Locomotor Activity In Rats Research Articles

TH15. CHRONOTYPE AND NEUROPSYCHIATRIC DISORDERS: A MENDELIAN RANDOMISATION STUDY

Heart failure (HF) is characterized by a blood supply which is insufficient to meet the body's demand. HF can potentially affect the brain and is associated with a high prevalence of depression. However, the mechanisms by which the two are related remain largely unclear. Structural abnormalities of the ventral hippocampus have been observed in depression but have never been reported in HF. In this study, we thus investigated structural brain abnormality in HF using voxel-based morphometry (VBM) and histological analysis in a rat model of HF. T2-weighted images were obtained in rats with HF (n = 20) and sham rats (n = 17) and VBM was used to produce gray matter concentration (GMC) maps. Twenty-four hour locomotor activity was used as a sign of depressive behavior. Brains of HF and sham rats (n = 8, each) were fixed and histologically analyzed for the measurement of neurogenesis, the number of astrocytes and neurite outgrowth in the ventral hippocampus. VBM demonstrated significant GMC decrease in the hippocampus, which was restricted to the ventral segment. Similarly, neurogenesis and neurite outgrowth were significantly decreased and the number of astrocytes was significantly increased in HF rats as compared with sham rats in the ventral hippocampus. GMC values in the ventral hippocampus were significantly and negatively correlated with 24 hour locomotor activity in HF rats. In conclusion, the present study has demonstrated for the first time that the structural abnormality of the ventral hippocampus is associated with depressive symptoms in HF rats.

Effects of fentanyl on acute locomotor activity, behavioral sensitization, and contextual reward in female and male rats

BackgroundAlthough fentanyl has gained widespread prominence, there remains a lack of knowledge on this opioid synthetic agonist, particularly related to sex effects. Therefore, we conducted behavioral tests in female and male rats to measure drug abuse-related responses to fentanyl hypothesizing sex-specific responses. MethodsUsing female and male rats, we measured the effects of acute or repeated administration of fentanyl (20 μg/kg) on locomotor activity (LMA) and behavioral sensitization in an open field test. We further measured contextual-reward and associated locomotor activity during training in a conditioned place preference (CPP) paradigm using a low (4 μg/kg) or high (16 μg/kg) dose of fentanyl. Vaginal lavage samples were collected from female rats in the CPP study, and the estrous phase was determined based on the cytological characterization. ResultsFemale, but not male, rats showed elevated LMA in response to acute fentanyl and behavioral sensitization to repeated administration of fentanyl. Fentanyl produced significant CPP in both sexes, but it was more potent in males. Finally, our secondary investigation of the estrous cycle on fentanyl-CPP suggests that non-estrus phases, likely reflecting high estradiol, may predict the degree of fentanyl preference in females. ConclusionsFentanyl was more potent and/or effective to produce LMA and LMA sensitization in females but more potent to produce CPP in males. Furthermore, the role of sex in fentanyl responses varied across endpoints, and sex differences in LMA were not predictive of sex differences in CPP.

Piceatannol ameliorates behavioural, biochemical and histological aspects in cisplatin-induced peripheral neuropathy in rats.

Peripheral neurotoxicity is a dose-limiting and a potentially lifelong persistent toxicity of cisplatin. This study investigated the possible protective effect of piceatannol (PIC) in a model of cisplatin-induced peripheral neuropathy in rats. PIC (10 mg/kg, i.p.) was given for 7 days, starting 2 days before cisplatin single injection (7 mg/kg, i.p.). Behavioural, biochemical and histological examinations were conducted. Cisplatin administration resulted in thermal hypoalgesia evidenced by increased paw and tail withdrawal latency times in the hotplate and tail flick tests, respectively, and reduced the abdominal constrictions in response to the acetic acid injection. Moreover, cisplatin treatment decreased rat locomotor activity and grip strength. These behavioural alterations were reversed by PIC coadministration. In addition, PIC decreased cisplatin-induced elevation in serum neurotensin and platinum accumulation in sciatic nerve. Also, PIC reversed, to a large extent, cisplatin-induced microscopical alterations in nerve axons and restored normal myelin thickness. Therefore, PIC may protect against cisplatin-induced peripheral neuropathy.

