Number Of Grooming Research Articles

Neuroprotective Activity of Polyherbal Formulation on Colchicine Induced Alzheimer’s Disease in Rat Model

Objective: The current study was designed to study the neuroprotective effect of Polyherbal formulation against the Colchicine-induced Alzheimer’s disease rat model. Methods: The memory enhancing activity of Polyherbal formulation was demonstrated by the intracerebroventricular administration of colchicine in Sprague-dawley rats. The effect of Polyherbal formulation were studied by evaluating the neurobehavioral assessment parameters like Morris water maze test, Locomotor activity, Open filed and Elevated plus maze test were performed at 0, 7, 14 and 28 days for assessing the cognitive and gross behavioral activities in all groups. Results and Discussion: The effect of Polyherbal formulation shows a neuroprotective activity with significant (p<0.001) decrease in Mean transfer latency, Time spent in open arm, Number of entries in open arm, escape latency, number of ambulatory movement, latency, numbering of rearing, number of grooming, rest and significant (p<0.001) increase in time spent closed arm, number of entries in closed arm, Probe trail, time spent in platform quadrant and spontaneous locomotion, number of ipsilateral rotation. Conclusion: In conclusion, the result of current study evidenced that the Polyherbal formulation (PHF) showed potent neuroprotective activity against colchicine induced Alzheimer’s disease.

Protective effects of a probiotic-fermented germinated grain complex on neurotransmitters and sleep quality in sleep-deprived mice.

To explore the effects of probiotic fermentation products of germinated grains on cognitive and sleep improvement in mice with sleep deprivation induced by chlorophenylalanine (PCPA), and to provide theoretical and experimental basis for the development of natural products to alleviate insomnia. ELISA and high-performance liquid chromatography (HPLC) were used to determine the contents of γ-aminobutyric acid and L-theanine in fermentation products. Open Field Test was used to analyze the changes of emotional behavior between groups before and after intervention. ELISA was used to analyze the changes of hypothalamic serotonin, GABA, glutamate, and serum interleukin 6. 16S rRNA sequencing was used to analyze the changes of intestinal flora before and after the intervention of compound fermentation products. LC-MS/MS was used to analyze the changes of intestinal SCFAs before and after the intervention. The content of GABA and L-theanine in 7 L fermentation products was 12.555 μmol/L (1.295 mg/L) and 0.471 mg/mL by ELISA. Compared with the PCPA-induced Model group, the sleep duration of the KEY group was statistically significant (p < 0.0001). Compared with the PCPA-induced Model group, the number of crossing the central lattice in the KEY group was significantly increased, and the number of grooming was significantly reduced (all p < 0.05), suggesting that the anxiety behavior of the mice was improved. In addition, this study found that the compound fermentation products could significantly increase the content of neurotransmitters such as 5-HT, GABA and Glu in the hypothalamus of mice, reduce the content of inflammatory factors such as IL-6, IL-1β and TNF-α in serum, regulate the structure of intestinal flora and increase the content of short-chain fatty acids. Probiotic fermentation products of germinated grains can significantly improve sleep deprivation in PCPA mice, which may be related to regulating the levels of neurotransmitters and inflammatory factors, improving the structure of intestinal flora, and increasing the content of short-chain fatty acids. This study provides new candidates and research directions for the development of natural drugs to alleviate insomnia.

Gens PSD-95 and GSK-3β expression improved by hair follicular stem cells-conditioned medium enhances synaptic transmission and cognitive abilities in the rat model of vascular dementia.

