Spontaneous Motor Activity In Mice Research Articles

C-Terminal-Dependent Control of EAAT2 Signaling, Corticostriatal Synaptic Glutamate Clearance and Spontaneous Motor Activity in Mice with Hypokinesia

Deficiency of the astrocytic excitatory amino acid transporter type 2 (EAAT2) and, consequently, inefficient glutamate clearance at corticostriatal synapses may contribute to the depression of self-initiated movements in Huntington’s disease (HD). Here we report that the removal of the last 68 amino-acids in the C-terminal of EAAT2 increases the levels of native EAAT2 in striatal lysates and counteracts some of the HD-related changes in the interactor spectrum of mYFP-tagged EAAT2. Using the Q175 mouse model of HD, we explored the functional consequences of C-terminal modifications. It was found that astrocytic expression of EAAT2-S506X or -4KR alleviates the HD-related decrease in the incidence and velocity of exploratory movements. It also stimulates astrocytic glutamate uptake, increases the level of synaptic EAAT2 and improves glutamate clearance at single corticostriatal synapse. The experiments illuminate a link between the intracellular regulation of astrocytic glutamate transport in the striatum and symptoms of hypokinesia in HD mice.

Effect of Psoralea corylifolia extract on physically induced depression in mice.

<p>The mouse forced swimming test (FST) and tail suspension test (TST) are widely used to predict anti-depressant efficacy indicated by immobility time to be reduced by several different classes of anti-depressant drugs. PCE feeding at the dose of 75,150 and 300 mg/kg reduced the immobility duration at 14-days and 21-days, however the decrease was significant in mice treated with PCE for 21-days also, extract had no effect on spontaneous motor activity in mice, indicating that extract had no excitatory or inhibitory action on central nervous system in effective dose range, which eliminated the probability of false-positive results in forced swimming test and tail suspension test. Interestingly, the dose-response effect of PCE on reduction of serum CRF levels was concomitance with that on increase of brain 5-HT contents, as well as on swimming increase, indicating that the serotonergic system and the HPA axis responds with the production of 5-HT and CRF profiles that is characteristic for PCE applied in the mouse FST. Our results demonstrate that the oral administration of PCE possesses an anti-depressant-like activity, as evidenced by behavioural studies. Detailed investigations are needed to fully elucidate the mechanism of action at cellular level for the bioactive constituents present in the extract. </p>

Development and Characterization of Thermosensitive intranasal Gel Containing Paliperidone Loaded Microspheres

Purpose: The objective of the present investigation was to fabricate a thermosensitive gel containing paliperidone loaded microspheres for the treatment of schizophrenia for brain delivery through nasal route. Incorporation of drug in to microspheres and then in to gel should increase the duration of release and nasal duration time respectively. Material and Method: Ethyl cellulose microspheres containing paliperidone palmitate were prepared by emulsification of ethyl acetate dispersion containing polymer and drug with aqueous external phase containing polysorbate 80. Amount of ethyl cellulose and polysorbate 80 were identified as critical formulation variables influencing the drug release at critical time points, percentage yield and particle size. These factors were studied using 2 factors and 3 level face centered factorial design using Design Expert ® . Drug-excipient compatibility was ascertained using FTIR analysis. The paliperidone microspheres were then incorporated in to Pluronic F127 and HPMC gel having required thermo sensitive and muco adhesive properties. Gel containing microspheres was subjected to Ex vivo permeation study, irritation study using sheep nasal mucosa and pharmacodynamic study (spontaneous motor activity in mice). Results: Microspheres that could sustain the drug release up to 8 hours were developed. Thermoreversible gel having required thermo sensitive and muco adhesive properties was developed. The Ex vivo permeation study and pharm a codynamic study of the drug loaded microsphere containing gel confirmed the release up to 8 hours. The histopathology study showed absence of irritation on sheep nasal mucosa. Conclusion: Paliperidone palmitate loaded microspheres containing gel could prolong and target the drug release to brain and therefore give prolonged and intense action. Key words: Nose to brain delivery, Paliperidone palmitate, Pharmacodynamic activity, Thermoreversible gel, Desirability index.

