Psychotropic effects of glutamic acid diethyl ester in mice

In 1 hour after intraperitoneal injection glutamic acid diethyl ester (GED) in doses 200 and 500 mg/kg decreased locomotor activity and exploratory patterns of mice in "open field" test. GED in doses 100 and 200 mg/kg diminished the immobilization period of animals in forced swimming test, that proves the reversal interaction of glutamatergic and catecholaminergic systems in CNS. Glutamate receptors antagonist--GED in doses 100-200 mg/kg disrupted passive avoidance reaction at 30 min before acquisition and retrieval, therefore glutamate receptors are involved into fixation and retrieval of memory engram.     

Neurobehavioral responses in swiss albino mice induced by an aqueous leaf extract from a medicinal plant named Heliotropium incanum Ruiz & Pav.

It is of interest to examine the adverse neuro-behavioural responses on mice treated with the aqueous crude extract of Heliotropium incanum (AEHI), which were evaluated using various behavioral paradigms. On the basis of median lethal dose value, doses of AEHI were chosen to be 150mg/kg and 440mg/kg for further experiment. Four groups comprising of five mice each were divided for the 14 days experiment. Group I, the control group, received distilled water; Group II and III received AEHI (150 mg/kg body weight and 440 mg/kg body weight) respectively; Group IV received standard drugs, Diazepam/Fluoxetine, administered orally. On administration of AEHI, it was revealed that dose 440 mg/kg showed less exploration activity in the hole board test; decrease in the number of squares crossed in locomotory test, time period in the open arm in the plus maze test was significantly reduced and the immobility time was significantly extended in comparison to control and standard drugs. The microscopic study of brain revealed damaged hippocampus along with nerve cells degeneration. Consequently, the results concluded that the outcome of the AEHI produced evidences for the anxiogenic activity in mice.     

Studies on the psychopharmacological activities of Rumex nepalensis Spreng. root extract in rats and mice.

The methanol extract of Rumex nepalensis Spreng. (Family - Polygonaceae) was assessed for different psychopharmacological activities in rats and mice by evaluation of general behaviour, exploratory behaviour, muscle relaxant activity and phenobarbitone sodium-induced sleeping time. The extract at doses 200 mg/kg and above exhibited a reduction in spontaneous activity (general behavioural profile), a decrease in exploratory behavioural pattern in the Y-maze and Head-dip tests, a reduction in muscle relaxant activity in rotarod, 30 degrees inclined screen and traction tests, and also potentiated phenobarbitone sodium-induced sleeping time.     

Central effects of citral, myrcene and limonene, constituents of essential oil chemotypes from Lippia alba (Mill.) n.e. Brown.

Citral, myrcene and limonene (100 and 200 mg/kg body wt., i.p.), constituents of essential oils from Lippia alba chemotypes, decreased not only the number of crossings but also numbers for rearing and grooming, as measured by the open-field test in mice. Although muscle relaxation detected by the rota rod test was seen only at the highest doses of citral (200 mg/kg body wt.) and myrcene (100 and 200 mg/kg body wt.), this effect was observed even at the lowest dose of limonene (50 mg/kg body wt.). Also, citral and myrcene (100 and 200 mg/kg body wt.) increased barbiturate sleeping time as compared to control. Limonene was also effective at the highest dose, and although citral did not increase the onset of sleep, it increased the duration of sleep, which is indicative of a potentiation of sleeping time. Citral (100 and 200 mg/kg body wt.) increased 2.3 and 3.5 times, respectively, the barbiturate sleeping time in mice. Similar effects were observed for myrcene and limonene at the highest dose (200 mg/kg body wt.) which increased the sleeping time around 2.6 times. In the elevated-plus maze, no effect was detected with citral up to 25 mg/kg body wt., while at a high dose it decreased by 46% the number of entries in the open arms. A smaller but significant effect was detected with limonene (5 mg/kg body wt.). While myrcene (10 mg/kg body wt.) decreased only by 22% the number of entries in the open arms, this parameter was decreased by 48% at the highest dose. Our study showed that citral, limonene and myrcene presented sedative as well as motor relaxant effects. Although only at the highest dose, they also produced a potentiation of the pentobarbital-induced sleeping time in mice, which was more intense in the presence of citral. In addition, neither of them showed an anxiolytic effect, but rather a slight anxiogenic type of effect at the higher doses.     

