Maternal methyl-containing dietary supplementation alters the ability to learn in adult rats in swimming Morris test

Maternal choline diet influences the spatial learning processes. In this work, the learning ability of adult progeny of mothers who had received methyl diet enriched with choline and betain during pregnancy and lactation was studied in Morris test. The introduction of the diet to pregnant rats resulted in an increase in the time of search for invisible platform and time of swimming near the pool walls in offsprings, which meant a worsening of their learning ability. It was also found that change in platform searching strategy was not associated with an increase in anxiety of male rats. Possible involvement of maternal methyl diet in the change of expression of genes which control development of the nervous system is discussed.     

Effects of prenatal irradiation on behaviour and hippocampal neurogenesis in adult rats

Prenatal irradiation is known to have aversive effects on the brain development, manifested in changes in some behavioural parameters in adult individuals. The aim of our work was to assess the effect of prenatal irradiation on different forms of behaviour and on hippocampal neurogenesis in rats. Pregnant female rats were irradiated with a dose of 1 Gy of gamma rays on the 16th day of gravidity. The progeny of irradiated and control animals aged 3 months were tested in Morris water maze (MWM), open field (OF) and in elevated plus maze test (PM). The prenatal irradiation negatively influenced the short-term spatial memory in MWM in female rats, although the long-term memory was not impaired. A statistically significant increase of basic locomotor activity in OF was observed in irradiated rats. The comfort behaviour was not altered. The results of PM showed an increase of anxiety in irradiated females. The level of hippocampal neurogenesis, assessed as the number of cells labelled with 5-bromo-2-deoxyuridine in the area of gyrus dentatus, was not statistically different in irradiated rats. Our results indicate, that prenatal irradiation with a low dose of gamma-rays can affect some innate and learned forms of behaviour in adult rats. We did not confirm a relation of behavioural changes to the changes of hippocampal neurogenesis.     

Effects of leptin administration on lactational infertility in food-restricted rats depend on milk delivery

Leptin administration has been shown to prevent the disruptive effects of acute food deprivation on reproductive function in cycling females and lactating females. We examined the ability of intracerebroventricular leptin administration to ameliorate the effects of food restriction for the first 2 wk postpartum on length of lactational infertility. Leptin administration did not reduce the effects of food restriction on reproductive function at either time period (days 8-15 and 15-22 postpartum) or dose (1 and 10 microg/day) administered. Because of the sharp contrast between these results and the ability of leptin to offset the effects of acute food deprivation in lactating rats, the remaining studies investigated the possible causes of this difference. Both central and peripheral leptin administration eliminated food deprivation-induced prolongation of lactational infertility, suggesting that neither route of administration nor dose was a factor. However, we noticed that, whereas chronically food-restricted females continue to deliver milk to their young, acutely food-deprived females do not. To test the hypothesis that the continued energetic drain of milk production and delivery might prevent the ability of exogenous leptin administration to eliminate the effects of undernutrition, leptin was administered to food-restricted, lactating rats prevented from delivering milk. In this situation intracerebroventricular leptin treatment completely eliminated the effects of food restriction on lactational infertility, suggesting that leptin contributes to the maintenance of reproductive function via two pathways: direct binding in the central nervous system and through increasing the availability of oxidizable metabolic fuels.     

强制运动促进成年大鼠海马齿状回神经发生并提高学习能力

为了探讨强制运动对成年大鼠海马齿状回（dentate gyrus,DG）神经发生的影响,强制大鼠在马达驱动的转轮中跑步,用5-溴-2-脱氧尿苷（5-bromo-2-deoxyuridine,BrdU）标记增殖细胞,巢蛋白（neuroepthelial stem cell protein,nestin）标记神经干细胞／前体细胞,然后用免疫细胞化学技术检测大鼠DG中BrdU及nestin阳性细胞。为了解强制运动后DG增殖细胞的功能意义,采用Y-迷宫检测大鼠的学习能力。结果表明,强制运动组DG中BrdU及nestin阳性细胞数均日月显多于对照组（P〈0．05）：强制运动对DG神经发生的效应有强度依赖性。Y-迷宫检测结果显示,强制运动能明显改善大鼠的学习能力。结果提示,在转轮中进行强制跑步能促进成年火鼠DG的神经发生,并改善学习能力。     

