Neuroprotective Effects of P-Coumaric Acid on Haloperidol-Induced Catalepsy Through Ameliorating Oxidative Stress and Brain Dopamine Level

Objective To evaluate the effect of p-coumaric acid (p-CA) on haloperidol-induced catalepsy in Swiss albino male mice. Method To induce catalepsy, haloperidol (1 mg/kg i.p.) was administered for 21 consecutive days. p-CA (50, 75, and 100 mg/kg, PO) was administered 30 min before haloperidol injection for 21 consecutive days. For catalepsy, locomotor activity and motor coordination scores were recorded on the 17, 14, and 21 days of drug treatment, while the gait analysis score was recorded on day 21. After behavioral testing, animals were sacrificed, and various biochemical and histopathology tests of the brain were conducted. Dopamine, malondialdehyde, reduced glutathione (GSH), superoxide dismutase (SOD), and catalase activity were examined in the brain. Results Chronic administration of haloperidol significantly increased catalepsy in mice. It also produced hypolocomotion, motor coordination, and gait disturbance in mice. p-CA significantly inhibited haloperidol-induced catalepsy. Haloperidol significantly increased malondialdehyde levels in the brain. While dopamine levels in the brain dropped along with GSH, SOD, and catalase activity levels, which also had an impact on the histology of the brain. p-CA significantly reduced haloperidol-induced increases in brain oxidative stress, dopamine levels in the brain, and brain histology in mice. Discussion p-CA significantly reduced haloperidol-induced catalepsy, possibly through reducing oxidative stress and increasing brain dopamine levels. It can be a good candidate drug for extrapyramidal symptoms in Parkinson’s disease and adjuvant therapy with antipsychotic drugs.

Activation of a hypothalamus-habenula circuit by mechanical stimulation inhibits cocaine addiction-like behaviors

Background Mechanoreceptor activation modulates GABA neuron firing and dopamine (DA) release in the mesolimbic DA system, an area implicated in reward and substance abuse. The lateral habenula (LHb), the lateral hypothalamus (LH), and the mesolimbic DA system are not only reciprocally connected, but also involved in drug reward. We explored the effects of mechanical stimulation (MS) on cocaine addiction-like behaviors and the role of the LH-LHb circuit in the MS effects. MS was performed over ulnar nerve and the effects were evaluated by using drug seeking behaviors, optogenetics, chemogenetics, electrophysiology and immunohistochemistry. Results Mechanical stimulation attenuated locomotor activity in a nerve-dependent manner and 50-kHz ultrasonic vocalizations (USVs) and DA release in nucleus accumbens (NAc) following cocaine injection. The MS effects were ablated by electrolytic lesion or optogenetic inhibition of LHb. Optogenetic activation of LHb suppressed cocaine-enhanced 50 kHz USVs and locomotion. MS reversed cocaine suppression of neuronal activity of LHb. MS also inhibited cocaine-primed reinstatement of drug-seeking behavior, which was blocked by chemogenetic inhibition of an LH-LHb circuit. Conclusion These findings suggest that peripheral mechanical stimulation activates LH-LHb pathways to attenuate cocaine-induced psychomotor responses and seeking behaviors.

Comparative CNS activities of chlorpheniramine maleate, ebastine, and fexofenadine in Swiss albino mice

Background: Not all second-generation antihistamines were devoid of the central nervous system (CNS) effects such as cognitive and psychomotor impairment. Although these drugs penetrate blood–brain barrier (BBB) to lesser extent, many of them have been found to produce dose-related impairment of CNS functions with interdrug differences present among them. Aim and Objective: This study is aimed to analyze and compare the effects of different antihistamines (first and second generation) on the CNS using Swiss albino mice. Materials and Methods: Twenty-four Swiss albino mice of either sex weighing around 25 - 30 g were randomly divided into six groups with six in each group. Antihistamines such as chlorpheniramine maleate (CPM), ebastine, and fexofenadine were administered to respective groups through oral route. Their effects on CNS were evaluated using rotarod and actophotometer. The data were analyzed using statistical methods. Results: CPM produced significant reduction (P < 0.05) in motor coordination and spontaneous locomotor activity. Ebastine does not have any effect on motor coordination but significant reduction (P < 0.05) in spontaneous locomotor activity. Fexofenadine does not have any effect on motor coordination and spontaneous locomotor activity. Conclusion: We conclude that CPM has significant CNS depressant actions, ebastine has minimal CNS depressant actions, and fexofenadine does not have CNS depressant actions.