Effects of Anesthetic Ketamine on Anxiety-Like Behaviour in Rats

There is scarce information regarding the effects of anesthetic doses of the non-competitive N-methyl-d-aspartate receptor antagonist ketamine on anxiety. The current study evaluated the acute effects of intraperitoneally (i.p.) administered anesthetic ketamine (100 mg/kg) i.p. on anxiety in rats. For this purpose, the light/dark and the open field tests were utilized. The effects of anesthetic ketamine on motility were also examined using a motility cage. In the light/dark test, anesthetic ketamine, administered 24 h before testing reduced the number of transitions between the light and dark compartments and the time spent in the light compartment in the rats compared with their control cohorts. In addition, ketamine was found to exert a depressive effect on rats’ motility. In the open field test, animals treated with anesthetic ketamine 24 h before testing spent essentially no time in the central area of the apparatus, decreased horizontal ambulatory activity, and preserved to a certain extent their exploratory behaviour compared to their control counterparts. The results suggest that, in spite of its hypokinetic effect, a single anesthetic ketamine administration apparently induces an anxiety-like state, while largely preserving exploratory behaviour in the rat. These effects were time-dependent they since they were extinguished when testing was carried out 48 h after anesthetic ketamine administration.

     

Altered response of strain of Schistosoma mansoni to oxamniquine and praziquantel

The susceptibility of a fourth generation Ouh strain (Paranapanema Valley, S?o Paulo, Brazil) of Schistosoma mansoni to oxamniquine (OXA) and praziquantel (PZQ) was studied. Ten groups of 13 female albino mice each were infected with 70 cercariae per animal. These mice were medicated orally on the 50th day after infection. Five groups were given OXA doses of 0, 100, 200, 300 and 400 mg/kg (single doses) and the rest were treated with PZQ doses of 0, 100, 200, and 250 mg/kg/5 days. Each group was sub-divided: 8 animals underwent perfusion after 15 days treatment, 5 mice followed up for oviposition and their feces were tested every 15 days for miracidia hatching. The efficacy of the OXA doses of 100 and 200 mg/kg was 66% and 91.4%, respectively and for the 100 mg/kg PZQ dose it was 90.1%. The follow-up groups with 100 and 200 mg/kg of OXA and PZQ, 100 and 150 mg/kg, showed that they re-established the oviposition after a period of 60 to 75 days of treatment. The ED50 was 69.6 mg/kg OXA and 39.4 mg/kg PZQ. The results show the tolerance of the Ouh strain to a dose of 100 mg with both drugs and they appoint the need for a dose review during the follow up of the oviposition and in monitoring phenomena in the field.     

Asparagus racemosus Attenuates Anxiety-Like Behavior in Experimental Animal Models

Asparagus racemosus Linn. (AR) is used worldwide as a medicinal plant. In the present study, the anxiolytic activity of standardized methanolic extract of root of AR (MAR) was evaluated in open-field test (OFT), hole-board, and elevated plus maze (EPM) tests. Rats received oral pretreatment of MAR in the doses of 50, 100, and 200 mg/kg daily for 7 days and then were evaluated for the anxiolytic activity in different animal models. Both MAR (100 and 200 mg/kg) and diazepam (1 mg/kg, p.o.) increased the grooming behavior, number of central squares crossed, and time spent in the central area during OFT. Further, MAR (100 and 200 mg/kg) increased the head-dip and head-dip/sniffing behavior, and decreased sniffing activity in hole-board test. Furthermore, MAR (100 and 200 mg/kg) increased the percentage entries and time spent to open arm in EPM test paradigm. The anxiolytic activity in the experimental models was similar to that of diazepam. MAR (100 and 200 mg/kg) enhanced the level of amygdalar serotonin and norepinephrine. It also increased the expression of 5-HT_2A receptors in the amygdala. In another set of experiment, flumazenil attenuated the anxiolytic effect of minimum effective dose of MAR (100 mg/kg) in OFT, hole-board, and EPM tests, indicating GABA_A-mediated mechanism. Moreover, the anxiolytic dose of MAR did not show sedative-like effect in OFT and EPM tests compared to diazepam (6 mg/kg, p.o.). Thus, the anxiolytic response of MAR may involve GABA and serotonergic mechanisms. These preclinical data show that AR can be a potential agent for treatment of anxiety disorders.     