Gabapentin Reduces Alcohol Intake in Rats by Regulating NF-κB Signaling Pathway Via PPAR γ.

Increasing preclinical and clinical reports have demonstrated the efficacy of gabapentin (GBP) in treating alcohol use disorder (AUD). However, the mechanism of the effects of GBP in AUD is largely unknown. Herein, we sought to investigate the effect of GBP in a rat model of AUD and explore the underlying mechanism. The intermittent access to 20% ethanol in a 2-bottle choice (IA2BC) procedure was exploited to induce high voluntary ethanol consumption in rats. The rats were treated daily for 20days with different doses of GBP, simultaneously recording ethanol/water intake. The locomotor activity and grooming behavior of rats were also tested to evaluate the potential effects of GBP on confounding motor in rats. The levels of IL-1β and TNF-α in serum and hippocampus homogenate from the rats were detected by using ELISA. The expressions of peroxisome proliferator-activated-receptor γ (PPAR-γ) and nuclear factor-κB (NF-κB) in the hippocampus were determined by immunofluorescence and western blot. GBP reduced alcohol consumption, whereas increased water consumption and locomotor activity of rats. GBP was also able to decrease the levels of IL-1β and TNF-α in both serum and hippocampus, in addition to the expression of NF-κB in the hippocampus. Furthermore, these effects attributed to GBP were observed to disappear in the presence of bisphenol A diglycidyl ether (BADGE), a specific inhibitor of PPAR-γ. Our findings revealed that GBP could activate PPAR-γ to suppress the NF-κB signaling pathway, contributing to the decrease of ethanol consumption and ethanol-induced neuroimmune responses.

Impact of cisplatin administration on cerebellar cortical structure and locomotor activity of infantile and juvenile albino rats: the role of oxidative stress.

The central neurotoxicity of cisplatin (CisPt) has always raised questions especially during development, but few studies are available. Hence, this work was designed to assess the CisPt's impacts on the postnatal rat cerebellum via evaluation of locomotor activity, histological and immunohistochemical studies, and to focus on cerebellar oxidative stress-related alterations. Eighty newborn pups were divided into 2 equal experimental groups: the control group was kept without any treatment and CisPt-treated group received a single subcutaneous injection of CisPt (5μg /g b.w.) in their nape at PD10. Ten rats at PD11, PD17, and PD30 ages were weighed, then deeply anesthetized and sacrificed. For locomotor assessment, 20 pups were divided equally into control and CisPt-treated groups and tested at PD11-13, PD15-17, and PD28-30 ages. CisPt-treated rats suffered from decreased motor activity and showed decreased body and cerebellar weights, reduced levels of enzymatic antioxidants (SOD and CAT), and non-enzymatic antioxidant defense (GSH), and increase of lipid peroxidation marker (MDA). Histopathologically, CisPt sowed deleterious changes within cerebellar cortical layers in the form of vacuolations, decreased thickness, and hemorrhage (in PD17), while Purkinje cells exhibited profound degenerative changes in the form of swelling, disrupted arrangement, distortion, and nuclear shrinkage. In CisPt-treated rats, GFAP demonstrated upregulated, hypertrophied, and branched Bergmann glial fibers and reactive astrogliosis. Immuno-localization of Ki-67-positive cells revealed defective migration associated with decreased proliferation in early ages in addition to glial proliferation in PD30. In conclusion, CisPt causes oxidative stress-related deleterious effects on structure of developing cerebellar cortex and affects locomotor activity.

Oxygen Enrichment Mitigates High-Altitude Hypoxia-Induced Hippocampal Neurodegeneration and Memory Dysfunction Associated with Attenuated Tau Phosphorylation.