Vascular dementia (VaD) is a common type of dementia. The aim of this study was to investigate the cellular and molecular mechanism of conditioned medium (CM) in VaD. The rats were divided into four groups of control (n=9), sham-operation (n=10), VaD with vehicle (n=9), and VaD with CM (n=12) that received CM on days 4, 14, and 24 after 2VO. Before sacrificing the rats, cognitive performance was assessed through the open-field (OP), passive-avoidance, and Morris-water maze. The field-potential recording was used to investigate basal synaptic transmission (BST) and long-term potentiation (LTP). Subsequently, the hippocampus was dissected, and real-time PCR was used to quantify the expression levels of β1-catenin, insulin-like growth factor-1 (IGF-1), transforming growth factor-beta (TGF-β), glycogen synthase kinase-3β (GSK-3β), postsynaptic density protein 95 (PSD-95), and NR2B genes. The results indicated impaired performance in behavioral tests in 2VO rats, coupled with reductions in BST and LTP induction. The expression levels of β1-catenin, IGF-1, PSD-95, and TGF-β genes decreased, whereas NR2B and GSK-3β expression increased. Treatment with CM restores the expression of PSD-95 and GSK-3β as well as fear-memory, spatial learning, and grooming number without a positive effect on memory retrieval, time spent on the periphery and center of OP. The BST recovered upon administration of CM but, the LTP induction was still impaired. The recovery of BST in VaD rats appears to be the most important outcome of this study which is caused by the improvement of gene expression and leads to the restoration of fear memory.

Effects of Phragmanthera capitata (Loranthaceae) on a model of anxiety-like behaviours induced by chronic immobilization stress in mice

This work aims to evaluate the anxiolytic-like effects of Phragmanthera capitata in a model of chronic immobilization stress in mice. Groups of mice were treated in ten consecutive days as follows: a normal control group (NaCl 0.9% per os), a negative control group (chronic immobilization stress + NaCl 0.9% per os), three test groups that were submitted to chronic immobilization stress (CIS) and received three doses of the plant (25, 125, and 250 mg/kg, p.o), and a positive control group (chronic immobilization stress + diazepam 2 mg/kg, i.p). Open field and dark/light tests were used for the evaluation of anxiolytic effects. Antioxidant activities and the involvement of gabaergic neurotransmission were determined by measuring the levels of malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT), gamma amino butyric acid (GABA), and GABA-transaminase (GABA-T) in the brain. Our results show that the highest dose of Phragmanthera capitata induced a significant increase (p &lt; 0.001) of time spent in the centre, number of crossing and number of grooming in the open field test and a significant increase (p &lt; 0.001) of time spent in the light compartment and the latency of the first escape in the light compartment of the dak/light test. The level of MDA and the activity of GABA-T were significantly decreased by the Phragmanthera capitata while reduced GSH, CAT and GABA, levels were increased. These results suggest that Phragmanthera capitata possesses anxiolytic-like effects that may be supported by its antioxidant activities and or the GABA neurotransmission.

Antidepressant and anxiolytic-like activities of the dichloromethane/methanol extract of Crateva adansonii in mice exposed to chronic mild stress

Crateva adansonii (CA) is traditionally used in the treatment of epilepsy and memory loss. This work aims to evaluate the antidepressant and anxiolytic activities of the dichloromethane/methanol extract of CA trunk bark in a chronic unpredictable stress-induced depression (UCMS) model in mice. After exposure of mice to UCMS for 42 days, anhedonia was assessed using the sucrose preference test, antidepressant effects by the forced swim and caudal suspension tests, anxiolytic effects by the light/dark compartment (LDB) and open arena (OF) tests. Oxidative stress parameters Malondialdehyde (MDA), Superoxide Dismutase (SOD), Catalase (CAT), and Reduced Glutathione (GSH) were assessed. The results showed that multiple administrations of C. adansonii extract (150 and 300 mg/kg, resulted in a significant increase from 38.5% to 64.9% (p&lt;0.001) in sucrose intake and a decrease from 47 seconds to 14 seconds in the immobility time in the forced swim test compared to the UCMS group. The extract significantly (p&lt;0.001) reversed the time spent in the dark box at 150 mg/kg, and the number of groomings at 150 and 300 mg/kg compared to the UCMS group in the LDB and OF test. There was also a significant (p&lt;0.001) improvement in SOD, GSH, and a reversal of MDA. The extract of CA improved symptoms of depression and anxiety in mice treated with different dose. The effects observed would be due to the presence in the extract of polyphenols such as flavonoids. These effects would justify the use of this extract in traditional medicine.