Knee extension strength and handgrip strength are important predictors of Timed Up and Go test performance among community-dwelling elderly women: a cross-sectional study

ABSTRACT BACKGROUND: Handgrip and knee extension strengths have each been used to characterize disability. However, it has been reported that the association between handgrip and knee extension strengths is weak. OBJECTIVE: To evaluate the influence of knee extensor and handgrip muscle strength on Timed Up and Go (TUG) test results among elderly women with worse (≥ 10 seconds) and better (< 10 seconds) performance, after controlling for confounders. DATA AND SETTING: Cross-sectional study on a sample selected according to convenience, carried out in a federal public institution of higher education. METHODS: Assessment of handgrip was carried out using the Jamar dynamometer (Lafayette Instrument Company, Inc., Lafayette, United States). Knee extensor muscle performance was measured using an isokinetic dynamometer (Biodex System 3 Pro; Biodex Medical Systems, Inc., United States), The confounding factors were education, age, comorbidities, body mass index and Geriatric Depression Scale and Human Activity Profile scores. Functional performance was assessed through the TUG test. A backward linear regression model was used. RESULTS: 127 elderly women performed the TUG test in more than 10 seconds and 93 in less than 10 seconds. However, regardless of test performance, handgrip strength and knee extension strength comprised the reduced final model. CONCLUSIONS: Knee extension strength and handgrip strength might be particularly useful indicators for measuring disability.

Melatonin decreases cocaine-induced locomotor activity in pinealectomized rats

Objective: Several studies have shown that the time of day regulates the reinforcing effects of cocaine. Additionally, melatonin and its MT1 and MT2 receptors have been found to participate in modulation of the reinforcing effects of such addictive drugs as cocaine. Loss of the diurnal variation in cocaine-induced locomotor sensitization and cocaine-induced place preference has been identified in pinealectomized mice. In addition, several studies in rodents have shown that administration of melatonin decreased the reinforcing effects of cocaine. The objective of this study was to evaluate the effect of melatonin on cocaine-induced locomotor activity in pinealectomized rats at different times of day (zeitgeber time [ZT]4, ZT10, ZT16, and ZT22). Methods: Naïve, pinealectomized Wistar rats received cocaine at different times of day. Melatonin was administered 30 min before cocaine; luzindole was administered 15 min prior to melatonin and 45 min before cocaine. After administration of each treatment, locomotor activity for each animal was recorded for a total of 30 min. Pinealectomy was confirmed at the end of the experiment through melatonin quantitation by ELISA. Results: Cocaine-induced locomotor activity varied according to the time of day. Continuous lighting and pinealectomy increased cocaine-induced locomotor activity. Melatonin administration decreased cocaine-induced locomotor activity in naïve and pinealectomized rats at different times of day. Luzindole blocked the melatonin-induced reduction in cocaine-induced locomotor activity in pinealectomized rats. Conclusion: Given its ability to mitigate various reinforcing effects of cocaine, melatonin could be a useful therapy for cocaine abuse.

Acupuncture improves locomotor activity and learning-memory ability by improving hippocampal cellular autophagy in rats with fetal intrauterine distress / 针刺研究