Cai, Jing, Junyong Ruan, Xi Shao, Yuanjun Ding, Kangning Xie, Chi Tang, Zedong Yan, Erping Luo, and Da Jing. Oxygen enrichment mitigates high-altitude hypoxia-induced hippocampal neurodegeneration and memory dysfunction associated with attenuated tau phosphorylation. High Alt Med Biol. 22:274-284, 2021. Background: Brain is predominantly vulnerable to high-altitude hypoxia (HAH), resulting in neurodegeneration and cognitive impairment. The technology of oxygen enrichment has proven effective to decrease the heart rate and improve the arterial oxygen saturation by reducing the equivalent altitude. However, the efficacy of oxygen enrichment on HAH-induced cognitive impairments remains controversial based on the results of neuropsychological tests, and its role in HAH-induced hippocampal morphological and molecular changes remains unknown. Therefore, this study aims to systematically investigate the effects of oxygen enrichment on the memory dysfunction and hippocampal neurodegeneration caused by HAH. Materials and Methods: Fifty-one male Sprague-Dawley rats were equally assigned to three groups: normal control, HAH, and HAH with oxygen enrichment (HAHO). Rats in the HAH and HAHO groups were exposed to hypoxia for 3 days in a hypobaric hypoxia chamber at a simulated altitude of 6,000 m. Rats in the HAHO group were supplemented with oxygen-enriched air, with 12 hours/day in the hypobaric hypoxia chamber. Results: Our results showed that oxygen enrichment improved the locomotor activity of HAH-exposed rats. The Morris water maze test revealed that oxygen enrichment significantly ameliorated HAH-induced spatial memory deficits. Oxygen enrichment also improved morphological alterations of pyramidal cells and the ultrastructure of neurons in the hippocampal CA1 region in rats exposed to acute HAH. Tau hyperphosphorylation at Ser396, Ser262, Thr231, and Thr181 was also significantly attenuated by oxygen enrichment in HAH-exposed rats. Conclusions: Together, our study reveals that oxygen enrichment can ameliorate HAH-induced cognitive impairments associated with improved hippocampal morphology and molecular expression, and highlights that oxygen enrichment may become a promising alternative treatment against neurodegeneration for humans ascending to the plateau.

Effects of subanesthetic intravenous ketamine infusion on neuroplasticity-related proteins in male and female Sprague-Dawley rats.

Although ketamine, a multimodal dissociative anesthetic, is frequently used for analgesia and treatment-resistant major depression, molecular mechanisms of ketamine remain unclear. Specifically, differences in the effects of ketamine on neuroplasticity-related proteins in the brains of males and females need further investigation. In the current study, adult male and female Sprague-Dawley rats with an indwelling jugular venous catheter received an intravenous ketamine infusion (0, 10, or 40 mg/kg, 2-h), starting with a 2 mg/kg bolus for ketamine groups. Spontaneous locomotor activity was monitored by infrared photobeams during the infusion. Two hours after the infusion, brain tissue was dissected to obtain the medial prefrontal cortex (mPFC), hippocampus including the CA1, CA3, and dentate gyrus, and amygdala followed by Western blot analyses of a transcription factor (c-Fos), brain-derived neurotrophic factor (BDNF), and phosphorylated extracellular signal-regulated kinase (pERK). The 10 mg/kg ketamine infusion suppressed locomotor activity in male and female rats while the 40 mg/kg infusion stimulated activity only in female rats. In the mPFC, 10 mg/kg ketamine reduced pERK levels in male rats while 40 mg/kg ketamine increased c-Fos levels in male and female rats. Female rats in proestrus/estrus phases showed greater ketamine-induced c-Fos elevation as compared to those in diestrus phase. In the amygdala, 10 and 40 mg/kg ketamine increased c-Fos levels in female, but not male, rats. In the hippocampus, 10 mg/kg ketamine reduced BDNF levels in male, but not female, rats. Taken together, the current data suggest that subanesthetic doses of intravenous ketamine infusions produce differences in neuroplasticity-related proteins in the brains of male and female rats.