Synergistic Effect of Fragrant Herbs in Japanese Scent Sachets

The sedative activity of eight aromatic natural medicines that are traditionally used in Japanese scent sachets was examined using an open field test with mice. Galangal (Kaempferia galanga), patchouli (Pogostemon cablin), sandalwood (Santalum album), spikenard (Nardostachys chinensis), cinnamon (Cinnamomum cassia), clove (Syzygium aromaticum), star anise (Illicium verum), and borneol (Dryobalanops aromatica) distilled oils were used. These natural medicines have various pharmacological effects. For example, galangal has insecticidal activity and clove extracts possess strong total antioxidant activity. Aromatherapy, a well-known complementary medicine system that uses inhalation, has recently attracted much attention. The sedative activity of inhaled aromatic compounds or essential oils has been examined by measuring the spontaneous motor activity of mice in an open field test. The galangal, patchouli, sandalwood, spikenard, and borneol oils showed significant sedative effects. The effect was stronger for a mixture of the five oils than for any of the single oils. This suggests that the oil mixture may have synergistic activity. Sedative activity was not observed when inactive oils (cinnamon, clove, and star anise) were added to the mixture of the five active oils.

Pharmacological investigation of selected medicinal plants of Bangladesh

Purpose: To pharmacologically investigate the methanol and petroleum ether extracts of the plant leaves of Manilkara zapota (MZME and MZPE, respectively), Abroma augusta (AAME and AAPE, respectively) and Vitex negundo (VNME and VNPE, respectively).Methods: Analgesic and anti-diarrheal activities were assessed by acetic acid-induced writhing and castor oil-induced diarrhea in mice, respectively, while CNS depressant activity was evaluated using hole-cross and open-field method by observing the decrease in exploratory behavior and spontaneous motor activity in mice, respectively.Results: All the extracts exhibited good analgesic activity at a dose of 200 mg/kg with the following rank order of activity: MZME > MZPE > VNME > VNPE > AAME > AAPE. Analgesic activity was insignificant at 100 mg/kg dose except for VNPE (67.81 % inhibition). The extracts produced significant reduction in diarrheal episodes in mice at a dose of 400 mg/kg MZPE (highest protection: 80.3 %, p < 0.05) and VNME (lowest protection: 38.6 %, p < 0.001). The extracts demonstrated CNS depressant activity in a dose-dependent manner (p < 0.05 compared to the standard except for AAME and AAPE which showed insignificant activity).Conclusion: The results indicate that the traditional use of the investigated plants appears to be justified; however, further studies are required to unravel the underlying mechanisms of action.Keywords: Manilkara zapota, Abroma augusta, Vitex negundo, Analgesic, Central nervous system depressant, Anti-diarrhoeal

Relationship between behavioral despair and spontaneous motor activity in mice

Relationship between behavioral despair and spontaneous motor activity in mice

The effect of -phenethylamine upon spontaneous motor activity in mice: a dual effect on locomotor activity.

Abstract The effect of intraperitoneal injections of β-phenethylamine on spontaneous motor activity in mice has been examined. Doses 75 mg/kg and higher produced a biphasic type of activity. A first phase of increased activity occurred about 5 min after injection, and a second about 30 min after injection. Pharmacological examination of these curves showed the first peak to be an indirect effect requiring newly synthesized noradrenaline, while the second peak appeared to be caused by a direct action. Thus it was not affected by reserpine, α-methyldopa, protriptyline, desipramine, disulfiram or α-methyl-p-tyrosine. These results suggest that phenethylamine differs from amphetamine in its effect on spontaneous motor activity.

Effects of nicotine on motor co-ordination and spontaneous activity in mice

Abstract Doses of nicotine (0·2 and 0·4 mg/kg subcutaneously) which depress spontaneous activity, improve the ability of mice to remain on a rotating rod, indicating that the reduction in activity is not due to non-specific disruption of motor ability. The performance of rats trained to press a bar for water rewards is stimulated by small subcutaneous doses (0·05, 0·1 mg/kg) of nicotine; larger doses (0·2, 0·4 mg/kg) briefly reduce the rate of bar-pressing before increasing it (Morrison, 1967). The larger doses also depress spontaneous motor activity in mice (Morrison & Armitage, 1967). In the present experiments a rotating rod (Dunham & Miya, 1957) was used to test whether the depresssion of spontaneous activity caused by nicotine is a result of motor incapacity.

