Seizure susceptibility and avoidance conditioning in adult rats treated prenatally with chlorpromazine

Offspring of female rats treated early in gestation with chlorpromazine (CPZ) were tested at 30 days of age for seizure susceptibility and at 90 days of age for shock avoidance learning. Fostering procedures permitted separation of prenatal influences from postnatal rearing influences of drug treatment. Offspring of drug-treated mothers had higher avoidance scores, higher intertrial activity levels, and greater seizure susceptibility than offspring of controls. Animals reared by previously treated mothers also had higher avoidance and greater seizure susceptibility. This postnatal effect depended on sex and was not accompanied by an overall increase in intertrial activity. Rearing by a previously drug-treated mother was also found to modify the influence of neonatal stress on adult avoidance learning.     

Effects of fostering on seizure activity in the Mongolian gerbil

The purpose of this experiment was to ascertain whether seizure propensity in Mongolian gerbils is affected by differences in behavior and/or nurturing ability of seizure-prone (SP) and nonseizure-prone (NSP) parents. Day-old SP and NSP pups were cross-fostered, while other SP pups were fostered to SP parents. Matched nonfostered littermates served as controls. The SP gerbils fostered to NSP parents exhibited delayed onset of seizure activity whereas SP gerbils fostered to SP parents did not. Neither fostered nor nonfostered NSP gerbils ever underwent seizures. This experiment establishes that some familial defect underlies seizure-proneness in gerbils, but that expression of this tendency is affected by parental behavior and/or nurturing ability.     

大鼠脑缺血对癫痫敏感性和脑内胶质原纤维酸性蛋白免疫反应的影响

本实验采用改良栓线法制备大鼠右侧大脑中动脉 (Middlecerebralartery ,MCA)缺血再灌注模型 ,腹腔注射阈下剂量 (35mg/kg·2d)戊四唑 (pentylenetetrazol,PTZ)制备慢性癫痫点燃模型。通过观察大鼠的行为 ,来检测其癫痫敏感性的改变。分别用硫堇染色、免疫细胞化学方法观察PTZ点燃脑缺血大鼠的相应脑区的神经病理学改变及脑内胶质原纤维酸性蛋白 (gliafibrillaryacidicprotein ,GFAP)免疫反应活性 (immunoreactivity,IR)的变化。结果显示 :脑缺血后大鼠癫痫敏感性明显增强 (P <0 0 5 )。右背侧海马CA1、CA3 区锥体细胞、额叶皮质神经元不同程度的脱失 (P <0 0 5 )并出现大量GFAP免疫反应阳性的星形胶质细胞 ,且细胞体积变大 ,突起变长变粗 ,免疫染色强度明显增强 (P <0 0 5 ) ,提示脑缺血大鼠癫痫敏感性增强 ,可能与海马及额叶皮质的神经元脱失及星形胶质细胞活化增生有关。     

Neuroendocrine disorders in adult rats treated prenatally with hydrocortisone acetate

We investigated the effects of hydrocortisone acetate administered to pregnant rats over the last gestational week on some neuroendocrine characteristics in adult female and male offspring. Prenatal glucocorticoid eliminated sex dimorphism of the neurons nuclei volumes in the medial preoptic area and the suprachiasmatic nuclei. There was no elevation of blood plasma corticosterone level after noradrenaline infusion into the third brain ventricle in experimental males; meanwhile, in females adrenocortical response was augmented. Male offspring exhibited a decrease of plasma corticosterone response to an acute stress (1h restraint) that was not accompanied by post-stress changes neither in the hypothalamic noradrenaline content nor hippocampal glutamate decarboxylase activity. On the contrary, moderate augmentation of adrenocortical stress reactivity and inhibitory effect of GABAergic system were found in females. It was concluded that exposure to prenatal glucocorticoid is able to alter development of the neuroendocrine systems related to reproduction and stress responses both in males and females and resulted in modification of its sex-dimorphic features in adult life.     

Superoxide dismutase activity in the brain of rats prenatally treated with lead

Cu/Zn superoxide dismutase activity in the brain of offspring of female rats treated with various concentrations of lead at various periods before and during pregnancy was reduced, which indicated disturbances of the antioxidant system. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 12, pp. 667–669, December, 1999     

Effects of the microphthalmic while gene on audiogenic seizure susceptibility in mice

Audiogenic seizure susceptibility was studied in mice segregating for the microphthalmic white gene (Mi^wh). Previous work by Deol had indicated that mice with either one or two Mi^wh alleles had severe inner ear defects. A congenic inbred strain provided mice that were identical in genetic background except for single-gene substitutions at the microphthalmia locus. The three genotypes tested were Mi^wh/Mi^wh, Mi^wh/+, and +/+. Mice were exposed to the sound stimulus once for a 1-min period between the ages of 17 and 30 days. Heterozygous Mi^wh/+ mice had more seizures and were more reactant than either type of homozygote at all ages tested. Responses were low at 17 days of age, peaked sharply by 23 days, and declined markedly by 30 days.     

1,2-Dimethylhydrazine carcinogenesis in CBA male mice prenatally treated with diethylstilbestrol.