Antiparkinsonian Activity of Aqueous Extract of Agaricus Blazei Murill in Rotenone-induced Parkinson’s Disease

Background: Parkinsons disease is a chronic neurological disorder which may be due to reduction in the dopaminergic neurons in the brain. However, Agaricus blazei is a rich source of natural antioxidants.
 Aim: In this study, antiparkinsonian activity of Agaricus blazei Murill was evaluated using different animal models.
 Method: Antiparkinsonian activity was evaluated using two different doses (273 mg/kg and 819 mg/kg) of Agaricus blazei Murill. Rotenone and sunflower oil were used as positive and negative control, respectively. Catalepsy test, rotarod test, exploratory behavior test (rearing) and locomotor activity test were conducted to observe antiparkinsonian activity of the drug in rats.
 Result: The results of the animal models were confirmed by determining the levels of reduced glutathione, total protein, thiobarbituric acid reactive substances (TBARS) and nitric oxide in the animal brain. Pretreatment with Agaricus blazei Murill, showed marked reduction in rotenone-induced catalepsy and a significant increase in exploratory behavior, muscular activity, and locomotor activity in rats. Agaricus blazei Murill has also shown extremely significant effect in decreasing the oxidative stress in the animal brain by increasing the brain levels of reduced GSH and total proteins and decreasing the levels of nitrite and TBARS.
 Conclusion: The results of rotenone-induced catalepsy, exploratory behavior, rotarod test and locomotor activity showed that Agaricus blazei Murill exerts a significant ameliorative effect on Parkinson’s disease in rats.

Acupuncture stimulation at HT7 as a non-pharmacological therapy for sleep disorder caused by caffeine administration in rats.

Insomnia is one of the most common sleep disorders and is difficult to completely treat because of the undesirable side effects of hypnotics. The present study was designed to investigate the hypnotic effect of acupuncture stimulation at HT7 on caffeine-induced sleep disorders and locomotor activity in rats. We also evaluated neuronal activity changes in the arousal region of the basal forebrain. Rats received intraperitoneal injections of caffeine, and then electroencephalogram power spectrum analysis and locomotor activity measurements were performed. Stimulation at HT7 was performed using a mechanical acupuncture instrument (MAI) before caffeine injection, and its effects on caffeine-induced changes in sleep architecture, locomotor activity and c-Fos expression were examined. Caffeine injection (7.5 mg/kg) produced a significant decrease in slow-wave sleep and an increase in wake time compared with saline injection. Caffeine injection also increased locomotor activity and c-Fos expression in the medial septum-vertical limb of the diagonal band of Broca (MS-VDB), one of the arousal regions of the basal forebrain. Stimulation at HT7 with the MAI alleviated the caffeine-induced sleep disturbance and the increase in locomotor activity. In addition, MAI treatment at HT7, compared with treatment at a location not corresponding to any traditional acupuncture point, reduced the caffeine-induced increase in c-Fos expression. These results indicate that the hypnotic effect of HT7 acupuncture stimulation on caffeine-induced insomnia was associated with suppression of neuronal activity in the basal forebrain.

Tetrahydropalmatine reduces cell death and improves functional recovery after traumatic spinal cord injury in ratsTetrahydropalmatine reduces cell death and improves functional recovery after traumatic spinal cord injury in rats

Purpose: To investigate the effectiveness of tetrahydropalmatine (THP) in the treatment of spinal cord injury (SCI) in rats.
 Methods: Adult Sprague Dawley rats were divided into 3 groups: normal control group, SCI group, and SCI group treated with THP (100 mg kg-1). The effect of THP on spinal cord water content, levels of inflammatory mediators, oxidative stress and apoptosis were determined. Locomotor activity in rats was measured using Basso, Beattie and Bresnahan (BBB) scores. Various oxidative stress markers as well as cytokine levels (NF-ĸB, IL-6, IL-1β and TNF-α were determined. Apoptotic index was measured using TUNEL assay.
 Results: After 72 h of treatment with THP, BBB scores in SCI group of rats significantly increased from 4.19 ± 0.41 to 8.89 ± 0.47 (p < 0.05). Tunel assay revealed a higher apoptotic index (42.50 ± 3.19) in the tissues of SCI rats than in SCI rats treated with THP (31.48 ± 1.19, p < 0.01). Expressions of inflammatory cytokines were significantly upregulated in SCI rats. However, THP administration resulted in significant downregulation of the expressions (p < 0.01).
 Conclusion: These results indicate that THP attenuates traumatic SCI in rats via modulation of the levels of anti-inflammatory mediators. Thus, THP has a promising potential for the management of SCI.