Effects of Retama raetam (Forssk.) Webb & Berthel. (Fabaceae) on the central nervous system in experimental animals

Retama raetam (Forssk.) Webb & Berthel. (Fabaceae), commonly known as ?raetam? or ?broom bush?, is a desert shrub that grows abundantly in North-African countries, Palestine and Syria. Traditionally, this plant has been used as an abortifacient, a purgative and a vermifuge. In the present study, the effect of the methanol (MeOH) extract of the aerial parts of R. raetam on the central nervous system (CNS) has been evaluated using a mice model. In the photoelectrical cell test, the extract of R. raetam (ERR) at a dose of 125 mg/kg body weight did not exhibit any effect on the spontaneous motor activity in mice. At a dose of 250 mg/kg body weight, ERR increased ambulatory movement, but had no effect on the non-ambulatory movement, while a dose of 375 mg/kg body weight decreased both ambulatory and non-ambulatory movements. The effect of ERR on the anxiety levels and behaviors of mice was investigated using the elevated plus-maze test. At doses of 125, 250 and 375 mg/kg body weight, ERR decreased anxiety levels without showing an effect on the total activity; it did not affect anxiety levels but increased the total activity; it increased anxiety levels and decreased the total activity, respectively. In the diazepam-induced sleep test, ERR increased the onset of sleep without affecting the duration of sleep at the dose of 250 mg/kg body weight. The dose of 375 mg/kg body weight decreased the onset of sleep while increasing the duration of sleep. ERR did not exhibit any effect on the diazepam-induced sleep in the presence of flumazenil or picrotoxin.

Synthesis and Analgesic-like Effect of (6R, 4S)-p-Mentha-1,8-dien-6-ylmethylene- p-toluenesulfonamide

The synthesis of a monoterpene-based para-toluenesulfonamide is reported starting from naturally occurring (R)- (−)-carvone (1), by 1,2-addition of HCN followed by reduction with lithium aluminum hydride to afford the amino alcohols 3a and 3b. Tosylation of thismixture with p-toluenesulfonyl chloride furnished sulfonamide 4 in 55% overall yield. Compound 4 was evaluated in behavior animal models to investigate its effects on the central nervous system. It showed low toxicity and sedative action in mice, indicating it to be psychoactive. It also caused a decrease in the spontaneous motor activity of mice. This depressant effect was confirmed in the acetic acid-induced writhing test, which demonstrated a significant antinociceptive response more potent than 1. The present results provide evidence that sulfonamide 4 has analgesic-like psychopharmacological activity.

Antidepressant-like effects of the ethanolic extract of Xiaobuxin-Tang, a traditional Chinese herbal prescription in animal models of depression

Xiaobuxin-Tang, a traditional Chinese herbal prescription recorded in a silk scroll unearthed from Mogao Caves of Dunhuang has been indicated that it can remit depressive disorder. The present study was designed to investigate its antidepressant effects in various animal depression models. Xiaobuxin-Tang was extracted by 70% alcohol, and then three behavioral despair models and 5-Hydroxytryptophan (HTP)-induced head twitch response model were adopted to assess the antidepressant effects of the ethanolic extract of Xiaobuxin-Tang with the study on spontaneous motor activity. Groups of mice and rats received oral treatment with Xiaobuxin-Tang (150 - 1200 mg/kg) only once acutely in all tests. The duration of immobility was measured during the last 4 minutes of the 6-minutes test period in mice forced swimming test, rats forced swimming test and mice tail suspension test. In 5-HTP-induced head twitch response, the mice were intraperitoneally administered with 120 mg/kg of L-5-HTP, and then the cumulative number of head twitches was counted in 20 minutes. Spontaneous motor activities of mice were recorded automatically in 10 minutes by VIDEOMEX-V image analytic system. The extract at doses of 300 mg/kg (p.o.) and 600 mg/kg (p.o.) significantly decreased the duration of immobility time in a dose dependent manner in mice forced swimming test; also, the extract at dose of 1200 mg/kg (p.o.) significantly decreased the duration of immobility time in rat forced swimming test. Furthermore, the extract at a dose of 600 mg/kg had the same effect in mice tail suspension test. Meanwhile, the extract at the effective doses for behavioral despair models, had no effect on spontaneous motor activity in mice. The extract (300 - 1200 mg/kg, p.o.) also increased the accumulative number of the 5-HTP-induced head twitch response in mice in 20 minutes. Our results suggested that the ethanolic extract of Xiaobuxin-Tang exerts antidepressant-like effect.

