Locomotor Activity In Rats Research Articles

Circadian Rhythms of Body Temperature and Locomotor Activity in Spontaneously Hypertensive Rats under Frequent Changes in Light Conditions.

Changes in lighting accompany modern urbanization trends and can lead to various pathologies based on circadian disturbances. In this study, we assessed the changes in the circadian rhythm of core body temperature (Tcore) and locomotor activity of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) following exposure to different lighting conditions: extended light phase of the day (16 h-8 h, 20 h-4 h, 24 h-0 h), light pollution, monochromatic light, and bright light therapy. The telemetry data was collected after experimental lighting conditions during periods with standard lighting (12 h of light and 12 h of darkness) and was processed using linear and cosinor analysis. The daily rhythms of rats' parameters persisted in accordance with the standard lighting regime. Tcore changes were observed in both groups compared to the initial period: in WKY, a decrease in Tcore during the darkness and an increase during the light; in SHR, the opposite trend, with Tcore increased during the darkness and decreased during the light phase of the day. A relationship between Tcore and activity was observed with weak correlation. WKY exhibited more pronounced signs of adaptive variation and desynchronization compared to SHR, which could be associated with a wider range of functional capabilities of the organism without cardiovascular pathology.

Design and evaluation of magnetic-targeted bilosomal gel for rheumatoid arthritis: flurbiprofen delivery using superparamagnetic iron oxide nanoparticles.

The study aimed to systematically enhance the fabrication process of flurbiprofen-loaded bilosomes (FSB) using Quality by Design (QbD) principles and Design of Experiments (DOE). The objective was to develop an optimized formulation with improved entrapment efficiency and targeted drug delivery capabilities. The optimization process involved applying QbD principles and DOE to achieve the desired formulation characteristics. Superparamagnetic iron oxide nanoparticles (SPIONs) were incorporated to impart magnetic responsiveness. The size, entrapment efficiency, morphology, and in vitro release patterns of the FSB formulation were evaluated. Additionally, an in situ forming hydrogel incorporating FSB was developed, with its gelation time and drug release kinetics assessed. In vivo studies were conducted on osteoarthritic rats to evaluate the efficacy of the FSB-loaded hydrogel. The optimized FSB formulation yielded particles with a size of 453.60nm and an entrapment efficiency of 91.57%. The incorporation of SPIONs enhanced magnetic responsiveness. Morphological evaluations and in vitro release studies confirmed the structural integrity and sustained release characteristics of the FSB formulation. The in situ forming hydrogel exhibited a rapid gelation time of approximately 40 ± 1.8s and controlled drug release kinetics. In vivo studies demonstrated a 27.83% reduction in joint inflammation and an 85% improvement in locomotor activity in osteoarthritic rats treated with FSB-loaded hydrogel. This comprehensive investigation highlights the potential of FSB as a promising targeted drug delivery system for the effective management of osteoarthritis. The use of QbD and DOE in the formulation process, along with the integration of SPIONs, resulted in an optimized FSB formulation with enhanced entrapment efficiency and targeted delivery capabilities. The in situ forming hydrogel further supported the formulation's applicability for injectable applications, providing rapid gelation and sustained drug release. The in vivo results corroborate the formulation's efficacy, underscoring its potential for improving the treatment of osteoarthritis.

Церебропротекторное действие нового аналога халкона при экспериментальной черепно-мозговой травме. Фокус на митохондриальный биогенез и нейровоспаление