Longevity, tumor, and physical vitality in rats consuming ginsenoside Rg1

BackgroundEffects of the major ginsenoside Rg1 on mammalian longevity and physical vitality are rarely reported. PurposeTo examine longevity, tumor, and spontaneous locomotor activity in rats consuming Rg1. MethodsA total of 138 Wistar rats were randomized into 2 groups: control (N = 69) and Rg1 (N = 69). Rg1 (0.1 mg/kg per day) were orally supplemented from 6 months of age until natural death. Spontaneous mobility was measured by video-tracking together with body composition (dual energy x-ray absorptiometry) and inflammation markers at 5, 14, 21, and 28 months of age. ResultsNo significant differences in longevity (control: 706 days; Rg1: 651 days, p = 0.77) and tumor incidence (control: 19%; Rg1: 12%, p = 0.24) were observed between the two groups. Movement distance in the control group declined significantly by ∼60% at 21 months of age, together with decreased TNF-α (p = 0.01) and increased IL-10 (p = 0.02). However, the movement distance in the Rg1 group was maintained ∼50% above the control groups (p = 0.01) at 21 months of age with greater magnitudes of TNF-α decreases and IL-10 increases. Glucose, insulin, and body composition (bone, muscle and fat percentages) were similar for both groups during the entire observation period. ConclusionThe results of the study suggest a delay age-dependent decline in physical vitality during late life by lifelong Rg1 consumption. This improvement is associated with inflammatory modulation. Significant effects of Rg1 on longevity and tumorigenesis were not observed.

Putative Anti-Immobility Action of Acute Insulin Is Attributable to an Increase in Locomotor Activity in Healthy Wistar Rats

Background/Aims: Anti-immobility actions of insulin in diabetic rats that are subjected to the forced swim test (FST) have been reported. In this test, low doses of antidepressants exert actions after long-term treatment, without affecting locomotor activity in healthy rats. Few studies have compared acute and chronic actions of insulin with antidepressants in healthy rats. Methods: We hypothesized that if insulin exerts a true anti-immobility action, then its effects must be comparable to fluoxetine in both a 1-day treatment regimen and a 21-day treatment regimen in healthy, gonadally intact female Wistar rats. Results: The results showed that low levels of glycemia were produced by all treatments, including fluoxetine, and glycemia was lower in proestrus-estrus than in diestrus-metestrus. None of the treatments or regimens produced actions on indicators of anxiety in the elevated plus maze. Insulin in the 1-day regimen increased the number of crossings and rearings in the open field test and caused a low cumulative immobility time in the FST. These actions disappeared in the 21-day regimen. Compared with the other treatments, fluoxetine treatment alone or combined with insulin produced a longer latency to the first period of immobility and a shorter immobility time in the chronic regimen in the FST, without affecting locomotor activity, and more pronounced actions were observed in proestrus-estrus (i.e., a true anti-immobility effect). Conclusion: These results indicate that insulin does not produce a true antidepressant action in healthy rats. The purported antidepressant effects that were observed were instead attributable to an increase in locomotor activity only in the 1-day regimen.

THE EFFECTS OF SYSTOLIC ARTERIAL PRESSURE ON LOCOMOTOR ACTIVITY IN CONGENIC RATS DERIVED FROM STROKE PRONE SPONTANEOUSLY HYPERTENSIVE RATS AND WISTAR KYOTO RATS