OBJECTIVE: To investigate the effect of acupuncture stimulation of head acupoints "Jin San Zhen" (JIN's Three Acupuncture Needles Therapy) on behavior reactions, hippocampal neuronal autophagy and expression of autophagy associated proteins (Beclin-1 and light chain 3 Ⅱ/Ⅰ [LC 3 Ⅱ/Ⅰ]) in rats with hypoxic-ischemic brain damage (HIBD) due to fetal intrauterine distress, so as to reveal its underlying mechanisms in improving neonatal HIBD. METHODS: Pregnant SD rats were used in the present study. The HIBD model was established by delayed caesarean delivery and bilateral uterine arteries clipping for 10 minutes. The HIBD rats were randomly divided into model group and acupuncture groups (n＝9 rats in each group). The other 9 rats delivered naturally were used as the normal control group. On day 14 after delivery, the neonatal rats in the acupuncture group received acupuncture stimulation of head acupoints ("Nao San Zhen""Nie San Zhen" and "Zhi San Zhen") by twirling each needle leftward and rightward for 10 times, once a day for 14 d. The open field test and Morris water maze test were used to determine the locomotive activity and spatial learning-memory ability, respectively. The ultrastructure and autophagosomes in the hippocampal neurons were observed by transmission electron microscope. The contents and expression levels of Beclin-1 and LC3 Ⅱ/Ⅰ in the hippocampus tissues were detected by flow cytometry and Western blot, separately. RESULTS: Compared with the normal control group, the time to go out of the central region of open field test, and the escape latency and duration of first platform-quadrant-crossing of spatial exploration of Morris water maze tests were significantly increased (P<0.01，P<0.05，P<0.001), and the total distance and number of activities in the central region, and the target quadrant resistance time and number of platform-cros-sing remarkably decreased in the model group (P<0.01, P<0.05), suggesting a decline of both locomotor activity and learning-memory ability after modeling. The expression level (%) of Beclin-1 protein and ratio of LC3 Ⅱ/Ⅰ proteins were considerably increased in the model group (P<0.01). Following acupuncture interventions, the locomotor activity and spatial learning-memory ability were obviously increased (P<0.05，P<0.01，P<0.001), and the expression of Beclin-1 protein and ratio of LC3 Ⅱ/Ⅰ were further up-regulated relevant to the model group (P<0.001). Moreover, ultrastructural observation showed serrated change of nuclear membrane and widened perinuclear space, vacuolization in the mitochondria, dilation of endoplasmic reticulum and increase of autophagosomes in the hippocampal neurons in the model group. These situations were relatively milder in the acupuncture group. CONCLUSION: Acupuncture of head acupoints of "JIN San Zhen" may increase locomotor activity and learning-memory abi-lity in rats with HIBD due to fetal intrauterine anoxia, which is closely with its effect in promoting hippocampal neuronal autophagy via up-regulating the expression of Beclin-1 and LC3 Ⅱ/Ⅰ.

Comparative Behavioral Correlation of High and Low-Performing Mice in the Forced Swim Test

Behavioral analysis in mice provided important contributions in helping understand and treat numerous neurobehavioral and neuropsychiatric disorders. The behavioral performance of animals and humans is widely different among individuals but the neurobehavioral mechanism of the innate difference is seldom investigated. Many neurologic conditions share comorbid symptoms that may have common pathophysiology and therapeutic strategy. The forced swim test (FST) has been commonly used to evaluate the “antidepressant” properties of drugs yet the individual difference analysis of this test was left scantly investigated along with the possible connection among other behavioral domains. This study conducted an FST-screening in outbred CD-1 male mice and segregated them into three groups: high performers (HP) or the active swimmers, middle performers (MP), and low performers (LP) or floaters. After which, a series of behavioral experiments were performed to measure their behavioral responses in the open field, elevated plus maze, Y maze, three-chamber social assay, novel object recognition, delay discounting task, and cliff avoidance reaction. The behavioral tests battery revealed that the three groups displayed seemingly correlated differences in locomotor activity and novel object recognition but not in other behaviors. This study suggests that the HP group in FST has higher locomotor activity and novelty-seeking tendencies compared to the other groups. These results may have important implications in creating behavior database in animal models that could be used for predicting interconnections of various behavioral domains, which eventually helps to understand the neurobiological mechanism controlling the behaviors in individual subjects.