INTRODUCTION: Currently, the treatment of traumatic brain injuries requires a comprehensive approach which includes, among other things, the use of drugs possessing cerebroprotective activity. As a rule, the action of cerebral protectors is concentrated on separate pathophysiological mechanisms of brain damage, for example, the mitochondrial dysfunction. AIM: To study the effect of a new chalcone analogue on changes in the processes of mitochondrial biogenesis and neuroinflammation in rats with experimental traumatic brain injury. MATERIALS AND METHODS: In the work, rats of Wistar line were used in whom a traumatic brain injury was modeled by a single exposure of the parietal region of the skull to a freely falling weight. The studied compound and the comparison drug, choline alfoscerate, were introduced orally within 7 days after injury, at doses of 50 mg/kg and 150 mg/kg, respectively. The behavioral reactions of the animals were evaluated in the ‘open field’ test. The intensity of neuroinflammation was determined by changes in the concentrations of IL-1β, IL-6 and TNF-α in the brain tissue. The markers of mitochondrial biogenesis were changes in the activity of succinate dehydrogenase and cytochrome c oxidase. RESULTS: In the course of the work, it was found that the use of a new chalcone analogue in conditions of experimental traumatic brain injury facilitates an increase in locomotor and exploratory activity in rats, as well as reduces the level of anxiety. With the introduction of the studied compound, a decrease in the intensity of neuroinflammation reactions was observed, as evidenced by a decrease in the content of IL-1β by 58.8% (p < 0.05), IL-6 by 55.0% (p < 0.05) and TNF-α by 50.7% (p < 0.05) compared with untreated animals. The activity of succinate dehydrogenase and cytochrome c oxidase increased by 63.6% (p < 0.05) and 27.6% (p < 0.05), respectively, when using the studied chalcone analogue. To note, the activity of enzymatic markers of mitochondrial biogenesis in rats treated with chalcone analogue was higher than in animals who were introduced choline alfoscerate. CONCLUSIONS: The study showed for prospects of further investigation of a new chalcone analogues as a complex cerebroprotective agent for treatment of sequelae of a traumatic brain injury.

Elucidation for the pharmacological effects and mechanism of Shen Bai formula in treating myocardial injury based on energy metabolism and serum metabolomic approaches

Ethnopharmacological relevanceShen Bai formula (SBF) is a proven effective traditional Chinese medicine for treating viral myocarditis (VMC) sequelae in clinic, and myocardial injury is the pathological basis of VMC sequelae. However, the pharmacological action and mechanism of SBF have not been systematically elucidated. Aim of the studyIn present research, the doxorubicin-induced myocardial injury rat model was used to evaluate the efficacy of SBF, and energy metabolism and metabolomics approaches were applied to elucidate the effects of SBF on myocardial injury. Materials and methodsThrough energy metabolism measurement system and UPLC-Q-TOF-MS/MS oriented blood metabolomics, directly reflected the therapeutic effect of SBF at a macro level, and identified biomarkers of myocardial injury in microcosmic, revealing its metabolomic mechanism. ResultsResults showed that SBF significantly improved the electrocardiogram (ECG), heart rate (HR), extent of myocardial tissue lesion, and ratio of heart and spleen. In addition, the serum levels of AST, CK, LDH, α-HBDH, cTnI, BNP, and MDA decreased, whereas SOD and ATP activity and content increased. Moreover, SBF increased locomotor activity and basic daily metabolism in rats with myocardial injury, restoring their usual level of energy metabolism. A total of 45 potential metabolomic biomarkers were identified. Among them, 44 biomarkers were significantly recalled by SBF, including representative biomarkers arachidonic acid (AA), 12-HETE, prostaglandin J2 (PGJ2), 15-deoxy-Δ-12,14-PGJ2, 15-keto-PGE2, 15(S)-HPETE, 15(S)-HETE, 8,11,14-eicosatrienoic acid and 9(S)-HODE, which involved AA metabolism, biosynthesis of unsaturated fatty acids and linoleic acid metabolism. ConclusionWe successfully replicated a myocardial injury rat model with the intraperitoneal injection of doxorubicin, and elucidated the mechanism of SBF in treating myocardial injury. This key mechanism may be achieved by targeting action on COX, Alox, CYP, and 15-PGDH to increase or decrease the level of myocardial injury biomarker, and then emphatically interven in AA metabolism, biosynthesis of unsaturated fatty acids and linoleic acid metabolism, and participate in regulating purine metabolism, sphingolipid metabolism, primary bile acid biosynthesis, and steroid hormone synthesis.

Contemporary comprehensive approaches to assessing the effectiveness of experimental model of neurodegenerative disorders with cognitive status changes