Specific Manifestations of Neurotoxicity of Some Drug Combinations for Treatment of Drug Resistant Tuberculosis from the Perspective of Experimental Studies

The objective: to evaluate comparative neurotoxicity of combinations of anti-tuberculosis and antimicrobial drugs with different and similar toxic potentials assessing behavioral changes in rats.Subjects and Methods: non-linear female rats divided in 3 groups were used in this study. For 14 days, the rats received a daily combinations of drugs: Group 1 – Mxf + Lzd + Cs + Pto, Group 2 – Mxf + Bdq + Cs + Z , and Group 3 – Bdq + Lzd + Cfz + Z. Neurotoxicity was assessed by changes in behavioral responses using Open Field Test. The number of crossed squares and racks was recorded which characterized horizontal and vertical activity, also peeping into burrows (exploratory activity), the number of groomings (washing and scratching) and physiological functions were registered.Results. In rats of Group 1 versus baseline parameters, we observed a significant limitation of horizontal motor activity and a sharp decrease (by 5 times) in exploratory activity, a 2.8-fold decrease in the number of groomings which indicated emotional suppression. In rats of Groups 2 and 3, the decrease in motor and exploratory activity was insignificant but there was a more pronounced emotional depression. The use of the Mxf + Lzd + Cs + Pto combination in which all drugs possessed a neurotoxic potential, led to diverse and profound changes in behavioral responses which indicated a pronounced neurotoxic effect.

Gestational arsenic exposure induces anxiety-like behaviors in F1 female mice by dysregulation of neurological and immunological markers.

Arsenic is a harmful heavy metal and a well-known developmental neurotoxicant. Previously, we have reported that gestational arsenic exposure resulted in impaired social behaviors in F1 and F2 male mice. However, little is known about the developmental arsenic exposure on anxiety-like behavior. This study aimed to detect the effect of gestational arsenic exposure on anxiety-like behavior and related gene expressions in 74-week-old F1 female mice. Pregnant C3H/HeN mice (F0) were given drinking water containing 85 ppm sodium arsenite (NaAsO2) from gestational day 8 to 18. The control mice were given tap water only. At 74-week-old, open field test was performed, then anxiety and apoptosis-related factors were determined by real_time RT_PCR and immunohistochemical analyses. The arsenite-exposed F1 female mice showed decreased center entry and center time in open field test. In addition, the number of grooming and fecal pallet was significantly increased in the arsenite-exposed F1 female mice compared to the control. Downregulation of brain-derived neurotrophic factor (BDNF), serotonin receptor (5HT1A) and upregulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), interleukin 1 β (IL-1β), cyclooxygenase 2 (COX2), caspase-3, Bcl2-associated X protein (Bax) were detected in the prefrontal cortex in the arsenite-exposed F1 female mice. Microglial marker ionized calcium-binding adapter molecule 1 (Iba1)-positive cells were increased in the arsenite-exposed F1 female mice. Moreover, a significantly increased plasma corticosterone level was observed in the arsenic-exposed F1 female mice. This study suggested that gestational arsenic exposure induced anxiety-like behavior accompanied with dysregulation of neurological and immunological markers, neuroinflammatory responses, neuronal apoptosis, and decreased neurogenesis in the prefrontal cortex of F1 female mice.

Anxiolytic-like effects of citral in the mouse elevated plus maze: involvement of GABAergic and serotonergic transmissions.