An Efficient and Reliable Assay for Investigating the Effects of Hypoxia/Anoxia on Drosophila / 神经科学通报·英文版

Stroke is a leading cause of death worldwide. Up to one thousand potential drugs or interventions have been developed to treat stroke, out of which ~160 have gone on to clinical trials. However, none of them has been successful. New insights into the molecular and cellular mechanisms of ischemia-induced injury are needed for discovering new therapeutic targets. Recently, Drosophila has been used to uncover new hypoxia-related genes. In this study, we describe an efficient and reliable assay with a sophisticated apparatus for studying the effects of oxygen deprivation on flies. Using this assay, wild-type flies were exposed to an anoxic environment for varying lengths of time, then the cumulative death rate and mobility recovery were systematically analyzed. We found that anoxia for over one hour caused lethality. The cumulative death rate on day 5 after anoxia was linearly and positively correlated with the duration of anoxia, and reached 50% when the duration was 2.5 h-3 h. We also found that the mobility recovery in normoxia was slow, as the climbing ability remained largely unchanged 4 h-6 h after 2.5-h of anoxia. We suggest that 2.5 h-3 h of anoxia and 4 h-6 h of recovery before mobility analysis are appropriate for future use of the anoxia assay.

Reliability and validity of free software for the analysis of locomotor activity in mice / 영남의대학술지

BACKGROUND: Kinovea software that tracking semi-automatically the motion in video screen has been used to study motion-related tasks in several studies. However, the validation of this software in open field test to assess locomotor activity have not been studied yet. Therefore, this study aimed to examine the reliability and validity of this software in analyzing locomotor activities.METHODS: Thirty male Institute Cancer Research mice were subjected in this study. The results examined by this software and the classical method were compared. Test-retest reliability and inter-rater reliability were analyzed with Pearson's correlation coefficient and intraclass correlation coefficient (ICC). The validity of this software was analyzed with Pearson's correlation coefficient.RESULTS: This software showed good test-retest reliability (ICC=0.997, 95% confidence interval [CI]=0.975–0.994, p < 0.001). This software also showed good inter-rater reliability (ICC=0.987, 95% CI=0.973–0.994, p < 0.001). Furthermore, in three analyses for the validity of this software, there were significant correlations between two methods (Pearson's correlation coefficient=0.928–0.972, p < 0.001). In addition, this software showed good reliability and validity in the analysis locomotor activity according to time interval.CONCLUSION: This study showed that this software in analyzing drug-induced locomotor activity has good reliability and validity. This software can be effectively used in animal study using the analysis of locomotor activity.

The inhibitory effects of YZG-330/YZG-331 on central nervous system / 中国药理学通报

Aim To investigate the inhibitory effects of the novel compounds YZG-330 and YZG-331 in central nervous system. Methods The sedative effect was investigated by recording the spontaneous locomotor ac-tivity in mice. The hypnotic effect was evaluated by the latency and duration of the loss of righting reflex ( LORR) in the threshold dosage of sodium pentobarbi-tal treated mice. The two compounds induced the mice that had woken up after a threshold dosage pentobarbi-tal sodium to fall asleep again. The levels of GABA and Glu in brain were measured by HPLC-ECD. Re-sults The results showed that spontaneous locomotor activities decreased in YZG-330 (0.125, 0.5,2 mg·kg-1 ) treated mice and YZG-331 (1.25, 5, 20 mg· kg-1 ) treated mice. YZGs could extend the duration of the loss of righting reflex in threshold dosage of sodium pentobarbital treated mice, and significantly shorten sleep latency. YZGs were able to allow the mice that had woken up after a threshold dosage pentobarbital so-dium to fall asleep again. YZG-331 (40 mg·kg-1 ,i. g. ) could significantly increase GABA level in hypo-thalamus and cerebral cortex. The content of GABA had no significant change after YZG-330 ( 2 mg · kg-1 , ig. ) administration. Conclusions YZG-330 and YZG-331 have potent sedative and hypnotic effects. The efficacy of YZG-330 is stronger than that of YZG-331 , but the mechanism of two compounds sounds different.