Aim of the study was to characterize the locomotor and cognitive aspects of the behavior of experimental rats under intracerebroventricular colchicine administration in the open field test and the 8-arm radial maze, as well as identify a set of behavioral features of experimental animals that emerged during the study.
 Materials and methods. The study was conducted in two stages on 20 male Wistar rats aged 10–11 months. The first stage involved assessment of initial locomotor activity and cognitive functions in all intact rats. At the next stage, the rats were divided into two experimental groups (n = 10): the first group with intracerebroventricular injection of physiological NaCl solution, and the second group with intracerebroventricular injection of colchicine. In 14 days after the surgery, repeated recording of locomotive and cognitive activity indicators was performed.
 Results. The locomotor activity characteristics did not statistically differ between the animals before the surgical procedures and the rats of the first group. However, in the second group, the activity indicators were significantly higher than in the respective pre-surgery rats. In the intergroup comparison of the rats that entered the second stage of the experiment, it was found that among all the investigated parameters, only the indicator of high activity duration was significantly higher in the second group compared to the first group. At the same time, the animals in the second group showed significant cognitive impairments compared to the first group, as indicated by significantly lower memory index values, the number of correct entries into the maze arms, and a significantly longer time to make the first correct entry into the maze arm.
 Conclusions. Intracerebroventricular administration of colchicine to experimental rats is accompanied by increased locomotor activity and impairment of cognitive functions. The administration of a physiological solution is not accompanied by a statistically significant increase in locomotor activity, but it demonstrates a clear tendency to increase, which may indicate a certain influence of the procedure itself. The applied pharmacological model of neurodegeneration with subsequent comprehensive assessment of animal behavior in an open field and an 8-arm radial maze is legitimate and can be used to study the early development of neuroinflammation, neuroapoptosis, and synaptogenesis disorders in the experiment.

NEUROPROTECTIVE EFFECT OF PALIPERIDONE IN LPS INDUCED ANIMAL MODEL OF AD

AbstractBackgroundAlzheimer’s disease is a progressive neurological condition, that impairs cognition and memory. Extracellular beta‐amyloid plaques and intracellular neurofibrillary tangle formation are the two hallmarks while cognitive decline, neurotransmitter deficit, neuroinflammation, mitochondrial dysfunction, decreased cerebral glucose uptake, and oxidative stress has been known to contribute to the pathogenesis of AD. The present study was designed to investigate the neuroprotective potential of Paliperidone on intracerebroventricular (i.c.v.) Lipopolysaccharide‐induced experimental dementia of Alzheimer’s type.MethodLPS was administered by the i.c.v route on 1st day of the study in rats. Paliperidone was administered (1mg/Kg and 2mg/kg/day i.p) from the 1st to 21st day in LPS‐infused rats. Morris water maze, open‐field test, and object recognition parameters were used to assess learning, memory, behavioral changes and locomotor activity in rats. LPS infusion rapidly causes neuroinflammation and oxidative‐nitrosative stress.ResultThese markers were determined in the cortical and hippocampal brain regions of rats. While paliperidone treatment attenuates the LPS‐induced behavioral and biochemical abnormalities in rats by reducing levels of Malondialdehyde (MDA), reduced glutathione (GSH), and increasing levels of catalase. The neurodegeneration in Hippocampus and cortex regions was observed through histopathological examination. The observed cognitive improvement following paliperidone in LPStreated rats may be due to its antioxidant and anti‐inflammatory activity and restoration of cholinergic functions.ConclusionOur results suggest the therapeutic potential of paliperidone in cognitive disorders such as AD. However, more investigations are required to evaluate the potential of paliperidone in boosting memory and cognition and preventing neuronal damage.

Acute toxicity study of the isomeric mixture of alpha and beta amyrin from Protium heptaphyllum (Aubl.) Marchand

The isomeric mixture of alpha and beta amyrin (AMY), present in the resin of Protium heptaphyllum, is popularly used as anti-inflammatory and anti-ulcer. The literature has been demonstrating pharmacological activities of these triterpenes in the central and peripheral nervous systems, and in the gastrointestinal and immunological systems. This study traces a toxicological profile of amyrin, aiming to provide information that may clarify its safety. Nine female Wistar rats (170 to 200 g) were divided into three groups of three animals each (control, amyrin 300 and amyrin 2000 mg kg-1, p.o.), which were evaluated by protocols preconized by the Organization for Economic Co-operation and Development (OECD). Open field Test and Malone Hippocratic Screening Scale were performed. AMY, mostly at 2000 mg kg-1, reduced the number of crossings by 57% vs. saline (22.67 ± 2.40) and the number of rearing by 53% vs. saline (42.67 ± 2.96), but increased the number of grooming by 26% vs. saline (1.66 ± 0.33). AMY (2000 mg kg-1) increased the serum glucose by 77% vs. saline (126.70 ± 4.33 mg dL-1), triglycerides by 50% vs. saline (78.67 ± 2.18 mg dL-1) and uric acid by 65% vs. saline (0.73 ± 0.03 mg dL-1). AMY induced vascular congestion and hemorrhage in the liver, spleen and cerebral cortex. Renal changes (cellular damage, inflammatory infiltrate, tubular protein deposition and glomeruli atrophy) were also seen. In conclusion, AMY decreased rat locomotor activity, caused minor biochemical changes, and altered the morphology of the kidney. The present study may contribute to deepen the knowledge about the safety of AMY, aiming the development of a novel pharmacological product.