Citral, a monoterpene which is a part of the essential oil of several medicinal plants, is generally regarded as safe for human and animal consumption. Studies have introduced citral as a functional component of some essential oils in anxiolytic and antidepressant therapies; however, the neuropharmacological characteristics of citral have not yet been reported. In the present study, we evaluated the anxiolytic activities of citral in comparison to two standard anxiolytics, diazepam and buspirone, in Swiss albino mice by intraperitoneal administration of 1, 2, 5, 10, and 20mg/kg using elevated plus maze (EPM) and open-field test (OFT). Moreover, we also examined whether the GABAA-benzodiazepine and 5-HT1A receptor are involved in the anxiolytic-like effects of citral by pretreatment with flumazenil and WAY-100635, respectively. Citral dose-dependently decreased the number of border crossings and time spent in borders, and also the number of grooming and rearing in OFT without altering the exploratory behavior of mice. In the EPM, this monoterpene led to a significant increase in number of entries in open arms and time spent in open arms, as well as a decrease in time spent in closed arms. Pretreatment with flumazenil and WAY-100635 both could reverse the anxiolytic effects of the citral in the EPM. These results suggest that anxiolytic activity of citral occurs via the GABAA and 5-HT1A receptor modulation.

Analysis of the effect of toxic chemicals on the physiological parameters of experimental animals

Titanium and its alloys are widely used in modern supersonic aircraft and rockets, submarines and ships, in the chemical and food industries, as well as in other areas of modern technology. In the process of obtaining titanium from ore, workers may be exposed to titanium metal dust (Ti) and titanium dioxide (TiO2), highly toxic chemical compounds – gaseous titanium tetrachloride (TiC14), its hydrolysis products, chlorine and phosgene vapors. The study of the influence of titanium produc-tion conditions on the body was carried out at the Ust-Kamenogorsk Titanium and Magnesium Plant (JSC UKTMP) of Kazakhstan, one of the largest enterprises for the production of titanium. To study the behavioral reactions of rodents under the influence of harmful components of the production of magnesium, titanium and their compounds, the «Open field» test was carried out. This test refers to methods that study conditionally unconditioned reflexes. Sexually mature white rats of the Wister line, weighing 180-220 g, were used as a model object; experimental animals were placed on the territory of three main workshops. The motor and emotional behaviors of experimental animals were studied. The assessment of motor activity indicators was determined using such indicators as locomotion and standing, and emotional activity was determined by the number of grooming and boluses (urination and defecation). As a result of the experiment, a unidirectional change in physiological parameters was revealed in animals that were on the territory of JSC «UK TMP» shops, and the quantitative characteristics of physiological processes were different – more pronounced in shop No. 1 (Shop «Magnesium») and less – in shop No. 3 (Shop «Titanium Sponge»).Key words: titanium-magnesium production; experimental animals, physical activity, emotional ac-tivity.

Yunnan Black Tea Flavonoids Can Improve Cognitive Dysfunction in Septic Mice by Activating SIRT1.

This study explored the effect and mechanism of Yunnan black tea flavonoids (YBTF) on cognitive dysfunction in septic mice. The mice were induced sepsis, the serum was determined using kits, and the tissue was determined by qPCR assay. The Yunnan black tea flavonoids were checked using HPLC. The test results showed that compared with the model group, YBTF could increase the survival rate of the mice; meanwhile, YBTF could also increase the total distance travelled, number of stands, and number of groomings, as well as the number of times crossing the area in the target quadrant. Detection of nerve cells showed that YBTF could reduce the rate of nerve cell apoptosis caused by sepsis. YBTF also reduced the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and malondialdehyde (MDA) in the hippocampus of septic mice and increased the activity of superoxide dismutase (SOD) and catalase (CAT) enzymes. YBTF could also upregulate the mRNA expression of SOD1, SOD2, CAT, and forkhead box O1 (FOXO1) and downregulate the mRNA expression of TNF-α, IL-1β, nuclear factor kappa-B (NF-κB), p53, and SIRT1 in the hippocampus of septic mice. The animal experiment results showed that YBTF could improve the cognitive dysfunction of septic mice. The effect of YBTF was weaker than that of dexamethasone, but it could enhance the improvement effect when used in conjunction with dexamethasone. The component analysis results showed that YBTF contained 9 compounds, including catechin, gallocatechin gallate, rutin, hyperoside, epicatechin gallate, dihydroquercetin, quercetin, myricetin, and sulphuretin. From these results, YBTF could activate SIRT1 through its active compound components to improve the cognitive dysfunction of septic mice.