Objective: The systolic arterial pressure (SAP) levels of congenic rats were reported to be intermediate between those of stroke-prone spontaneously hypertensive (SHRSP) rats and Wistar Kyoto (WKY) rats, and the congenic rats were reported to exhibit higher locomotor activity than SHRSP and WKY rats. Locomotor activity in the early morning was higher in the congenic rats than in the other two strains. However, no study on the relationship between SAP and locomotor activity in congenic rats has been performed. Therefore, we aimed to examine this topic. Design and method: We used 10 mature male congenic rats and age- and gender-matched SHRSP and WKY rats (n = 10 each) as the controls. We measured the SAP and locomotor activity of the rats telemetrically. We estimated best-fit curves of locomotor activity using the maximal entropy method. Results: The congenic rats exhibited the highest locomotor activity counts (congenic rats vs. SHRSP rats vs. WKY rats: 58 (23, 89) vs. 18 (4, 40) vs. 4 (1, 8) counts/10 seconds (median, Q1, Q3), P = 0.0010). The congenic rats also exhibited SAP levels that were intermediate between those of the SHRSP and WKY rats (congenic rats vs. SHRSP rats vs. WKY rats: 194 ± 7 vs. 229 ± 7 vs. 117 ± 4 mmHg (mean ± SD, P = 0.0098). The strongest correlation between locomotor activity and SAP was seen in the congenic rats (Y = -1851.3 + 9.87X, rS = 0.592, P = 0.00001). The ratio of the increase in locomotor activity to the increase in SAP was highest in the congenic rats (congenic rats vs. SHRSP rats vs. WKY rats: 7.05 (4.92, 10.20) vs. 0.04 (0.87, 0.88) vs. 0.11 (3.46, 3.55)(median, Q1, Q3); SHRSP rats vs. congenic rats: P < 0.01; SHRSP rats vs. WKY rats: n.s.; congenic rats vs. WKY rats: P < 0.05). Conclusions: Among these three rat strains, the response of locomotor activity to increases in SAP was strongest in the congenic rats.

CXCR4 inhibition with AMD3100 attenuates amphetamine induced locomotor activity in adolescent Long Evans male rats.

Adolescent psychostimulant abuse has been on the rise over the past decade. This trend has demonstrable ramifications on adolescent behavior and brain morphology, increasing risk for development of addiction during adolescence and in later adulthood. Neuroimmune substrates are implicated in the etiology of substance use disorders. To add to this body of work, the current study was developed to explore the role of a chemokine receptor, CXC Chemokine Receptor 4 (CXCR4), in the development of amphetamine (AMPH) sensitization. We targeted CXCR4 as it is implicated in developmental processes, dopaminergic transmission, neuroimmune responses, and the potentiation of psychostimulant abuse pathology. To evaluate the role of CXCR4 activity on the development of AMPH sensitization, a CXCR4 antagonist (Plerixafor; AMD3100) was administered to rats as a pretreatment variable. Specifically, adolescent Long Evans male rats (N = 37) were divided into four groups: (1) AMD3100 (IP, 4.0 mg/kg) + AMPH (IP, 4.0 mg/kg), (2) saline (SAL; 0.9% NaCl) + AMPH, (3) AMD3100 + SAL, and (4) SAL + SAL. Animals were first habituated to locomotor activity (LMA) chambers, then injected with a pretreatment drug (AMD3100 or SAL) followed by AMPH or SAL every other for four days. After a one-week withdrawal period, all animals were administered a low challenge dose of AMPH (IP, 1.0 mg/kg). AMPH-injected rats displayed significantly more locomotor activity compared to controls across all testing days. CXCR4 antagonism significantly attenuated AMPH-induced locomotor activity. On challenge day, AMD3100 pre-treated animals exhibited diminutive AMPH-induced locomotor activity compared to SAL pre-treated animals. Postmortem analyses of brain tissue revealed elevated CXCR4 protein levels in the striatum of all experimental groups. Our results implicate CXCR4 signaling in the development of AMPH sensitization and may represent an important therapeutic target for future research in psychostimulant abuse.

Mash-1 modified neural stem cells transplantation promotes neural stem cells differentiation into neurons to further improve locomotor functional recovery in spinal cord injury rats.

Spinal cord injury (SCI) leads to severe motor and sensory dysfunctions. Neural stem cells (NSCs) transplantation therapy plays a positive role in functional recovery after SCI, but the effectiveness of this therapy is limited by inadequate differentiation ability of transplanted NSCs. Mammalian achaete-scute homologue-1 (Mash-1) has been reported to improve differentiation of NSCs. Thus, this study modified NSCs with Mash-1 to repair SCI. NSCs isolated from rat embryo hippocampus were cultured and identified in vitro and further transfected with the lentiviral vectors (Lv-Mash-1). After establishing a SCI rat model, the rats were transplanted with Mash-1 modified NSCs, the histopathological changes of rat spinal cord were detected by hematoxylin-eosin (HE) staining, and the locomotor activity of rats was evaluated with the Basso, Beattie and Bresnahan (BBB) scale. The NSCs cultured in vitro or extracted from SCI rat spinal cord were identified by immunofluorescence (IF). Mash-1, β3-Tubulin, and NeuN expressions in those cells were determined by Western blotting and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). NSCs isolated from rat embryo hippocampus were Nestin- and NeuN-positive. NSC transplantation modified by Mash-1 increased BBB score of SCI rats and promoted recovery in lesion site of SCI rats. Mash-1 overexpression also promoted β3-Tubulin and NeuN expressions in NSCs cultured in vitro or extracted from spinal cord of SCI rats. Mash-1 overexpression promoted NSC differentiation into neurons, and further improved locomotor functional recovery of SCI rats.