Ontogenetic formation of the ability for endogenous account of time and its dependence upon the anxiety level in rats

Rats' ability for endogenous account of short time intervals progresses along with maturation. In 3- and 6-month old animals, it parabolically depends upon the level of anxiety: there is an average optimum level of anxiety needed for precise and effective account of time. Deviations from this level decrease the biochronometrical ability. In addition, a time perception dependence on locomotive sphere and the state of sympathetic adrenal system's peripheral part, was revealed.     

Effects of pyramidotomy on instrumental reflexes in rats depend on the duration of its execution

The effects of unilateral transection of bulbar pyramids on instrumental conditioned reflexes in rats were shown to be in direct relationship with the time of its execution. In rats with stable conditioned reflexes, pyramidotomy impaired conditioned performance, on the average, for 3.9 days. However, preliminary transection of the pyramid delayed operant conditioning and its stabilization, on the average, by 16.5 day. The findings are discussed in terms of the mechanisms of switching over descending influences of the cortico-spinal and cortico-rubrospinal systems.     

Effects of testosterone on spatial learning and memory in adult male rats

A male advantage over females for spatial tasks has been well documented in both humans and rodents, but it remains unclear how the activational effects of testosterone influence spatial ability in males. In a series of experiments, we tested how injections of testosterone influenced the spatial working and reference memory of castrated male rats. In the eight-arm radial maze, testosterone injections (0.500 mg/rat) reduced the number of working memory errors during the early blocks of testing but had no effect on the number of reference memory errors relative to the castrated control group. In a reference memory version of the Morris water maze, injections of a wide range of testosterone doses (0.0625-1.000 mg/rat) reduced path lengths to the hidden platform, indicative of improved spatial learning. This improved learning was independent of testosterone dose, with all treatment groups showing better performance than the castrated control males. Furthermore, this effect was only observed when rats were given testosterone injections starting 7 days prior to water maze testing and not when injections were given only on the testing days. We also observed that certain doses of testosterone (0.250 and 1.000 mg/rat) increased perseverative behavior in a reversal-learning task. Finally, testosterone did not have a clear effect on spatial working memory in the Morris water maze, although intermediate doses seemed to optimize performance. Overall, the results indicate that testosterone can have positive activational effects on spatial learning and memory, but the duration of testosterone replacement and the nature of the spatial task modify these effects.     

胎次、性别对成年小鼠海马齿状回神经发生及学习记忆的影响

目的探讨胎次、性别是否对成年小鼠海马齿状回神经发生及学习记忆产生影响。方法运用Morris水迷宫系统检测第1～3胎成年小鼠的学习记忆能力,腹腔注射BrdU,标记神经干细胞,检测不同胎次、性别小鼠海马齿状回中的神经发生的差异。结果 （1）在同性别、不同胎次成年小鼠间,第2胎的学习记忆能力（LMA）均显著地高于第1、3胎的,其影响规律为LMA2〉LMA1〉LMA3,且P〈0.05;在同胎次、不同性别成年小鼠间,雌性小鼠的LMA均高于雄性小鼠的,但其差异无显著性（P〉0.05）。（2）在同性别、不同胎次成年小鼠间,第2胎海马DG新生神经细胞的数量（N）均高于第1、3胎的,其影响规律分别为NF2〉NF3〉NF1和NM2〉NM1〉NM3,但其差异无显著性（P〉0.05）;在同胎次、不同性别成年小鼠间,雌性小鼠的N均高于雄性小鼠的,但其差异无显著性（P〉0.05）。结论胎次、性别对实验动物神经发生及学习记忆等方面产生的影响是肯定的。因此,在使用实验动物时,应予以充分考虑,尽量使用胎次、性别相同的。     