Effects of notoginsenoside R1 on attenuating depressive behavior induced by chronic stress in rats through induction of PI3K/AKT/NF-κB pathway.

Chronic unpredictable mild stress (CUMS) can cause a series of depressive symptoms in depression patients. Recently, notoginsenoside R1 (NGR1) has been reported to play crucial roles in the anti-inflammatory, antioxidant, and anti-apoptotic. However, the role and mechanisms of NGR1 in improving symptoms of depressive behavior remain unknown. Evaluating and identifying its value and exploring the mechanisms of NGR1 on CUMS-induced depressive behavior were the aims of this study. Here, rats were separated into five different groups and treated with or without different concentrations of the NGR1. Then, the body weight, sucrose preference rate, immobility time, crossing number, rearing number, and grooming number were determined to evaluate the effect of NGR1 on improving the depressive behavior of CUMS rats. Subsequently, the morphology of hippocampal neurons and protein expression of brain-derived neurotrophic factor in each group were examined by hematoxylin and eosin staining and western blot to show the neuroprotective effects of NGR1. Furthermore, the mRNA and protein expression of TNF-α, IL-6, and IL-1β were also detected by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay to verify the anti-inflammatory effects of NGR1 on CUMS rats. In addition, the cell apoptosis-related proteins were examined to reveal that NGR1 can inhibit cell apoptosis in CUMS rats. Moreover, it was confirmed that NGR1 attenuated the symptoms of depressive behavior by mediated PI3K/Akt/NF-κB pathway. Together, this study shows that NGR1 improves depressive behavior induced by chronic stress in rats through activation of PI3K/AKT/NF-κB pathway.

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.

Complex effect of caffeine and dioxidine on behavioral responses in mice in Porsolt test

Relevance. In light of the popularization of the use of caffeine-containing products, the question of the combined use of caffeine with substances exhibiting a toxic effect remains open. The doses of caffeine, which have a pronounced antidepressant effect, are also insufficiently studied. The aim of the study was to study the effect of repeated administration of caffeine and dioxidine on the behavioral responses of mice in the Porsolt test. Materials and methods. The experiment was carried out on 36 outbred male mice, divided into 6 groups. Experimental groups for 15 days of the study received caffeine at a dose of 40 mg/kg (first) or 100 mg/kg (second), dioxidine at a dose of 200 mg/kg (third), together with caffeine 40 mg/kg or 100 mg/kg, and dioxidine (fourth and fifth groups, respectively). The animals of the control group were injected with saline. To study the behavior, the Porsolt test was carried out, evaluating the following indicators on the 1st, 8th and 15th days of the experiment: the total time of immobilization, active swimming, climb, the number of grooming and shaking off acts. Results . The administration of caffeine at a dose of 40 mg/kg caused an increase in the time of active swimming and a decrease in the duration of immobilization on the 8th and 15th days. When caffeine was used at a dose of 100 mg/kg, an increase in the time of active swimming was noted with a single exposure, with an experiment duration of 8-15 days, an increase in the duration of immobilization was observed. Dioxidine caused a significant decrease in the time of active swimming and an increase in the duration of immobilization during all days of the experiment. The combined use of caffeine (40 mg/kg and 100 mg/kg) and dioxidine on the 1st day led to a decrease in immobilization and the time of active swimming. In both groups, 100 % animal mortality was observed by the 15th day. Conclusion. The results of the study indicate the presence of an antidepressant effect in caffeine at a dose of 40 mg/kg on the 8th and 15th days of the experiment and the absence of this effect in caffeine at a dose of 100 mg/kg with a duration of administration of 8-15 days. The use of dioxidine led to the absence of antidepressant activity and the presence of the opposite effect. The combined administration of caffeine (40 mg/kg and 100 mg/kg) and dioxidine led to 100 % mortality in the experimental groups by the 15th day of the experiment

Sex-related differences in behavioural markers in adult mice for the prediction of lifespan.