Exercise Intervention Improving the Behavior function of the Rat Model of Parkinson's Disease by Slowing down the Loss of Dopamine in Striatum / 中国运动医学杂志

Objective To explore the effect of the treadmill exercise intervention on the behavior function and the concentration of dopamine in the striatum of the rat model of Parkinson's disease (PD).Methods Healthy male Sprague-Dawley rats were randomly divided into a sham operation quiet (Control) group,sham-operation+Exercise (Control + Ex) group,6-hydroxydopamine (6-OHDA) quiet (PD) group,and 6-OHDA+Exercise (PD + Ex) group.PD and PD + Ex groups were injected 6-OH-DA into the right medial forebrain bundle to establish the unilateral PD rat model,while the sham operation groups were injected the same amount of physiological saline at the same site.On the 7th days after modeling,the rats were subcutaneously injected Apo morphine for rotational behavior test to exclude those not meeting the requirements for the PD model.One week after the operation,the exercise group started treadmill training at the speed of 11 m/min,30 min/day and 5 days/week,for a total of four weeks.The locomotor activity of PD rats was evaluated using the open field test.The DA concentration in striatum was detected using micro dialysis high performance liquid chromatography and electrochemistry.The expression of tyrosine hydroxylase positive fiber in the striatum was assessed using the immunohistochemistry.Results Compared with the Control group,significant decrease was observed in the moving distance of PD and PD + Ex groups (P＜0.01),while significant increase was found of PD + Ex group compared with PD group after 3 and 4weeks of training (P＜0.01).Compared with the Control group,DA concentration in the striatal decreased significantly in PD and PD + Ex groups,but that of PD + Ex group increased significantly after 3 and 4weeks' training compared with the PD group (P＜0.01).Conclusion There is a highly positive correlation between the total moving distance and the DA concentration in the striatum of PD rats.The moving distance and the DA concentration both have changed "sequentially" with the prolongation of 6-OHDA and exercise intervention.The exercise intervention can reduce the DA loss of the striatum and improve the locomotor function of PD rats.It is presumed that the mechanism may be related to the neuroprotective effect of exercise,which can reduce the damage of 6-OHDA neurotoxin to DA neurons and promote their survival.

Zika infection decreases Aedes aegypti locomotor activity but does not influence egg production or viability

BACKGROUND Zika has emerged as a new public health threat after the explosive epidemic in Brazil in 2015. It is an arbovirus transmitted mainly by Aedes aegypti mosquitoes. The knowledge of physiological, behavioural and biological features in virus-infected vectors may help the understanding of arbovirus transmission dynamics and elucidate their influence in vector capacity. OBJECTIVES We aimed to investigate the effects of Zika virus (ZIKV) infection in the behaviour of Ae. aegypti females by analysing the locomotor activity, egg production and viability. METHODOLOGY Ae. aegypti females were orally infected with ZIKV through an artificial feeder to access egg production, egg viability and locomotor activity. For egg production and viability assays, females were kept in cages containing an artificial site for oviposition and eggs were counted. Locomotor activity assays were performed in activity monitors and an average of 5th, 6th and 7th days after infective feeding was calculated. FINDINGS No significant difference in the number of eggs laid per females neither in their viability were found between ZIKV infected and non-infected females, regardless the tested pair of mosquito population and virus strain and the gonotrophic cycles. Locomotor activity assays were performed regardless of the locomotor activity in ZIKV infected females was observed, in both LD and DD conditions. MAIN CONCLUSIONS The lower locomotor activity may reduce the mobility of the mosquitoes and may explain case clustering within households reported during Zika outbreaks such as in Rio de Janeiro 2015. Nevertheless, the mosquitoes infected with ZIKV are still able to disseminate and to transmit the disease, especially in places where there are many oviposition sites.

Acupuncture Intervention Improves Behavior Reactions and Learning-memory Ability in Post-traumatic Stress Disorder Rats / 针刺研究