Synthesis, pharmacology and molecular modeling of N-substituted 2-phenyl-indoles and benzimidazoles as potent GABA A agonists

Among the known non-benzodiazepine hypnotic drugs, Zolpidem ( 1a), Indiplon ( 2a) and Zaleplon ( 2b) have shown high affinity and selectivity for the α 1 subunit of the GABA-A receptor. Our group has performed pharmacophoric and ADMET-prediction studies to evaluate a virtual library of new molecules based on privileged structures. Among these, we have synthesized a library of N-substituted indoles and a library of N-substituted benzimidazoles. Afterwards, in vitro screening and in vivo spontaneous motor activity in mice has revealed molecules with good in vitro affinities for the α 1 receptor and potent in vivo induction of sedation.

Evaluation of the Central Activity of Hydroxydihydrocarvone

The central effects of hydroxydihydrocarvone (HC), an analogue of several monoterpenes, were evaluated in animal models. General behavior, locomotor activity, pentobarbital-induced sleeping time, pentylenetetrazol (PTZ)-induced convulsions, and acetic acid-induced writhing were evaluated in mice. The compound caused palpebral ptosis, decreased the response to touch, and increased sedation (general behavioral profile). HC (50-200 mg/kg) caused a significant dose-dependent decrease in the spontaneous motor activity of mice. This compound (100, 200 mg/kg) potentiated the pentobarbital sleeping time, indicating a depressant action. HC also protected the mice against PTZ-induced convulsions at 400 mg/kg. In the acetic acid-induced writhing, the antinociceptive activity of HC was demonstrated with a significant dose-dependent response at a dose range of 25-400 mg/kg. The present results provide evidence that HC has significant psychopharmacologic activity with depressant effects.

Antianxiety effects of riparin I fromAniba riparia (Nees) Mez (Lauraceae) in mice

This work presents the behavioral effects of riparin I (methyl ether of N-benzoyl tyramine) from unripe fruit of Aniba riparia (Lauraceae) on the elevated plus maze, open field, rota rod and hole board tests in mice. Riparin I was administered acutely by intraperitoneal (i.p.) and oral routes to male mice at doses of 25 and 50 mg/kg. The results showed that riparin I (25 and 50 mg/kg, i.p. and per os) increased the number of entries and the time of permanence in the open arms in the plus maze test. Similarly, in the hole board test, riparin I in both routes increased the number of head dips. Riparin I with both doses and routes had no effects on spontaneous motor activity in mice or in the rota rod test, but decreased the number of groomings. These results showed that riparin I by both administration routes has effects on the central nervous system with antianxiety effects on the plus maze and hole board tests. The substance is devoid of myorelaxant effects.

Antianxiety and antidepressant effects of riparin III from Aniba riparia (Nees) Mez (Lauraceae) in mice

This work presents behavioral effects of methyl ethers of N-(2,6-dihydroxybenzoyl) tyramine (riparin III) isolated from the unripe fruit of Aniba riparia on the open field, elevated plus maze (EPM), rotarod, hole board, barbiturate-induced sleeping time, tail suspension and forced swimming tests in mice. Riparin III was administered intraperitoneally to male mice at single doses of 25 and 50 mg/kg. The results showed that riparin III with both doses had no effects on spontaneous motor activity in mice or in the rotarod test, but decreased the number of grooming and rearing. At the dose of 50 mg/kg, riparin III increased the number of entries in the open arms of the EPM test as compared with control. Similarly, in the hole-board test, both doses increased the number of head dips. There was a reduction on the sleeping latency with both doses and a prolongation of the pentobarbital-induced sleeping time with the dose of 25 mg/kg. In the tail suspension test, similar to imipramine (30 mg/kg), riparin III at the dose of 50 mg/kg presented a reduction in the immobility time. In the forced swimming test, both doses of riparin III decreased the immobility time. These results showed that riparin III potentiated the barbiturate-induced sleeping time and presented antidepressant- and anxiolytic-like effects.

Neuropharmacological Effects of Hibiscus sabdariffa Aqueous Extract

The neuropharmacological effects of the aqueous extract of Hibiscus sabdariffa (HS) calyx were studied in rodents. HS (100, 200 and 400 mg/kg, i.p.) caused a remarkable dose-dependent decrease in spontaneous motor activity in mice and increased the duration of pentobarbital (40 mg/kg, i.p.) induced sleep in rats. The extract (100-400 mg/kg, i.p.) significantly reduced the exploratory behaviour in mice. The extract significantly inhibited the intensity of apomorphine (1 mg/kg, s.c.) induced stereotypic behaviour and attenuated climbing in the mice dose-dependently. Similarly, chlorpromazine (3 mg/kg, i.p.) blocked apomorphine induced stereotype behaviour significantly. The intraperitoneal LD 50 of the extract was estimated to be greater than 5000 mg/kg. These results suggest that the aqueous extract of HS may contain psychoactive substances that are sedative in nature and which contribute to its use in traditional medicine as sedative.