Effects of ovariectomy and chronic estradiol administration on pituitary-thyroid axis in adult rats

The effects of ovariectomy (Ovx) and of ovariectomy followed by chronic estradiol dipropionate administration (Ovx EDP) on the structure and function of the pituitary-thyroid axis were examined in the rat. Pituitary TSH cells and thyroid tissue were histologically, immunohistochemically and stereologically investigated. Serum TSH and T(4) levels were determined by RIA. Ovx did not affect pituitary weight, but subsequent treatment with EDP led to its more than two-fold increase (p<0.05). After ovariectomy, the cellular volume of pituitary TSH-immunoreactive cells increased by 28%, p<0.05 compared to sham-operated animals (SO). Treatment of Ovx rats with EDP partially reversed this change. However, the relative volume density of thyrotrophs decreased in comparison to the Ovx and SO groups (by 18% and 23%, p<0.05, respectively). No statistically significant differences in serum TSH levels were observed between the experimental groups. In thyroid tissue both peripheral and central follicles responded to Ovx and EDP treatments. Compared to SO rats, the relative volume densities of the follicles and colloid were increased (by 14% and 30%, p<0.05, respectively) in Ovx rats. Chronic EDP treatment of Ovx rats reversed these changes to the pre-ovariectomy state. Hyperplasia of thyroid follicular cells and a significant reduction (by 21%, p<0.05) of the serum level of T(4) were detected. In conclusion, estradiol deficiency and chronic treatment affected pituitary TSH cells and thyroid tissue. The sum effect of Ovx on the pituitary-thyroid axis was slightly stimulatory. Subsequent EDP treatment decreased thyroid functioning but at the same time preserved serum TSH at the control level.     

Effects of cobalt on postnatal development and late gestation in rats upon oral administration

Four groups of pregnant Wistar rats, each of which consisted of 15 animals were administered 0, 12, 14 and 48 mg/kg/day of cobalt (II) chloride from the 14th day of gestation through 21 days of lactation. The offspring were observed for mortality, body weight, body and tail length and general symptomatology after 1, 4 and 21 days of nursing. The number of litters was higher for the control group. The survival ratios were also higher for the control group. Besides, a dose-dependent delay in the growth of the living young could be observed. No significant differences in organ weights in the animals killed 21 days after birth were observed. The blood parameters analysed did not show differences between the treated and control pups. Cobalt produced toxic effects on the mothers, affecting the late gestation as well as the postnatal development of the pups.     

Effects of pyridostigmine on ability of rats to work in the heat

Adult, male rats (300-325 g) were treated with pyridostigmine bromide (n = 22) or saline (n = 22) to quantitate the effects of cholinesterase inhibition (64%) on the ability to work (9.14 m/min, level treadmill) in the heat (35 degrees C). Pyridostigmine-treated rats had a mean endurance of 23 min, whereas saline-treated animals ran for nearly 35 min (P less than 0.001). Rates of rectal and skin temperature increments were significantly higher (P less than 0.001) in pyridostigmine-treated rats as were water losses (P less than 0.001). Exercise in the heat to hyperthermic exhaustion effected anticipated increments in circulating urea nitrogen, creatinine, lactate dehydrogenase, and potassium levels, whereas pyridostigmine pretreatment had additive effects on lactate and creatine kinase concentrations. Additionally, pyridostigmine elicited a significant (P less than 0.01) hyperglycemia before exercise, an effect noted also with other organophosphate simulants. We concluded that pyridostigmine-induced cholinesterase inhibition had a variety of debilitating effects during work in the heat.     