OBJECTIVE: To observe the therapeutic effect of acupuncture in the treatment of post-traumatic stress disorder (PTSD)-induced abnormal behavior reactions and learning-memory ability in rats with traumatic injury. METHODS: Sixty male SD rats were randomly divided into control, model, model＋animal capturing (capturing), medication and acupuncture groups (n＝12 rats in each). The PTSD model was established by "electric shock plus incarceration" method. Acupuncture was applied to "Baihui" (GV 20), and unilateral "Neiguan" (PC 6), "Shenmen" (HT 7) and "Taichong" (LR 3) once daily for 12 days. The rats in the medication group were treated by gavage of Paroxetine Hydrochloride solution (0.42 mg/mL), once daily for 12 days. The open field test containing horizontal (crossing grid lines) and rearing tests was performed for examining the rats' locomotor activity and anxiety-like behavior; and location navigation (escape latency) and special probe tests (platform quadrant crossing times) of Morris water maze tasks were detected for assessing the rats' learning-memory ability. On day 12 of the experiments, the rats were submitted to 3 consecutive sessions of open field tests for observing the time of familiar objects (TF) and the time of novelty object (TN) of exploration in 5 min (an object-location and an object-recognition tasks), followed by calculating the discrimination index [DI＝(TN－TF)/(TN＋TF)x100%]. RESULTS: After modeling, compared with the control group, the numbers of crossed grids and rearing, and DI were significantly decreased (P0.05)．. CONCLUSION: Acupuncture can effectively reduce anxiety-like behavior and improve the impaired learning-memory ability in PTSD rats.

Is Forced Swimming Immobility a Good Endpoint for Modeling Negative Symptoms of Schizophrenia? - Study of Sub-Anesthetic Ketamine Repeated Administration Effects

ABSTRACT Immobility time in the forced swimming has been described as analogous to emotional blunting or apathy and has been used for characterizing schizophrenia animal models. Several clinical studies support the use of NMDA receptor antagonists to model schizophrenia in rodents. Some works describe the effects of ketamine on immobility behavior but there is variability in the experimental design used leading to controversial results. In this study, we evaluated the effects of repeated administration of ketamine sub-anesthetic doses in forced swimming, locomotion in response to novelty and novel object recognition, aiming a broader evaluation of the usefulness of this experimental approach for modeling schizophrenia in mice. Ketamine (30 mg/kg/day i.p. for 14 days) induced a not persistent decrease in immobility time, detected 24h but not 72h after treatment. This same administration protocol induced a deficit in novel object recognition. No change was observed in mice locomotion. Our results confirm that repeated administration of sub-anesthetic doses of ketamine is useful in modeling schizophrenia-related behavioral changes in mice. However, the immobility time during forced swimming does not seem to be a good endpoint to evaluate the modeling of negative symptoms in NMDAR antagonist animal models of schizophrenia.

Evaluation of Quality of life, Physical Activity and Nutritional Profile of Postmenopausal Women with and without Vitamin D Deficiency / Qualidade de vida, atividade física e perfil nutricional de mulheres na pós-menopausa com e sem deficiência de vitamina D

Abstract Introduction Vitamin D deficiency is associated with various diseases. Prevalent in Brazil, it can result from inadequate lifestyle habits. Objective To demonstrate that postmenopausal women with vitamin D deficiency have worse quality of health, expressed as worse quality of life, lower levels of physical activity, and worse nutritional profile. Methods Postmenopausal women answered questionnaires about physical activity and quality of life, provided a 24-hour food record, and had serum vitamin D levels measured. Results Among the more active women, those who perform a daily average of one hour of physical activity had vitamin D levels above 20 ng/mL (76.9%), and those, which expose themselves to sunlight, had vitamin D levels above 30 ng/mL (34.6%). Meanwhile the percentages for the women who are less physically active and less exposed to sunlight were 42.2% and 8.9% respectively. Being more active and more exposed to sunlight resulted in a lower fat percentage. Serum vitamin D levels were not correlated with quality of life. Conclusion Walking and gardening increased serum vitamin D levels and decreased the percentage of body fat. The limitations of the study prevented the impact of 25hidroxyvitamin D on the quality of life and nutritional aspects of the women from being evaluated.

