with hypertriglyceridemia (HTG), a condition where blood plasma triglyceride (TG) levels elevated beyond normal levels. This condition may disturb physiological functions of the body, such as reproductive functions, and other physiological imbalances leading to chronic stress and depression. Ulva lactuca is a potential natural treatment for HTG, as it contains various nutrients to aid physiological functions. This seaweed also has high levels of Cd, which can increase depression. Therefore, research on the potential benefits of U. lactuca should be followed by an investigation of its health risks. This research aimed to examine the effects of HTG and treatment with U. lactuca on reproduction and depressive-like behavior of male Wistar rats (Rattus norvegicus Berkenhout, 1769). The data collected in this research include body weight, serum TG concentration, gonadosomatic index (GSI), serum testosterone concentration using competitive ELISA, and depressive-like behaviors assessed using the Forced Swim Test (FST) and Open Field Test (OFT). Data were analyzed using One-Way ANOVA followed by DMRT, independent- and paired-samples t-test, and Kruskal-Wallis H test with a significance value of α=0.05. Body weight, serum TG and testosterone concentration, GSI, and depressive-like behaviors were increased by the HTG condition. Ulva lactuca at the1500 mg/kg BW/day did not significantly affect body weight, testosterone concentration, and depressive-like behaviors of HTG rats. Meanwhile, this treatment significantly increased the GSI and depressive-like behaviors of healthy rats. These results suggest that Ulva lactuca treatment not only enhances gonad growth and development but also increases depressive-like behaviors.

Intrahippocampal Effects of Nickel Injection on the Affective and Cognitive Response in Wistar Rat: Potential Role of Oxidative Stress.

The present study focused on affective and cognitive behaviors in male Wistar rats, following direct and unique exposure to nickel chloride (NiCl2), as well as the possible involvement of oxidative stress. The rats were exposed to NiCl2 (300 μM), by intracerebral administration of 2 μL of this metal at the right hippocampus, using the stereotaxic approach. Five days after the surgery, a battery of behavioral tests was performed, including the open-field test (OFT) and elevated plus maze test (EPM) to assess the state of anxiety-like behavior and forced swimming test (FST) for depressive-like behavior. Y-maze and Morris Water Maze (MWM) were used to evaluate working memory and spatial learning. Thereafter, oxidative stress markers of the hippocampus were evaluated. The results confirm that NiCl2 exerts anxiogenic effects in both anxiety tests and depressogenic effects in the FST. In addition, MWM and Y-maze data show that NiCl2 causes memory and spatial learning disorders. The biochemical assay results showed that intrahippocampal injection of NiCl2 increased the levels of nitric oxide and lipid peroxidation (p < 0.001), while the activities of catalase and superoxide dismutase were significantly decreased in the hippocampus (p < 0.01). Overall, these results suggest that NiCl2 causes affective and cognitive disorders and oxidative stress in rats.

Psychobiotic Effects of Multi-Strain Probiotics Originated from Thai Fermented Foods in a Rat Model.

This work aimed to investigate the psychobiotic effects of six bacterial strains on the mind and behavior of male Wistar rats. The probiotic (PRO) group (n=7) were rats pre-treated with antibiotics for 7 days followed by 14-day probiotic administration, antibiotics (ANT) group (n=7) were rats treated with antibiotics for 21 days without probiotics. The control (CON) group (n=7) were rats that received sham treatment for 21 days. The six bacterial strains with probiotic properties were mostly isolated from Thai fermented foods; Pedicoccus pentosaceus WS11, Lactobacillus plantarum SK321, L. fermentum SK324, L. brevis TRBC 3003, Bifidobacterium adolescentis TBRC 7154 and Lactococcus lactis subsp. lactis TBRC 375. The probiotics were freeze-dried into powder (6×109 CFU/5 g) and administered to the PRO group via oral gavage. Behavioral tests were performed. The PRO group displayed significantly reduced anxiety level and increased locomotor function using a marble burying test and open field test, respectively and significantly improved short-term memory performance using a novel object recognition test. Antibiotics significantly reduced microbial counts in rat feces in the ANT group by 100 fold compared to the PRO group. Probiotics significantly enhanced antioxidant enzymatic and non-enzymatic defenses in rat brains as assessed using catalase activity and ferric reducing antioxidant power assay, respectively. Probiotics also showed neuroprotective effects with less pyknotic cells and lower frequency of vacuolization in cerebral cortex. This multi-strain probiotic formulation from Thai fermented foods may offer a potential to develop psychobiotic-rich functional foods to modulate human mind and behaviors.

The interaction effect of sleep deprivation and cannabinoid type 1 receptor in the CA1 hippocampal region on passive avoidance memory, depressive-like behavior and locomotor activity in rats

Increasing evidence shows the interaction effect of cannabinoids and sleep on cognitive functions. In the present study, we aimed to investigate the interaction effect of cannabinoids type 1 receptor (CB1r) in the CA1 hippocampal region and sleep deprivation (SD) on passive avoidance memory and depressive-like behavior in male Wistar rats. We used water box apparatus to induce total SD (TSD) for 24 h. The shuttle-box was applied to assess passive avoidance memory and locomotion apparatus was applied to assess locomotor activity. Forced swim test (FST) was used to evaluate rat’s behavior. ACPA (CB1r agonist) at the doses of 0.01, 0.001 and 0.0001 μg/rat, and AM251 (CB1r antagonist) at the doses of 100, 10 and 1 ng/rat were injected intra-CA1, five minutes after training via stereotaxic surgery. Results showed SD impaired memory. ACPA at the doses of 0.01 and 0.001 μg/rat impaired memory and at all doses did not alter the effect of SD on memory. AM251 by itself did not alter memory, while at lowest dose (1 ng/rat) restored SD-induced memory deficit. Both drugs induced depressive-like behavior in a dose-dependent manner. Furthermore, both drugs decreased swimming at some doses (ACPA at 0.0001 μg/rat, AM251 at 0.001 and 0.01 ng/rat). Also, ACPA at the highest dose increased climbing of SD rats. In conclusion, we suggest CB1r may interact with the effect of SD on memory. Additionally, cannabinoids may show a dose-dependent manner in modulating mood and behavior. Interestingly, CB1r agonists and antagonists may exhibit a similar effect in some behavioral assessments.

Effects of Glycine Receptors of the Medial Preoptic Nucleus on Sexual Behavior of Male Wistar Rats.

We studied the effect of bilateral microinjections of selective pharmacological agents modulating glycine receptor activity into the medial preoptic nucleus on sexual behavior of male Wistar rats. Application of the glycine receptor blocker strychnine (20 μM, 2 μl) led to a significant inhibition of both appetitive and consummatory components of sexual behavior, whereas stimulation with glycine (1 mM and 50 μM, 2 μl) had no significant effect.