Effect of hydroxyurea on neural tube defects in the curly-tail mouse

Around 60% of curly-tail mice spontaneously develop neural tube defects (NTD), that is, exencephaly, and/or spina bifida (open lesions), or a curly tail (closed lesion), due to an incompletely penetrant recessive gene. Various doses of hydroxyurea, a teratogen to the rodent central nervous system, were administered to curly-tail mice on either day 8 or day 9 of pregnancy in an attempt to increase the number of NTD in the embryos. No dose used on either day achieved this. However, on day 8, the proportion of affected mice with open lesions increased from around 30% in control mice to 78% with 400 mg/kg hydroxyurea, and this was accounted for specifically by the production of exencephaly. When administered on day 9, 400, 500, and 600 mg/kg hydroxyurea (the latter two doses being lethal to embryos on day 8) actually reduced the incidence of total NTD, to around 30%. Among these affected mice, even though reduced in number, there was still a slight tendency for an increase in the number of exencephalics. Hydroxyurea also produced gastroschisis in a small percentage of embryos; the greatest incidence was 36% with 400 mg/kg on day 8.     

Effect of psychotropic preparations on the behavior of inbred mice under emotional stress]

The effect of phenazepam and sydnocarb in doses of 0.05, 0.07 and 0.1 mg/kg or 6, 12 and 24 mg/kg, respectively, on the behaviour of C57BL/6, CBA and BALB/c mice, was studied in the "open field" test. Interlinear difference in the reaction of inbred animals to emotional stress and its phenazepam or sydnocarb correction were established.     

二甲双胍对D-半乳糖诱导雄性中年小鼠衰老的干预作用*

目的:探讨二甲双胍(Met)对D-半乳糖(D-gal)诱导雄性中年小鼠衰老的干预作用。方法:50只ICR 9月龄雄性小鼠,在SPF级实验环境饲养,自由摄食与饮水。随机分5组:对照组,模型组,二甲双胍低、中、高剂量(Met 50 mg/kg,Met 100 mg/kg,Met 200 mg/kg)组,每组10只。Met组和模型组小鼠每日颈背部皮下注射D-gal 100 mg/ kg,同时分别给予Met(50、100、200 mg/kg)或等体积NS灌胃。对照组注射和灌胃等体积NS。连续8周给药。检测小鼠一般状态,体重,空腹血糖,血清和肝脏超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量水平;水迷宫实验检测学习记忆能力;HE染色观察小鼠海马组织结构。结果:每日Met 200 mg/kg干预,能减少模型小鼠的体重。Met干预对模型鼠正常空腹血糖无影响。每日Met 50、100、200 mg/kg剂量干预,与模型组相比,均能显著提升模型小鼠血清和肝组织的SOD活性(P＜0.05)、降低血清MDA含量(P＜0.05),改善学习记忆能力测试的大部分指标(P＜0.05),HE染色显示海马齿状回核固缩、深染的神经元明显减少。Met干预在大部分指标上呈剂量-效应依赖关系。结论:每日Met 50～200 mg/kg长期处理,以Met 200 mg/kg为显著,能延缓D-gal 诱导的雄性中年衰老模型小鼠的衰老进程,机制可能与降低小鼠体重与增强机体抗氧化水平有关。     