A Novel Pharmacological Protective Role for Safranal in an Animal Model of Huntington's Disease.

Huntington's disease (HD) is a progressive, neurodegenerative and inherited disease and recent years have witnessed the understanding of the cellular and molecular mechanisms related to HD. Safranal, an organic compound isolated from saffron, has been reported to have anti-apoptotic, anti-inflammatory and antioxidant activity and has studied in chronic and neurodegenerative disease. Therefore, this study was aimed to investigate the effect of safranal on 3-NP induced locomotor activity and biochemical alterations in rats. To this aim, 40 male Wistar rats weighting 250-300g were divided into 5 groups (n = 8) including sham, 3-NP group (10mg/kg) as control and treatment groups (3-NP + safranal 0.75, 1.5 and 3mg/kg) in two weeks duration of treatment. Behavioral/movement assessments in addition to oxidant/antioxidant markers in rat cortex and striatum were evaluated in control and treatment groups. Here, we found that safranal significantly alleviated 3-NP-induced changes of body weight, rotarod activity, number of vacuous chewing movements (VCMs), and locomotor activity. In addition, brain tissue assessments in cortex and striatum revealed that safranal could prevent the elevation of nitrite and malondialdehyde (MDA) levels as well as decrease of superoxide dismutase (SOD), catalase activity and glutathione (GSH) induced by 3-NP. In conclusion our results showed that safranal prevented the motor dysfunction induced by 3-NP in animal model of Huntington's disease. This effect might be due to its modulating effect on oxidants-antioxidant balance.

A Novel Nutraceutical Formulation Can Improve Motor Activity and Decrease the Stress Level in a Murine Model of Middle-Age Animals.

Ageing is a genetically programmed physiological process that is modulated by numerous environmental factors, associated with decreasing physiological function, decreasing reproductive rate and increasing age-related mortality rate. Maintaining mobility performance and physical function in the elderly is the main objective of the successful ageing concept. In this study, we aimed to evaluate the beneficial effect of a novel nutraceutical formulation containing Centella asiatica L. extract, vitamin C, zinc and vitamin D3 (as cholecalciferol) on motor activity and anxiety with the use of a murine model of old animals, as a means of providing proof for clinical use in the elderly, for enhancing physical strength and improving life quality. Eighteen Sprague Dawley 18 months old male rats were divided into three groups and received corn oil (the control group) or 1 capsule/kg bw Reverse supplement (treatment group 1) or 2 capsules/kg bw Reverse supplement (treatment group 2), for a period of 3 months. The Reverse supplement (Natural Doctor S.A, Athens, Greece) contains 9 mg Centella asiatica L. extract, vitamin C (200 mg as magnesium ascorbate), zinc (5 mg as zinc citrate), vitamin D3 (50 µg as cholecalciferol) per capsule. Before and after the treatment, the motor function and behavioral changes for anxiety and depression were evaluated using the open-field test, elevated plus-maze test and rotarod test. The supplementation with Reverse (Natural Doctor S.A) supplement can improve the locomotor activity in old rats in a dose-dependent manner, as demonstrated by an increase in the latency to leave from the middle square, in the number of rearings in the open field test, in the time spent in the open arms and time spent in the center in the elevated plus-maze test and the latency to all in all three consecutive trials in the rotarod test. Stress also decreased significantly in a dose-dependent manner, following the treatment with Reverse supplement, as was demonstrated by the decrease in the number of groomings at the open field test and time spent in the dark and the number of groomings at the elevated plus-maze test.