Finding biomarkers to assess the rate of ageing and consequently, to forecast individual lifespan is a challenge in ageing research. We recently published a mathematical model for lifespan prediction in adult female mice using behavioural parameters such as internal locomotion and time spent in open arms in the hole board (HB) and elevated plus maze (EPM) tests, respectively. Nevertheless, it is still not known if these behavioural variables could be useful in forecasting lifespan in male mice. Therefore, two groups of ICR-CD1 mice, male and female were subjected to the EPM, HB and T-maze tests at the adult age. Mice were monitored until they died and individual lifespans were registered. In general, adult male mice showed more anxiety-like behaviours than females. The mathematical model previously developed in females was validated with the female cohort, but found to be suboptimal for lifespan prediction in males. Thus, a new model for male lifespan prediction was constructed including the behavioural variables that were predictive of lifespan in males: time in the central platform of the EPM, inner locomotion, number of groomings and number and duration of head-dippings in the HB. These results confirm that the higher the anxiety-like behaviour at the adult age, the shorter the lifespan.

Effect of glucocorticoid receptor function on the behavior of rats with attention deficit hyperactivity disorder

To investigate the ideal animal models for attention deficit hyperactivity disorder (ADHD) subtypes and the effect of glucocorticoid receptor (GR) function on the behavior of ADHD rats by comparing behavioral differences between spontaneously hypertensive rats (SHRs), Wistar Kyoto (WKY) rats, and Sprague-Dawley (SD) rats. A total of 24 male SHRs aged 21 days were randomly divided into GR agonist group, GR inhibitor group, and SHR group, with 8 rats in each group. Eight male WKY rats and 8 male SD rats, also aged 21 days, were enrolled as WKY group and SD group respectively. The GR agonist group was treated with intraperitoneal injection of dexamethasone (0.5 mg/kg daily); the GR inhibitor group was treated with intraperitoneal injection of mifepristone (RU486) (54 mg/kg daily); the SHR, WKY, and SD groups were treated with intraperitoneal injection of normal saline (0.5 mL/kg daily). The course of treatment was 14 days for all groups. The open field test and Lat maze test were used to evaluate spontaneous activity and non-selective attention. The open field test showed that before drug intervention the SHR group had significantly higher numbers of line crossings and rearings than the WKY and SD groups (P<0.05); the WKY group had a significantly higher number of line crossings than the SD group (P<0.05); the SD group had a significantly higher number of groomings than the WKY group (P<0.05). After drug intervention, the GR agonist group had significantly lower numbers of line crossings and groomings than the SHR group (P<0.05). The Lat maze test indicated that before drug intervention the SHR group had significantly higher numbers of corner crossings and rearings than the WKY and SD groups (P<0.05); the WKY group had significantly higher numbers of rearings and leanings than the SD group (P<0.05). After drug intervention, the GR agonist group had significantly lower numbers of corner crossings and rearings than the SHR group (P<0.05); the GR inhibitor group had a significantly higher number of rearings than the SHR group (P<0.05); the WKY group had significantly higher numbers of rearings and leanings than the SD group (P<0.05). SHR is an ideal animal model for mixed subtype ADHD, and further studies are needed to determine whether WKY rats can be used as an animal model for attention-deficit subtype ADHD. GR agonist can effectively improve spontaneous activity and non-selective attention in SHRs.

Cannabidiol regulates behavioural alterations and gene expression changes induced by spontaneous cannabinoid withdrawal.