Behavioral effects of sinomenine in murine models of anxiety

The present study was designed to investigate the putative anxiolytic-like effect of sinomenine in three experimental models of anxiety in male rats and mice. Use of the elevated plus-maze test revealed that sinomenine (20 and 40 mg/kg, p.o.) increased the percentage of open arm entries and diazepam (2 mg/kg, p.o.) increased the percentage of open arm entries, the percentage of time spent on open arms and total arm entries in mice. In the light/dark transition test, sinomenine (20 and 40 mg/kg, p.o.) increased time spent in the light area and diazepam (2 mg/kg, p.o.) increased time spent in the light area and the overall movements in mice. In the social interaction test, the sinomenine-treated animals significantly increased social interaction time in low light unfamiliar (7 mg/kg, p.o.) and high light unfamiliar conditions (7 and 14 mg/kg, p.o.) as well as diazepam (3 mg/kg, p.o.). Sinomenine (28 mg/kg, p.o.) can also decrease squares entered in rats in social interaction test under low light unfamiliar condition. In the open-field test, sinomenine (160 mg/kg) decreased squares entered in mice. Thus, these findings indicated that sinomenine exhibited anxiolytic-like effect.     

Piplartine, an amide alkaloid from Piper tuberculatum, presents anxiolytic and antidepressant effects in mice

In the present work, we studied the effects of piplartine (PIP), an amide alkaloid isolated from the roots of Piper tuberculatum (Piperaceae), in the elevated plus maze, open field, rota rod, pentylenetetrazole (PTZ)-induced seizures, and forced swimming tests, in mice (Swiss, male, 25 g) to assess anxiolytic, sedative, muscle relaxant, anticonvulsant and antidepressant effects, respectively. Results showed that PIP (50 and 100 mg/kg, i.p.), similarly to diazepam, significantly increased not only the number of entrances (100% and 66%, respectively) but also the time of permanence in the open arms (104% and 199%, respectively), indicating that PIP presents an anxiolytic activity. Both effects were completely blocked by the previous administration of flumazenil what suggests the involvement of benzodiazepine type receptors. In the open field test, although PIP did not alter the number of crossings, it significantly increased grooming (103% and 119%) and rearing (60% and 23%), at the doses of 50 and 100 mg/kg respectively, as compared to controls. However, in the rota rod test, PIP was devoid of effect. Although in the PTZ-induced convulsion test, PIP did not alter the latency time for the onset of the first convulsion, as compared to controls, it significantly reduced in 58% and 60%, respectively, the animal's latency time to death. Furthermore, a significant and dose-dependent decrease in the immobility time, as evaluated by the forced swimming test, was observed after PIP administration (41% and 75% decrease, at the doses of 50 and 100 mg/kg, respectively), suggesting an antidepressant effect, similarly to that observed with imipramine, a classical antidepressant drug used as standard. In conclusion, we showed that PIP presents significant anxiolytic and antidepressant activities, making this drug potentially useful in anxiety and depression.     

Haloperidol-stomach lesions attenuation by pentadecapeptide BPC 157, omeprazole, bromocriptine, but not atropine, lansoprazole, pantoprazole, ranitidine, cimetidine and misoprostol in mice

The focus was on haloperidol (central dopamine antagonist)-stomach lesion, a longly described suitable counterpart of dopamine blocker cysteamine-duodenal lesion. In this, the contribution of blockade of central/peripheral dopamine receptors and prostaglandins synthesis, along with influence of antiulcer agents was evaluated in mice. Male NMRI Hannnover mice were sacrificed 24 h after haloperidol (25 mg/kg b.w. i.p., given alone or with saline (haloperidol+saline) (i) or in combination (ii,iii)). Supporting central dopamine predominance for haloperidol stomach lesion induction, co-administration of peripheral dopamine receptor antagonist domperidone (5 mg/kg i.p.) (haloperidol+ domperidone) (ii), or prostaglandin synthesis inhibitor indomethacin (10 mg/kg s.c.) (haloperidol+ indomethacin) (iii) did not aggravate this lesion. (i) In haloperidol+saline challenged mice the lesions were inhibited by co-administration (/kg i.p.) of a gastric pentadecapeptide BPC 157, GlyGluProProProGlyLysProAlaAspAspAlaGlyLeuVal, M.W. 1419 (10 microg, 10 ng, 10 pg, but not 1 pg, 100 fg, 10 fg), bromocriptine (10 mg), omeprazole (10 mg, 100 mg, but not 1 mg). Atropine (10, 100, 200 mg), pirenzepine (10, 100, 200 mg), misoprostol (10, 100, 200 microg), pantoprazole (1, 10, 100 mg), lansoprazole (0.1, 1, 10 mg), cimetidine (10, 100, 200 mg) and ranitidine (10, 100, 200 mg) were not effective. (ii) Dopamine peripheral blockade influence: in haloperidol+domperidone mice, previously effective bromocriptine, pentadecapeptide BPC 157 (10 microg) or omeprazole (10 mg) did not attenuate stomach lesions. (iii) Prostaglandins synthesis blockade effect: in haloperidol+indomethacin mice, previously effective agents, bromocriptine or omeprazole were not active, while BPC 157 effect was only lessened.     