The Impact of Heroin Self-Administration and Environmental Enrichment on Ventral Tegmental CRF1 Receptor Expression.

There is a strong link between chronic stress and vulnerability to drug abuse and addiction. Corticotropin releasing factor (CRF) is central to the stress response that contributes to continuation and relapse to heroin abuse. Chronic heroin exposure can exacerbate CRF production, leading to dysregulation of the midbrain CRF-dopamine-glutamate interaction. Here we investigated the role of midbrain CRF1 receptors in heroin self-administration and assessed neuroplasticity in CRF1 receptor expression in key opioid addiction brain regions. Infusions of antalarmin (a CRF1 receptor antagonist) into the ventral tegmental area (VTA) dose dependently reduced heroin self-administration in rats but had no impact on food reinforcement or locomotor activity in rats. Using RNAscope in situ hybridization, we found that heroin, but not saline, self-administration upregulated CRF1 receptor mRNA in the VTA, particularly on dopamine neurons. AMPA GluR1 and dopamine reuptake transporter mRNA in VTA neurons were not affected by heroin. The western-blot assay showed that CRF1 receptors were upregulated in the VTA and nucleus accumbens. No significant changes in CRF1 protein expression were detected in the prefrontal cortex, insula, dorsal hippocampus, and substantia nigra. In addition, we found that 15 days of environmental enrichment implemented after heroin self-administration does not reverse upregulation of VTA CRF1 receptor mRNA but it downregulates dopamine transporter mRNA. Overall, these data suggest that heroin self-administration requires stimulation of VTA CRF1 receptors and upregulates their expression in brain regions involved in reinforcement. Such long-lasting neuroadaptations may contribute to continuation of drug use and relapse due to stress exposure and are not easily reversed by EE exposure.

Comorbidity of cardiorespiratory and locomotor dysfunction following cervical spinal cord injury in the rat.

Cervical spinal cord injury interrupts supraspinal pathways innervating thoracic sympathetic preganglionic neurons and results in cardiovascular dysfunction. Both respiratory and locomotor functions were also impaired due to damages of motoneuron pools controlling respiratory and forelimb muscles, respectively. However, no study has investigated autonomic and somatic motor functions in the same animal model. The present study aimed to establish a cervical spinal cord injury model to evaluate cardiorespiratory response and locomotor activity in unanesthetized rats. Cardiovascular response and respiratory behavior following laminectomy or cervical spinal contusion were measured using noninvasive blood pressure analyzer and plethysmography systems, respectively. Locomotor activity was evaluated by an open-field test and a locomotor rating scale. The results demonstrated that mean arterial blood pressure and heart rate were significantly reduced in contused rats compared with uninjured rats at the acute injured stage. Tidal volume was also significantly reduced during the acute and subchronic stages. Moreover, locomotor function was severely impaired, evidenced by decreasing moving ability and locomotor rating scores from the acute to chronic injured stages. Retrograde neurotracer results revealed that cervical spinal cord injury caused a reduction in number of phrenic and triceps motoneurons. Immunofluorescence staining revealed a significant attenuation of serotonergic, noradrenergic, glutamatergic, and GABAergic fibers innervating the thoracic sympathetic preganglionic neurons in chronically contused rats. These results revealed the pathological mechanism underlying the comorbidity of cardiorespiratory and locomotor dysfunction following cervical spinal cord injury. We proposed that this animal model can be used to evaluate the therapeutic efficacy of potential strategies to improve different physiological functions.NEW & NOTEWORTHY The present study establishes a preclinical rodent model to comprehensively investigate physiological functions under unanesthetized condition following cervical spinal cord contusion. The results demonstrated that cervical spinal cord contusion is associated with impairments in cardiovascular, respiratory, and locomotor function. Respiratory and forelimb motoneurons and neurochemical innervations of sympathetic preganglionic neurons were damaged following injury. This animal model can be used to evaluate the therapeutic efficacy of potential strategies to improve different physiological functions.