Behavioural effects in rodents of methyl angolensate: a triterpenoid isolated from Entandrophragma angolense.

Behavioral effects of methyl angolensate were investigated in mice and rats. Spontaneous motor activity, pentobarbital sleeping time, amphetamine-stereotyped behaviour, exploratory activity and apomorphine-induced climbing studies in mice were evaluated. The results revealed that methyl angolensate reduced spontaneous motor activity in mice, prolonged the duration of pentobarbital sleeping time in rats and attenuated amphetamine-induced stereotype behaviour in rats. Methyl angolensate also decreased exploratory activity in mice and reduced the rate of apomorphine-induced climbing in mice at the doses tested. It is suggested that methyl angolensate possesses some biologically active principles that are sedative in nature.

The effect of Morinda officinalis How, a Chinese traditional medicinal plant, on the DRL 72-s schedule in rats and the forced swimming test in mice

The present study observed the antidepressant-like action of the medicinal plant Morinda officinalis in the differential reinforcement of low rate 72-s (DRL 72-s) schedule, a behavioral screen selective and sensitive to antidepressant drugs, and the forced swimming test, a well-known animal model of depression. In the DRL 72-s schedule in rats, the plant extract (25–50 mg/kg), similar to clinically effective antidepressant drug desipramine (5–10 mg/kg), significantly reduced response rate and efficiency ratio while at the same time increasing reinforcement rate. In the forced swimming test in mice, the plant extract (50 mg/kg), like the effect of desipramine (20 mg/kg), also elicited a significant reduction in the duration of immobility. A tendency to this phenomenon could be seen at the dose of 100 mg/kg. Meanwhile, the plant extract, in the effective doses for the forced swimming test, had no effects on spontaneous motor activity in mice. These findings provide further support for the conclusion that M. officinalis extract possesses the antidepressant effect.

Behavioral effects of the aqueous extract of Guiera senegalensis in mice and rats.

Behavioral effects of the aqueous extract of Guiera senegalensis on the central nervous system of mice and rats were investigated. Spontaneous motor activity, pentobarbital sleeping time, amphetamine-stereotyped behavior, exploratory activity and performance on treadmills (rota-rod) were evaluated. The results revealed that the aqueous extract of G. senegalensis reduced spontaneous motor activity in mice, prolonged the duration of pentobarbital sleeping time in rats and attenuated amphetamine-induced stereotype behavior in rats. The extract also decreased exploratory activity in mice and had no observable effects on motor coordination (rota-rod) at the doses tested. The results suggested that the crude aqueous extract of G. senegalensis possesses some biologically active principles that are sedative in nature.

Transforming growth factor-beta activated during exercise in brain depresses spontaneous motor activity of animals. Relevance to central fatigue

Intracerebroventricular administration into sedentary mice of the high molecular mass fraction of cerebrospinal fluid (CSF) from exercise-exhausted rats produced a decrease in spontaneous motor activity [K. Inoue, H. Yamazaki, Y. Manabe, C. Fukuda, T. Fushiki, Release of a substance that suppresses spontaneous motor activity in the brain by physical exercise, Physiol. Behav. 64 (1998) 185–190]. CSF from sedentary rats had no such effect. This suggests the presence of a substance regulating the urge for motion as a response to fatigue. A bioassay system using hydra, a freshwater coelenterate, showed an activity indistinguishable from transforming growth factor-beta (TGF-β) in the CSF from exercise-fatigued rats, while not in that from sedentary rats. The increase in the concentration of active TGF-β in the CSF from exercise-fatigued rat was also ascertained by another bioassay system using mink lung epithelial cells (Mv1Lu). Injection of TGF-β into the brains of sedentary mice elicited a similar decrease in spontaneous motor activity in a dose-dependent manner. Increasing the exercise load on rats raised both the levels of active TGF-β and the activity of depression on spontaneous motor activity of mice in the CSF of rats. Taken together, these results suggest that exercise increases active TGF-β in the brain and it creates the feeling of fatigue and thus suppresses spontaneous motor activity.