Resumo Introdução A deficiência de vitamina D está associada a diversas doenças. Prevalente no Brasil, pode ser consequência de hábitos de vida inadequados. Objetivo Demonstrar que mulheres na pós-menopausa com hipovitaminose D têm pior qualidade de saúde, expressa por piores qualidade de vida, nível de atividade física e perfil nutricional. Métodos Mulheres na pós-menopausa responderam a questionários sobre atividade física, qualidade de vida, registro alimentar de 24 horas, e tiveram os níveis séricos de vitamina D medidos. Resultados Dentre as mulheres mais ativas, as que praticam em média 1 hora de atividade por dia apresentaram níveis de vitamina D superiores a 20 ng/mL (76,9%), e as que se expõem ao sol apresentaram níveis acima de 30 ng/mL (34,6 %). Já as mulheres menos ativas e menos expostas ao sol apresentaram respectivamente 42,2 % e 8,9%. Ser mais ativa e ter maior exposição solar significou ter menor percentual de gordura. O nível sérico de vitamina D não mostrou relação com a qualidade de vida. Conclusão Caminhada e jardinagem aumentam os níveis séricos de vitamina D e diminuem o percentual de gordura corpórea. As limitações do estudo não permitiram avaliar o impacto da 25-hidróxi-vitamina D na qualidade de vida e nos aspectos nutricionais das mulheres.

Effects of paliperidone on MK-801-induced hyperactivity and disruption prepulse inhibition in rats / 中国神经精神疾病杂志

Objective To investigate the effects of risperidone and its active metabolite, paliperidone (9-hydroxyrisperidone), on hyperactivity and deficient sensorimotor gating induced by MK-801 in rats. Methods Adult male Sprague-Dawley (SD) rats (n=96) were used in this study. The effects of risperidone (0.1 mg/kg) and paliperidone (0.05, 0.10 and 0.20 mg/kg) on MK-801-induced (0.40 mg/kg) hyperactivity were examined in 48 rats with with 8 animals per group.The effects of risperidone(0.5 mg/kg)and paliperidone(0.10,0.50,1.00 mg/kg)on MK-801-induced (0.25 mg/kg) deficit in prepulse inhibition (PPI) were examined in 48 rats with 8~10 animals per group. Results Risperidone (0.10 mg/kg) and paliperidone (0.05 mg/kg) diminished the MK-801-induced hyperactivity (P<0.05). But paliperidone (0.10, 0.20 mg/kg) group did not affect locomotor activity compared to the control group. Risperidone (0.10 mg/kg) and different doses of paliperidone (0.10, 0.50, 1.00 mg/kg) enhanced the PPI baseline in rats. However, only risperidone (0.10 mg/kg), but not paliperidone restored the MK-801-induced deficits in PPI. Conclusion Risperidone and paliperidone have different pharmacological actions on MK-801-induced hyperactivity and deficits in prepulse inhibition in rats, suggesting that pharmacological actions of paliperidone are different from those of risperidone, although paliperidone is the active metabolite of risperidone.

Hangover relieving effect of Sanghwang mushroom mycelium cultured in germinated buckwheat

The present study was performed to evaluate the hangover relieving effect of germinated buckwheat (GB) and Sanghwang mushroom mycelium cultured in GB (SGB). Both GB and SGB showed 1,1-diphenyl-2-picrylhydrazyl radical scavenging activities and significantly increased (p < 0.001) aldehyde dehydrogenase (ALDH) activities; up to 140% increase at concentrations of 16 µL/mL. Locomotor activity test results from alcohol-SGB and alcohol-GB groups showed improved motor activities over that of the alcohol-water group at 90 min post-administration. Both alcohol-GB and alcohol-SGB groups had significantly reduced (p < 0.001) alcohol (40.02 ± 33.38 µg/mL, 66.01 ± 22.04 µg/mL, respectively) and aldehyde (5.72 ± 0.47 µg/mL, 6.72 ± 1.70 µg/mL, respectively) concentrations in blood compared to those in the alcohol-water group (199.75 ± 33.83 µg/mL, 50.43 ± 13.88 µg/mL, respectively) at 90 min post-administration. Based on cDNA microarray analysis, expressions of ALDH genes ALDH1a7 and ALDH18a1 and cytochrome P450 (CY450) gene CYP4a30b were upregulated in the alcohol-GB and alcohol-SGB groups compared to levels in the control group. Overall, the results suggest that both GB and SGB have hangover relieving effects by reducing blood acetaldehyde levels. The molecular mechanisms may involve ALDH activation and upregulated expression of alcohol metabolism-related genes such as ALDH and CYP450.

Effect of ethanolic extract of Zingiber officinale Roscoe on Central Nervous System activity in mice.