CBA female mice, at the 17th day of pregnancy, received single intraperitoneal injection of diethylstilbestrol (DES) at the dose of 1 mg/kg body weight (b. w.). Their descentands at the age of 2 months started receiving subcutaneous injections of 1,2-dimethylhydrazine (DMH) at the dose level of 8 mg(base)/kg b. w., total 15 weekly injections. Prenatal DES treatment of male mice considerably accelerated the development and increased the incidence of DMH-induced androgen-dependent renal adenomas and, notably, renal capsule angiosarcomas (RCA). In males receiving prenatal DES (without subsequent DMH-treatment), there was a statistically significant increase of renal adenomas and 9% of RCA were observed which are exceedinly rare in untreated mice. The enhancement of androgen-dependent tumourigenesis may be considered as an indication, even though indirect, of the hyperandrogenization produced in male mice by the prenatal DES treatment.     

Hepatic glutathione mediated antioxidant system in ethanol treated rats: Decline with age.

Alcoholism is a pervasive problem. The aim of the present study was to clarify the effect of ethanol on the hepatic glutathione antioxidant system in young and elderly rats. Male albino Wistar rats of two age groups (3 months and 18 months old) were divided into two experimental groups. The first group of untreated rats served as controls (C; young n=6 and old n=6) and second group received ethanol (Et; young n=6 and old n=6) 2g of ethanol/kg b.w. for 2 months. After the completion of last treatment glutathione (GSH) and antioxidant enzymes glutathione peroxidase (GSH-Px), glutathione reductase (GR) and glutathione-S-transferase (GST) were determined. All these parameters including GST were remarkably decreased in the liver with advancing of age. The ethanol treatment decreased GSH, GSH-Px and GR, whereas, GST was increased in both age groups. The decrease of hepatic antioxidant status with ethanol and aging may be due to over production of free radicals. The changes of parameters studied were greater in the older than in the young rats. In conclusion, ethanol stress exhibited age dependent response on glutathione mediated antioxidant system in the liver.     

Prenatal maternal d-amphetamine effects on emotionality and audiogenic seizure susceptibility of rat offspring.

Dosages of 0, 5, and 10 mg/kg body weight of d-amphetamine were injected subcutaneously to gravid albino rats during Days 5-9 or Days 12-16 of gestation. Offspring were assessed for water-wading emotionality and audiogenic-seizure behaviors. No significant differences among groups were found in defecation scores from either test. The only animals to exhibit a considerable incidence of wild-running attacks or seizures were these whose mothers had received the placebo early in pregnancy. These differences are in agreement with most findings that indicate an enhancement of immunity to audiogenic seizures susceptibility as a function of prior stress. Maternal administration of d-amphetamine during pregnancy apparently can produce offspring who have less susceptibility to severe emotional responses but no protection against mild expressions of emotionality.     

Influence of culture medium on susceptibility testing with BAY n 7133 and ketoconazole.

The effect of four culture media (two complex and undefined [Sabouraud glucose and Kimmig] and two synthetic and defined [synthetic amino acid medium, fungal, and modified yeast nitrogen base]) on the activity in vitro of two newer azole compounds (BAY n 7133 and ketoconazole) was assessed with five strains each of Candida albicans, Candida parapsilosis, and Cryptococcus neoformans. Also, the nutritional adequacy of the four media was evaluated with the same 15 strains of yeastlike fungi. While the MICs of BAY n 7133 were higher in the complex media, the activity of ketoconazole was little affected. The Candida spp. grew least well and the C. neoformans grew best in yeast nitrogen base.     

Hippocampus protein profiling reveals aberration of malate dehydrogenase in chlorpromazine/clozapine treated rats

Chlorpromazine and clozapine are antipsychotic agents used to relieve symptoms of early-diagnosed schizophrenia. In this study, we used proteomics technology to screen the protein aberration in Sprague-Dawley rats treated with these two antipsychotic agents. Our goal was to identify the effects of antipsychotics on hippocampal proteins in rats. Protein expression profiles were compared in each experimental group using two-dimensional gel electrophoresis and identified using matrix-assisted laser desorption/ionisation time of flight mass spectrometry. Malate dehydrogenase, peroxiredoxin 3, vacuolar ATP synthase subunit beta and mitogen-activated protein kinase kinase 1 were found to have altered expression levels in the groups treated with antipsychotics compared with the matched controls. These findings should contribute to identifying new targets for disease preventing pharmacological agents and be beneficial for the development of more effective agents.     

Effects of early experience on the metabolism and production of corticosterone in rats.

Rats were handled for 3 min daily for 3 weeks before or after weaning or were left totally undisturbed. At 80 days of age, animals from each group were selected for corticosterone half-life determination. Adrenal tissue from thr remaining animals was incubated in vitro in the presence or absence of ACTH. Handled and unmanipulated animals did nto differ in half-life or in adrenocortical output. These data do not support the hypothesis that the reduced adrenocortical reactivity that results from manipulating animals is due to either the metabolsim of corticosterone or the response of the adrenal cortex to ACTH.     

Developmental patterns of seizure susceptibility in inbred strains of mice.

Samples of mice from each of 6 inbred strains were tested for audiogenic and electroconvulsive seizures at 5 ages (14, 21, 28, 35, and 42 days). A moderately large within-strain correlation (.67) was found, indicating that developmental patterns of susceptibility to audiogenic and electroconvulsive seizures are similar within each strain. The finding of an even larger between-strain correlation (.91) indicated that strains which are highly susceptible to audiogenic seizures are also likely to be highly susceptible to electroconvulsive seizures. In a 2nd experiment, whole brain norepinephrine and serotonin were assayed in each of 5 inbred strains at 21 and 42 days of age. Results were consistent with the hypothesis that levels of these amines are inversely related to seizure susceptibility. Mice from strains which were susceptible to seizures at 21 days of age had significantly lower levels of norepinephrine and serotonin in brain than did 42-day-old, seizure-resistant animals.