Cannabidiol (CBD) represents a promising therapeutic tool for treating cannabis use disorder (CUD). This study aimed to evaluate the effects of CBD on the behavioural and gene expression alterations induced by spontaneous cannabinoid withdrawal. Spontaneous cannabinoid withdrawal was evaluated 12h after cessation of CP-55,940 treatment (0.5mg·kg-1 every 12h, i.p.; 7days) in C57BL/6J mice. The effects of CBD (5, 10 and 20mg·kg-1 , i.p.) on withdrawal-related behavioural signs were evaluated by measuring motor activity, somatic signs and anxiety-like behaviour. Furthermore, gene expression changes in TH in the ventral tegmental area, and in the opioid μ receptor (Oprm1), cannabinoid CB1 receptor (Cnr1) and CB2 receptor (Cnr2) in the nucleus accumbens, were also evaluated using the real-time PCR technique. The administration of CBD significantly blocked the increase in motor activity and the increased number of rearings, rubbings and jumpings associated with cannabinoid withdrawal, and it normalized the decrease in the number of groomings. However, CBD did not change somatic signs in vehicle-treated animals. In addition, the anxiogenic-like effect observed in abstinent mice disappeared with CBD administration, whereas CBD induced an anxiolytic-like effect in non-abstinent animals. Moreover, CBD normalized gene expression changes induced by CP-55,940-mediated spontaneous withdrawal. The results suggest that CBD alleviates spontaneous cannabinoid withdrawal and normalizes associated gene expression changes. Future studies are needed to determine the relevance of CBD as a potential therapeutic tool for treating CUD.

The behavioral study on the interactive aggravation between pruritus and depression.

BackgroundThe interactive aggravation of pruritus and depression is well‐known, but an appropriate experimental model that could mimic this behavioral phenomenon is still lacking. Thus, a systematic animal behavioral investigation was carried out in this study. This will promote the research and treatment of pruritus and depression.MethodsThe 2,4‐dinitrofluorobenzene (DNFB)‐induced chronic itch model was established to measure the depression index by forced swimming test (FST), tail suspension test (TST), and splash test (ST). The chronic unpredicted mild stress (CUMS)‐induced depression model was established to measure spontaneous itch and acute histamine or chloroquine‐induced itch behaviors. A depression and itch combining model was also established to measure the scratching and depression behaviors. The motor function of DNFB mice was analyzed by the rotarod test.ResultsThe scratching number, the immobility time in the FST and TST, and the grooming number in the ST test were all significantly increased in the chronic itch model. Mice receiving CUMS treatment showed significantly increased spontaneous scratching number, immobility time in the FST and TST tests, and grooming number in the ST. The combined model showed increased immobility time in FST and TST tests and increased grooming number in ST comparing to the depression model, and showed increased scratching number comparing to the chronic itch model. After histamine (His) or chloroquine (CQ) injection, the scratching numbers of CUMS mice were all significantly increased compared to those of His‐ and CQ‐control, respectively. Anti‐depression drug ketamine could significantly inhibit the depression‐like behaviors of CUMS mice, and simultaneously stopped the promoting effect on His‐induced acute itch.ConclusionsThis study established an appropriate cross aggravation experimental mode and demonstrated that there is cross aggravation between pruritus and depression. The illumination of related mechanisms underlying this cross aggravation effect will provide theoretical basis for the prevention and treatment of depression and pruritus.

Open-field behavioral study in rat hyperlipidemia combined with chronic unpredictable mild stress model