Toxoplasma encephalitis: influence of the vehicle on the efficacy of different doses of 2',3'-dideoxyinosine in mice

In this study we investigated the effect of the antiretroviral molecule 2',3'-dideoxyinosine (Videx) against cerebral cysts in a murine model of toxoplasmic encephalitis caused by a wild cystic strain of Toxoplasma gondii. The role of the vehicle was also studied. Three doses were used: 50, 100 and 150 mg/kg of body weight/day. The doses of 50 and 150 mg/kg were prepared by dissolving pure 2',3'-dideoxyinosine powder in Maalox suspension before gavaging the mice; the dose of 100 mg/kg was prepared by grinding tablets of Videx that were suspended in water. A decrease in the number of cysts and a morphological modification of them were noted from day 15 with the lowest dose. The most important decrease could be observed with the dose of 100 mg/kg/d. After 30 days of treatment with this dose, 65% of the cysts were destroyed compared to controls. For the doses of 50 and 150 mg/kg/d prepared with Maalox, 36% and 51% of the cysts were destroyed respectively. So ddI has an effect on the cerebral cysts of T. gondii even at a low dose. The galenic formulation influences its action since the doses prepared with Maalox were less efficient than those prepared from ground tablets.     

Catecholaminergic component of the action of a heptapeptide analog of ACTH4-10 on the open-field behavior of rats

Heptapeptide Met-Glu-His-Phe-Pro-Gly-Pro (ACTH4-10 analog) at a dose of 0.015 mg/kg failed to alter open field behaviour of rats in the first test series. The peptide abolished amphetamine-induced stimulation of the exploratory and grooming behaviour. Extinction of the rats' exploratory behaviour during second test series in the open field (7 days later) was disturbed when haloperidol or apomorphine were injected before the first test series. When the peptide was administered with haloperidol or apomorphine, the extinction tended to become normal. Heptapeptide failed to change noradrenaline, dopamine or 5-hydroxytryptamine content in the rat forebrain. However, this peptide at a concentration of 10(-4) M moderately diminished tyrosine hydroxylation velocity in the rat striatal or hypothalamic synaptosomes, the effect depending on tyrosine concentration. These data suggest the involvement of catecholaminergic component into the heptapeptide action on the behaviour of rats.     

Cytogenetic effects of ribavirin on mouse bone marrow

The micronucleus test and mitotic chromosome analysis were used to study the in vivo mutagenic activity of ribavirin on bone marrow cells of Swiss albino mice. To determine the incidence of micronuclei, mice were injected i.p. twice, at an interval of 24 h. with the drug at doses of 20, 100 and 200 mg/kg. Animals were killed 6 h after the second dose and bone marrow was examined for the presence of micronuclei in developing erythrocytes. Ribavirin significantly (P less than 0.05) induced micronuclei in polychromatic erythrocytes at all doses. A study was conducted to investigate the cytogenetic effect of the drug on mitotic chromosomes. Ribavirin at 200 mg/kg/day was administered to mice for 3 and 5 days. Repeated treatment with the high dose of ribavirin produced a highly significant (P less than 0.02) increase in abnormal metaphase spreads. The results indicate that ribavirin is mutagenic to bone marrow cells of mice as evaluated by the micronucleus test and by chromosome analysis.     