Blue light exposure-dependent improvement in robustness of circadian rest-activity rhythm in aged rats.

The aging effects on circadian rhythms have diverse implications including changes in the pattern of rhythmic expressions, such as a wide fragmentation of the rhythm of rest-activity and decrease in amplitude of activity regulated by the suprachiasmatic nucleus (SCN). The study of blue light on biological aspects has received great current interest due, among some aspects, to its positive effects on psychiatric disorders in humans. This study aims to evaluate the effect of blue light therapy on the SCN functional aspects, through the evaluation of the rest-activity rhythm, in aging rats. For this, 33 sixteen-months-old male Wistar rats underwent continuous records of locomotor activity and were exposed to periods of 6 hours of blue light during the first half of the light phase (Zeitgeber times 0-6) for 14 days. After this, the rats were maintained at 12h:12h light:dark cycle to check the long-term effect of blue light for 14 days. Blue light repeated exposure showed positive effects on the rhythmic variables of locomotor activity in aged rats, particularly the increase in amplitude, elevation of rhythmic robustness, phase advance in acrophase, and greater consolidation of the resting phase. This effect depends on the presence of daily blue light exposure. In conclusion, our results indicate that blue light is a reliable therapy to reduce circadian dysfunctions in aged rats, but other studies assessing how blue light modulates the neural components to modulate this response are still needed.

The effect of photoperiodic stress on anxiety-like behaviors, learning, memory, locomotor activity and memory consolidation in rats

The effect of photoperiodic stress on anxiety-like behaviors, learning, memory, locomotor activity and memory consolidation in rats

Estradiol enhances the mirtazapine effects on the expression of cocaine-induced locomotor sensitization in female rats.

Epidemiological studies have mentioned that cocaine use disorder (CUD) has increased in the last decade among women; these show endocrine and reproductive disorders and a high propensity to stress and depression disorders. Mirtazapine-a tetracyclic antidepressant-decreases cocaine-induced locomotor activity and locomotor sensitization in male rats. The objective of this study was to evaluate if estradiol alters the efficacy of mirtazapine to decrease cocaine-induced locomotor activity in sham and ovariectomized female rats. Three hundred and twenty adult female Wistar rats were assigned to three experimental protocols. For experiments, 1-3, female rats were daily dosed with 10 mg/kg of cocaine during the 10 days of induction and expression of locomotor sensitization. During drug withdrawal (30 days), cocaine was withdrawn and the groups received daily mirtazapine, estradiol, or saline. In addition, the females underwent sham or ovariectomy surgery. Tamoxifen was administered during the antagonism phase. After each administration, locomotor activity for each animal was recorded for 30 min in activity chambers. The dosage of mirtazapine reduces estradiol-induced enhancement in cocaine-dependent locomotor activity during the expression of locomotor sensitization in sham and ovariectomized female rats. As well as they showed that estradiol co-dosed with mirtazapine enhances the efficacy of mirtazapine to decrease cocaine-induced locomotor activity. Finally, tamoxifen enhanced the estradiol and mirtazapine-induced decrease in the cocaine motor effect in female rats. Mirtazapine may be considered an effective therapeutic option for the treatment of CUD in women, even in those who are on hormonal treatment or antidepressant therapy with estradiol.

The rostromedial tegmental nucleus RMTg is not a critical site for ethanol-induced motor activation in rats.

Opioid drugs indirectly activate dopamine (DA) neurons in the ventral tegmental area (VTA) through a disinhibition mechanism mediated by mu opioid receptors (MORs) present both on the GABA projection neurons located in the medial tegmental nucleus/tail of the VTA (RMTg/tVTA) and on the VTA GABA interneurons. It is well demonstrated that ethanol, like opioid drugs, provokes VTA DA neuron disinhibition by interacting (through its secondary metabolite, salsolinol) with MORs present in VTA GABA interneurons, but it is not known whether ethanol could disinhibit VTA DA neurons through the MORs present in the RMTg/tVTA. The objective of the present study was to determine whether ethanol, directly microinjected into the tVTA/RMTg, is also able to induce VTA DA neurons disinhibition. Disinhibition of VTA DA neurons was indirectly assessed through the analysis of the motor activity of rats. Cannulae were placed into the tVTA/RMTg to perform microinjections of DAMGO (0.13 nmol), ethanol (150 or 300 nmol) or acetaldehyde (250 nmol) in animals pre-treated with either aCSF or the irreversible antagonist of MORs, beta-funaltrexamine (beta-FNA; 2.5 nmol). After injections, spontaneous activity was monitored for 30 min. Neither ethanol nor acetaldehyde directly administered into the RMTg/tVTA were able to increase the locomotor activity of rats at doses that, in previous studies performed in the posterior VTA, were effective in increasing motor activities. However, microinjections of 0.13 nmol of DAMGO into the tVTA/RMTg significantly increased the locomotor activity of rats. These activating effects were reduced by local pre-treatment of rats with beta-FNA (2.5 nmol). The tVTA/RMTg does not appear to be a key brain region for the disinhibiting action of ethanol on VTA DA neurons. The absence of dopamine in the tVTA/RMTg extracellular medium, the lack of local ethanol metabolism or both could explain the present results.