Evaluation of Nootropic Activity of Limonia acidissima Against Scopolamine-induced Amnesia in Rats.

The present study aimed to evaluate the nootropic activity of Limonia acidissima in rats. Methanolic extract of Limonia acidissima was used to evaluate nootropic activity, piracetam (200 mg/kg, i.p.) was used as a standard, and scopolamine (1 mg/kg, i.p.) was used to induce amnesia. The effect of drugs on learning and memory in rats was evaluated by using the Y-maze task and elevated plus maze on scopolamine-induced amnesia models. Locomotor activity was performed using an actophotometer. Also, levels of acetylcholinestrease, including histopathological examination of rat brains, were assessed. Methanolic extract of Limonia acidissima showed increased alteration of the behavior response and percentage spontaneous alteration with the Y-maze task. In the elevated plus maze scopolamine-induced amnesia model, methanolic extract of Limonia acidissima showed a decrease in transfer latency, which is indicative of cognition improvement. Methanolic extract increased locomotor activity in rats and decreased the levels of acetylcholinestrease enzyme significantly. A histopathological study with both low and high doses of extract showed effective regenerative scores as compared to normal control, negative control and standard treatment. The results suggested that the administration of methanolic extract of Limonia acidissima enhances learning and memory in different experimental models. The histopathological study revealed the neuroprotective property of the extract. The study indicates that the extract may be used in the treatment of Alzheimer's disease.

Where do we cut the bell-shaped curve of CIAS?

While the long-term administration of antipsychotics is known to cause dopamine supersensitivity psychosis (DSP), recent studies revealed that DSP helps form the foundation of treatment resistance. Electroconvulsive shock (ES) is one of the more effective treatments for treatment-resistant schizophrenia. The objective of this study was to examine whether repeated ES can release rats from dopamine supersensitivity states such as striatal dopamine D2 receptor (DRD2) up-regulation and voluntary hyperlocomotion following chronic administration of haloperidol (HAL). HAL (0.75 mg/kg/day) was administered for 14 days via mini-pumps implanted in rats, and DRD2 density and voluntary locomotion were measured one day after drug cessation to confirm the development of dopamine supersensitivity. The rats with or without dopamine supersensitivity received repeated ES or sham treatments, and then DRD2 density was assessed and a voluntary locomotion test was performed. Chronic treatment with HAL led to the up-regulation of striatal DRD2 and hyperlocomotion in the rats one day after drug cessation. We thus confirmed that these rats experienced a dopamine supersensitivity state. Moreover, after repeated ES, locomotor activity and DRD2 density in the DSP model rats fell to the control level, while an ES sham operation had no effect on the dopamine supersensitivity state. The present study suggests that repeated ES could release DSP model rats from dopamine supersensitivity states. ES may be helpful for patients with DSP.

16-Substituted steroids alleviate LPS-induced neurodegenerative disorders in rats

The neuroprotective effects of some 16-substituted steroidal derivatives against the locomotive impairment and cognitive deficits in the lipopolysaccharide (LPS)-induced neuroinflammation model of rats have been investigated. The in vivo and in vitro evaluations include behavioural tests (actophotometer, block tests, Morris water maize and elevated plus maize), estimation of the biochemical parameters such as acetylcholinesterase, lipid peroxide, reactive oxygen, and nitric oxide species and molecular assays for the key proinflammatory mediators like Tumour Necrosis Factor alpha (TNF-α) and Interleukin 1 beta (IL- 1β) after 21 days of the treatment with the steroids. Behavioural and biochemical studies indicated impairment in the locomotor activity and cognitive dysfunction in rats after LPS treatment. In addition, higher levels of TNF-α and IL-1β in the blood serum of the rats were also noticed. However, significant alleviation of LPS-induced movement and memory disorders was observed in LPS-injected rats after treatment with 16-substituted steroidal derivatives 1–11. Furthermore the biochemical and molecular studies revealed suppression of oxidative and nitrosative stress, decreased acetylcholinesterase activity, and reduction of TNF-α and IL-1β levels after treatment with compounds 1–11. Among all the 16-substituted steroidal derivatives, the compounds 8 and 11 were found to be the most active neuroprotective agents and produced effects marginally better than standard drug dexamethasone.