Zingiber officinale Roscoe, commonly known as ginger, is a traditional herb used to treat various disorders. In this study, we evaluated potential pharmacological effects of ethanolic extracts of Z.Officinale with respect to central nervous system (CNS) activity in mice. Role of ethanolic extract of ginger on CNS activity in mice was studied using models of elevated plus maze test, barbiturate-induced sleeping time, tail suspension test, hot-plate and tail-flick test. Ginger extract was administered to mice at single doses of 50 and 200 mg/kg, perorally while diazepam (1 mg/kg), morphine (5 mg/kg) and imipramine (30 mg/kg) intraperitoneally were used as standard drugs. The results showed that the ginger extract at all dose levels significantly exhibited anxiolytic activity increased the sleeping latency but reduced the sleeping time. Tail suspension test showed that the extract at both the doses was able to induce a significant decrease in the immobility time, similar to imipramine, a recognized antidepressant drug. Tail-flick and hot-plate tests demonstrated antinociceptive property of ginger extract, similar to morphine, a recognized antinociceptive agent. Higher dose level (200 mg/kg) showed better protective effects. Phytochemical screening of ethanolic extract revealed the presence of various phytoconstituents such as phenolic compounds, flavonoids, tannins, anthocyanins, carbohydrates, glycosides, proteins, resins and volatile oils. The possible mechanism by which ginger exhibited the significant beneficial effects on various CNS models in mice could be attributed to its antioxidant potential.

Evaluation of the sedative and hypnotic effects of H057 / 中国药理学通报

Aim To investigate the sedative and hyp-notic effects of a novel compound H057 . Methods The sedative activity of H057 was investigated by re-cording the spontaneous locomotor activity in mice. The hypnotic property was evaluated by the latency and duration of loss of righting reflex( LORR) in mice and effect of H057 on the sleep onset in subthreshold dos-age of sodium pentobarbital treated mice. The extracel-lular levels of GABA and monoamine neurotransmitters in in cerebral cortex were measured by microdialysis in vivo. Results The spontaneous locomotor activity was decreased by 25% and 66% in H057 ( 5 , 25 mg · kg-1 ,i. p. ) treated mice, respectively. H057 ( 3, 5 mg·kg-1 ,i. p. ) increased the sleep onset to 62. 5%and 87. 5% in subthreshold dosage of sodium pentobar-bital(25 mg·kg-1,i. p. ) treated mice. H057(≥60 mg· kg-1 , i. p. ) could completely induce LORR in mice. The latency of LORR at dose of 60 mg · kg-1 was (24 ± 11) min and the duration of LORR was (96 ± 15 ) min. In vivo mircodialysis revealed that H057 (25 mg·kg-1 , i. p. ) could significantly increase the GABA level by 26% and decrease the 5-HT and NE levels by 50% and 38% in cerebral cortex in mice. Conclusion H057 has potent sedative and hypnotic effects, which may be closely related to the increased content of GABA and the decreased contents of 5-HT and NE in the extracellular fluid in cerebral cortex.

Effects of scallop shell extract on scopolamine-induced memory impairment and MK801-induced locomotor activity

OBJECTIVE@#To evaluate the neuroprotective effects of the organic components of scallop shells (scallop shell extract) on memory impairment and locomotor activity induced by scopolamine or 5-methyl-10,11-dihydro-5H-dibenzo (a,d) cyclohepten-5,10-imine (MK801).@*METHODS@#Effect of the scallop shell extract on memory impairment and locomotor activity was investigated using the Y-maze test, the Morris water maze test, and the open field test.@*RESULTS@#Scallop shell extract significantly reduced scopolamine-induced short-term memory impairment and partially reduced scopolamine-induced spatial memory impairment in the Morris water maze test. Scallop shell extract suppressed scopolamine-induced elevation of acetylcholine esterase activity in the cerebral cortex. Treatment with scallop shell extract reversed the increase in locomotor activity induced by scopolamine. Scallop shell extract also suppressed the increase in locomotor activity induced by MK801.@*CONCLUSIONS@#Our results provide initial evidence that scallop shell extract reduces scopolamine-induced memory impairment and suppresses MK-801-induced hyperlocomotion.