Subchronic exposure to Tamoxifen modulates the hippocampal BDNF/ERK/Akt/CREB pathway and impairs memory in intact female rats

Tamoxifen (TAM), a Selective Estrogen Receptor Modulator (SERM), is commonly used to treat and prevent breast cancer. Memory impairment has been noticed in patients who experience hormone therapy in the case of TAM and other SERMs. Animal studies that mimic the TAM longer exposure effects are needed to better elucidate the adverse effects of continuous treatment in humans. This study evaluated the effects of TAM subchronic administration on the memory performance and hippocampal neural plasticity of intact female Wistar rats. Animals were treated intragastrically with TAM (0.25 and 2.5 mg/kg) for 59 days. The rats were subjected to the Object Location Test (OLT) and Object Recognition Test (ORT) to evaluate memory performance. After euthanasia, the hippocampus samples were excised and the protein levels of the BDNF/ERK/Akt/CREB pathway were evaluated. The rat's locomotor activity and hippocampal TrkB levels were similar among the experimental groups. TAM at both doses reduced the memory performance of female rats in the OLT and short-term memory of ORT, and impaired hippocampal levels of mBDNF, proBDNF, and pCREB/CREB. TAM only at the dose of 2.5 mg/kg reduced the memory performance of rats in the long-term memory of ORT and hippocampal pERK/ERK and pAkt/Akt ratios. TAM subchronic administration induced amnesic effects and modulated the hippocampal BDNF/ERK/Akt/CREB pathway in intact young adult female Wistar rats.

Spinal Cathepsin S promotes visceral hypersensitivity via FKN/CX3CR1/p38 MAPK signaling pathways.

Irritable bowel syndrome (IBS) is one of the typical representatives of chronic functional visceral pain that lacks effective treatment. Recently, attention has been given to the role of microglia in IBS, particularly the activation of spinal microglia and the subsequent release of Cathepsin S (Cat S), a proteolytic enzyme. However, the specific role of spinal Cat S in IBS remains to be elucidated. The purpose of this study is to investigate the mechanisms underlying the regulation of visceral hypersensitivity in IBS-like rats by Cat S. An IBS-like rat model was developed, and visceral sensitivity was tested via the electromyographic (EMG) response to colorectal distention (CRD) and pain threshold. Western blot and immunofluorescence were used to examine the expressions of proteins. The effects of inhibitors or neutralizing antibodies on visceral pain and the downstream molecular expressions were detected. The open-field test was performed to evaluate locomotor activity and anxiety-like behaviors in rats. We discovered that spinal Cat S was upregulated and colocalized with microglia in IBS-like rats. Treatment with LY3000328, a selective inhibitor of Cat S, dose-dependently down-regulated EMG amplitude and Fractalkine (FKN) expression, indicating that Cat S regulated visceral hypersensitivity via activating FKN in IBS-like rats. Furthermore, the expressions of FKN, CX3CR1, and p-p38 MAPK were elevated in IBS-like rats whereas inhibition of these molecules could alleviate visceral pain. Moreover, pharmacological inhibitor experiments suggested the activation of CX3CR1 by FKN facilitated p38 MAPK phosphorylation, which in turn promoted Cat S expression in IBS-like rats. Neonatal adverse stimulation might enhance the expression of spinal microglial Cat S, thereby activating the FKN/CX3CR1/p38 MAPK pathway and lead to visceral hypersensitivity in IBS-like rats. As a selective inhibitor of Cat S, LY3000328 could become a potential therapeutic option for IBS.