To investigate behavioral changes in a rat hyperlipidemia model induced by high lipid feed combined with depression by Chronic Unpredictable Mild Stress (CUMS). A total of 40 rats were randomly divided into control (CON), control feed for 9 weeks followed by CUMS for 4 weeks (CON + CUMS), high fat diet (HFD) and high lipid feed for 9 weeks followed by CUMS for 4 weeks (HFD + CUMS) (n = 10 each). Open-field test was individually measured at baseline, week 9 and week 13. (1) Serum lipids: total cholesterol [(2.67 ± 0.04) mmol/L, (2.68 ± 0.02) mmol/L] and low density lipoprotein [(1.08 ± 0.03) mmol/L, (1.06 ± 0.01) mmol/L] of HFD and HFD + CUMS were both significantly higher than those of CON and CON + CUMS [(1.78 ± 0.12) mmol/L, (0.79 ± 0.04) mmol/L; (1.76 ± 0.09) mmol/L, (0.76 ± 0.06) mmol/L, all P < 0.01]. (2) Open-field test: at week 13, compared to CON rats, CON + CUMS rats exhibited enhanced locomotor activity during the first minute, reduced activity in the center squares and rearing, and increased the number of grooming and defecation (all P < 0.05). In comparison to the CON rats, a decrease in total squares in 5 min, central squares and peripheral squares was observed in HFD rats at week 13 (all P < 0.05). However, compared with HFD, CON, CON + CUMS rats, when high lipid feed for 9 weeks combined with depression, significant decrease activities in total squares in 5 min, central squares and peripheral squares were observed in HFD + CUMS rats at week 13. Besides these, the number of rearing was reduced, however, locomotor activity during the first minute and the number of grooming and defecation was significantly increased (all P < 0.001). Under uncontrolled hyperlipidemia, severe depressive symptoms will present more early once exposure to a series of chronic stressors followed by significant autonomic nervous dysfunctional symptoms.

Anxiolytic-like effects of phytol: Possible involvement of GABAergic transmission

Phytol, a branched chain unsaturated alcohol, is particularly interesting because it is an isolated compound from essential oils of different medicinal plants. The aim of this study was to evaluate the anxiolytic-like effects of phytol in animal models to clarify their possible action mechanism. After acute intraperitoneal treatment with phytol at doses of 25, 50 and 75mg/kg behavioral models of open-field, elevated-plus-maze, rota-rod, light–dark, marble-burying and pentobarbital sleeping time tests were utilized. In open field test, phytol (25, 50 and 75mg/kg) [p<0.01] increased the number of crossings and rearings. However, the number of groomings [p<0.01] was reduced. Likewise, the number of entries and the time spent in light space were increased [p<0.01] while the number of marble-burying was decreased [p<0.001], in elevated-plus-maze, light–dark and marble-burying tests, respectively. In motor activity test, phytol (75mg/kg) impaired the rota-rod performance of mice [p<0.01]. In pentobarbital sleeping time test, phytol 75mg/kg decreased for latency of sleeping and phytol (25, 50 and 75mg/kg) increased the sleep time when compared to negative control [p<0.05]. All these effects were reversed by pre-treatment with flumazenil (2.5mg/kg, i.p.), similarly to those observed with diazepam (2mg/kg, i.p.; positive control) suggesting that the phytol presents mechanism of action by interaction with the GABAergic system. These findings suggest that acute administration of phytol exerts an anxiolytic-like effect on mice. Furthermore, suppose that phytol interacts with GABAA receptor, probably at the receptor subtypes that mediate benzodiazepines effects, to produce sedative and anxiolytic activities.

Acute treatment with the organochalcogen 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one produces behavioral changes and inhibition of creatine kinase activity in the brain of rats

Organotellurium compounds have been synthesized since 1840, but their pharmacological and toxicological properties are still incipient. Therefore, the objective of this study was to verify the effect of acute administration with the organochalcogen 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one on the activity of brain creatine kinase (CK), a key enzyme in energy metabolism, and on behaviors in the open field test of 30-day-old rats. Animals were treated intraperitoneally with a single dose of the organotellurium (125, 250, or 500 μg/kg body weight) and after 55 min of the drug administration the open field test was carried out. Behavior analyses were performed during 5 min and the number of the squares crossed, number of rearing, number of groomings and number of fecal boli were recorded by an observer. Then, the animals were sacrificed and the cerebral cortex, the hippocampus, and the cerebellum were dissected, and CK activity and sulfhydryl content were measured in the brain. The organotellurium increased the ambulation and rearing behaviors in the open field test at doses of 250 and 500 μg/kg. Moreover, the compound inhibited CK activity and provoked a reduced of thiol content measured by the sulfhydryl assay in all the tissues studied. Therefore, changes in energy homeostasis and motor behavior in rats treated with this organotellurium support the hypotheses that the brain is a potential target to pharmacological and toxicological effects of this compound.