The influence of intracysternal insulin administration on the rat temporal behaviour dynamics

Rat behaviour in the open field and elevated plus-maze was analyzed in rats after intracysternal administration of 2.5, 25, 50 and 200 ng of insulin in 45 min, 24 hrs and on the 9th day after single injection. Dose-dependent changes in 45 min occurred in both behavioural tests: insulin in low doses (2.5 and 25 ng) increased probability of locomotion and investigative activity in open field, while insulin in high doses (50 and 200 ng) did not alter locomotor activity and showed tendency to weakening of the investigative behavior (especially in the dose of 50 ng). Tendency was found in 24 hrs to increase probability of investigative behavior in open field after injection of 25 ng of insulin, although on the 9th day after insulin administration this behaviour increased in all experimental groups for all used doses. Insulin in the doses 2.5 and 200 ng decreased anxiety in elevated plus-maze in 45 min during the first five min; the doses 2.5 and 25 ng at the second five min exerted the same effect. In 24 hrs, the anxiety level increased for the doses 50 and 200 ng, and there was a tendency for an increase in the doses 2.5 and 25 ng; anxiety was decreased on the 9th day for all used doses of insulin. Thus, single insulin administration induced weakness of non-associative memory in open field on the day 2 and day 9 as well as increase of anxiety level on the day 2 and decrease of anxiety level on the day 9 in elevated plus-maze.     

Laetispicine, an amide alkaloid from Piper laetispicum, presents antidepressant and antinociceptive effects in mice

In the present work, we studied the effect of laetispicine, an amide alkaloid isolated from the stems of Piper laetispicum (Piperaceae), in forced swimming, open field, acetic acid writhing and formalin tests in KM mice to assess antidepressant and antinociceptive effects. A significant and dose-dependent decrease in the immobility time, as evaluated by the forced swimming test, was observed after laetispicine administration (38.18, 39.79, 58.77 and 67.28% decreased at the doses of 5, 10, 20, 40 mg/kg, respectively), suggesting an antidepressant effect. Furthermore, in the open field test, laetispicine at the given doses did not alter the number of crossings and rearing, as compared to controls. Results from writhing and formalin tests showed that laetispicine reduced the number of writhing in mice in a dose-dependent manner, attenuated the licking and spiting time of the injected paw in the first phase of formalin test. The antinociceptive effect of laetispicine was not affected by pre-treatment (i.p.) with naloxone (2 mg/kg). In conclusion, we showed that laetispicine possessed significant antidepressant and antinociceptive properties, making this drug potentially useful in depression and pain.     

环磷酰胺诱导小鼠血小板减少症模型的建立(英文）

比较由环磷酰胺两种不同给药方式诱导小鼠血小板减少症模型的效果,并对效果较稳定的一种给药方式进行最佳造模剂量摸索,以期确定一个造模效果较好,毒副作用较低,利于观察治疗药物疗效的血小板减少症模型。模型A组,第1天尾静脉注射环磷酰胺200 mg/kg,然后连续6 d,每天1次以维持剂量30 mg/kg腹腔注射环磷酰胺。模型B组,按150 mg/kg皮下注射环磷酰胺,每天1次,连续3 d。结果显示模型B组造模效果较好,故以模型B组给药方法进行剂量摸索实验。由第7天的血小板计数可知环磷酰胺低（100 mg/kg）、中（120 mg/kg）、高（140 mg/kg）剂量均可引起血小板减少症,而低剂量组与其他组比较有高效低毒的特点,更有利于观察治疗药物的作用,可用于具有升血小板作用药物的药效学研究     

Exposure to Strong Static Magnetic Fields Induces Hypoactivity in Weaning Mice

We studied the effects of a prolongued exposure to a strong (1.0 Tesla) static and uniform magnetic field upon the open field behaviour and body weight of weaning mice. We observed a marked reduction in the exploratory activity of mice exposed to the field relative to that of control animals kept in similar surroundings, and handled in the same way as the exposed mice. One week of continuous exposure to a 1.0 T field significantly reduces peripheral square entries (p<0.01) as well as rearings (p<0.05), but has no effect on body weight. Our findings agree with the suggestion that a strong magnetic field may act as stressing agent.