Study of Central Nervous System Depressant and Behavioral Activity of Ethanolic Extract of Clitoria Annuain Albino Rats

Objective: The objective was to evaluate depressant effects on central nervous system (CNS) and behavioral effects of ethanol extract of clitoria annua and to find the phytochemical responsible for these activities with possible mode of action. Materials & Method: The central nervous system (CNS) depressant activity of C. annua was evaluated by the classical models of depression as Rota rod method, Actophotometer test, tail suspension, and thiopental sodium induced sleeping time tests in Rat. The Rats were divided into Normal, Standard, and two test groups containing five rats each. The test groups received extract at the doses of 200, and 400 mg/kg body weight orally where as the Normal group received distilled water (0.1 ml/mice, p.o.). Diazepam (2 mg/kg, i.p.) was used as standard drug. Results: It is clear that the plant extract significantly decreased the locomotor activity of rats in Rota rod method and Actophotometer test when compared to the normal (p < 0.05). It is observed that the extract showed significantly (p < 0.05) increased in immobility time in tail suspension test in mice. In addition, the extract produced prolongs the sleeping time with onset of action in contrast to the normal group. Conclusions: The present work depicts the evaluation of possible CNS depressant activity of C. annua in mice models. EECA can be a safe and effective approach/alternative for the treatment of number of CNS depressant disorders. More extensive study is required to fractionate, purify, and identify the exact mechanism of action CNS Depressant activity present in ethanolic extract of Clitoria annua with its active ingredients.

Intranasal cerium oxide nanoparticles improves locomotor activity and reduces oxidative stress and neuroinflammation in haloperidol-induced parkinsonism in rats.

Introduction: Cerium oxide nanoparticles (CONPs) have been investigated for their therapeutic potential in Parkinson's disease (PD) due to their potent and regenerative antioxidant activity. In the present study, CONPs were used to ameliorate the oxidative stress caused by free radicals in haloperidol-induced PD in rats following intranasal administration. Method: The antioxidant potential of the CONPs was evaluated in vitro using ferric reducing antioxidant power (FRAP) assay. The penetration and local toxicity of the CONPs was evaluated ex-vivo using goat nasal mucosa. The acute local toxicity of intranasal CONPs was also studied in rat. Gamma scintigraphy was used to assess the targeted brain delivery of CONPs. Acute toxicity studies were performed in rats to demonstrate safety of intranasal CONPs. Further, open field test, pole test, biochemical estimations and brain histopathology was performed to evaluate efficacy of intranasal CONPs in haloperidol-induced PD rat model. Results: The FRAP assay revealed highest antioxidant activity of prepared CONPs at a concentration of 25μg/mL. Confocal microscopy showed deep and homogenous distribution of CONPs in the goat nasal mucus layers. No signs of irritation or injury were seen in goat nasal membrane when treated with optimized CONPs. Scintigraphy studies in rats showed targeted brain delivery of intranasal CONPs and acute toxicity study demonstrated safety. The results of open field and pole test showed highly significant (p < 0.001) improvement in locomotor activity of rats treated with intranasal CONPs compared to untreated rats. Further, brain histopathology of treatment group rats showed reduced neurodegeneration with presence of more live cells. The amount of thiobarbituric acid reactive substances (TBARS) was reduced significantly, whereas the levels of catalase (CAT), superoxide dismutase (SOD), and GSH were increased significantly, while amounts of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) showed significant reduction after intranasal administration of CONPs. Also, the intranasal CONPs, significantly high (p < 0.001) dopamine concentration (13.93 ± 0.85ng/mg protein) as compared to haloperidol-induced control rats (5.76 ± 0.70ng/mg protein). Conclusion: The overall results concluded that the intranasal CONPs could be safe and effective therapeutics for the management of PD.

Propofol protects rats against intra-cerebroventricular streptozotocin-induced cognitive dysfunction and neuronal damage.

Cognitive dysfunction is a severe issue of Alzheimer's disease. Thus, the present study was conducted to enumerate the protective effect of propofol (PPL) in rats against intra-cerebroventricular streptozotocin (STZ)-induced cognitive dysfunction and neuronal damage. The effect of PPL was investigated to evaluate behavioural changes in STZ-induced cognitive dysfunction in Wistar rats using Object Recognition Task (ORT) for nonspatial, Morris Water Maze (MWM) for spatial and locomotor activity. The effect of PPL was also investigated on acetylcholine (ACh) esterase (AChE) activity and oxidative stress markers, e.g., nitrite, malonaldehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH). The level of pro-inflammatory cytokines, e.g., tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, was also studied in the PPL-treated group. The effect of PPL on the level of neurotransmitters, e.g., dopamine (DA), serotonin (5-HT), and norepinephrine (NE) and their metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) levels were also estimated in frozen hippocampal tissues by high-performance liquid chromatography. Histopathology analysis of neurons in the hippocampus of rats was performed using haematoxylin and eosin (H&E) staining. Propofol showed significant improvement in the spatial and nonspatial memory deficit of rats in the MWM test and ORT in rats. It also causes improvement in locomotor activity of rats by preserving ACh via inhibition of AChE. It also potentiates the expression of DA, 5-HT, and NE with a simultaneous reduction in the level of metabolites (DOPAC, HVA, and 5-HIAA). PPL showed a reduction of oxidative stress in rats by restoring the level of nitrite, SOD, MDA, and GSH near to normal. In the PPL-treated group, the level of TNF-α, IL-1β, and IL-6 was found reduced in a dose-dependent manner. In histopathology analysis of neurons in the hippocampus of the STZ rats, PPL causes dose-dependent reduction of pyknosis in the nucleus, which confirmed the protective effect of PPL. The present study demonstrated that PPL could significantly attenuate cognitive dysfunction and neuronal damage in STZ-induced rats.

Сhanges of trace elements in the cerebellum and their influence on the rats behavior in elevated plus maze in the acute period of mild blast-induced brain injury

BackgroundIn connection with the widespread use of explosive devices in military conflicts, in particular in Ukraine, is relevant to detect the biometals changes in the cerebellum and determine the presence of their influence on the behavior changes of rats in the elevated plus maze in the acute period of a mild blast-traumatic brain injury (bTBI). MethodsThe selected rats were randomly divided into 3 groups: Group I - Experimental with bTBI (with an excess pressure of 26–36 kPa), Group II - Sham and Group III - Intact. Behavior studies was in the elevated plus maze. Brain spectral analysis was with using of energy dispersive X-ray fluorescence analysis, after obtaining the quantitative mass fractions of biometals, the ratios of Cu/Fe, Cu/Zn, Zn/Fe were calculated and the data between the three groups were compared. ResultsThe results showed an increase in mobility in the experimental rats, which indicates functional disorders of the cerebellum in the form of maladaptation in space. Changes in cognitive activity also is an evidence of cerebellum suppression, which is indicated by changes in vertical locomotor activity. Grooming time was shortened. We established a significant increase in Cu/Fe and Zn/Fe ratios in the cerebellum, a decrease in Cu/Zn. ConclusionsChanges in the Cu/Fe, Cu/Zn, and Zn/Fe ratios in the cerebellum correlate with impaired locomotor and cognitive activity in rats in the acute posttraumatic period. Accumulation of Fe on the 1st and 3rd day leads to disturbance of the Cu and Zn balance on the 7th day and starts a "vicious cycle" of neuronal damage. Cu/Fe, Cu/Zn, and Zn/Fe imbalances are secondary factors in the pathogenesis of brain damage as a result of primary bTBI.

Effect of Etifoxine on Locomotor Activity and Passive Learning in Rats with Diazepam-Induced Cognitive Deficit

Etifoxine is an anxiolytic drug with a dual mechanism of action. In contrast to conventional benzodiazepine anxiolytics, which induce cognitive dysfunction and myorelaxation, no memory impairment nor a decrease in motor activity is observed with etifoxine. This study aims to evaluate the effects of etifoxine on locomotor activity and passive learning in rats with diazepam-induced memory deficit. Male Wistar rats were treated intraperitoneally for 7 days with: (1) saline; (2) diazepam 2.5 mg/kg bw or (3) diazepam 2.5 mg/kg bw and etifoxine in a dose of 50 mg/kg bw. Activity cage test was used for evaluation of locomotor activity, and step-through and step-down tests were performed to study the passive learning. Etifoxine increased the number of horizontal movements on the 7th and 14th days of the experiment. The drug exhibits anti-amnesic effect in a model of diazepam-induced anterograde amnesia by enhancing long-term memory in passive learning tests. The data obtained suggest that etifoxine can reduce the benzodiazepine-induced cognitive deficit. Moreover, such a combination can alleviate the negative influence of benzodiazepines on locomotor activity. However, additional studies are necessary to translate these results into clinical practice.