Effects of central administration of beta-amyloid peptide (25-35): pathomorphological changes in the hippocampus and impairments of spatial memory

A possible relationship between the amnesia induced by central administration of beta-amyloid (25-35) [Abeta(25-35)] and neurodegeneration in the hippocampus was studied. Male Wistar rats received a single intracerebroventricular injection of Abeta(25-35) at a dose of 15 nmol. One month after the administration, animals were trained in an eight-arm radial maze. After the training, a histopathological investigation of the hippocampus was carried out using brain slices stained with hematoxylin/eosin. Abeta(25-35) induced impairments in reference and working memory in the eight-arm radial maze. A moderate decrease in neuronal cell number was demonstrated in the CA1, but not in the CA3 subfield of the hippocampus. The number of both reference and working errors negatively correlated with the number of neurons in hippocampal CA1. The results are the first evidence for a specific relationship between neurodegeneration in the CA1 subfield of rat hippocampus and impairments of learning and memory induced by Abeta(25-35).     

Effects of intraperitoneal administration of gabapentin on the minimum alveolar concentration of isoflurane in adult male rats

Gabapentin has been used to treat a variety of conditions in both human and veterinary medicine, including seizures, neuropathies and chronic pain. However, little information is known about the effects of gabapentin on the minimum alveolar concentration (MAC) of volatile anaesthetics. In this study, we investigated the effect of intraperitoneal administration of gabapentin on isoflurane MAC in adult male rats and hypothesized that gabapentin would decrease MAC in a dose-dependent manner. Using a standard MAC study protocol, we compared five treatment groups (G) receiving 0 (G(0)), 30 (G(30)), 100 (G(100)), 300 (G(300)) and 1000 (G(1000)) mg/kg gabapentin intraperitoneally and compared post-drug MAC values among groups and with corresponding baseline MAC values determined in each group prior to drug testing. The average baseline isoflurane MAC value was 1.45 ± 0.17%, which did not differ significantly between groups (1.47 ± 0.23% [G(30)], 1.46 ± 0.23% [G(100)], 1.48 ± 0.18% [G(300)] and 1.42 ± 0.2% [G(1000)]). In the G(300) and G(1000) groups, the isoflurane MAC value decreased significantly by 19% and 18%, respectively, from corresponding baseline values (P< 0.05, when compared with G(0)). Linear regression analysis revealed a negative correlation between blood gabapentin concentration and percent change in MAC (R(2) = 0.43; P< 0.05) but not dose. In conclusion, high-dose intraperitoneal gabapentin decreased isoflurane MAC. However, the effect was small and not dose-dependent, and is unlikely to be clinically significant.     

Effects of chronic lithium administration on brain weights, acetylcholinesterase activity and learning ability in rats

In order to test the effects of chronic lithium (Li) administration on learning and memory, 21 day old rats were subjected to different degrees of environmental stimulation (enriched condition, EC and impoverished condition, IC) with and without Li for 144 days. Li was administered with food (2.18 mEq/Kg weight/day). Average plasma Li concentration at the end of the experiment was 0.41 +/- 0.04 mu Eq/ml. Both Li treatment and the environmental condition showed an overall significant effect on the cortex/subcortex weight ratio and learning ability index, but not on AChE activity in occipital cortex. A similar pattern of brain Li distribution was observed in both EC-Li and IC-Li, with occipital cortex having the highest levels. Li tissue/protein/plasma ratio was higher in EC than in IC, in all the brain areas studied. Other organs (liver and kidney) did not show EC-IC differences in the tissue/protein/plasma Li ratio.     

Effects of vanadium on reproduction, gestation, parturition and lactation in rats upon oral administration

Sodium metavanadate was tested for its effects on fetal development, reproduction, gestation and lactation in Sprague Dawley rats. Male rats were administered NaVO3 po at doses of 0, 5, 10 and 20 mg/kg/day for sixty days before mating with females which had received the same doses from 14 days previous to mating. These females received 0, 5, 10 and 20 mg NaVO3/kg/day during the periods of gestation and lactation. No significant adverse effects could be observed on: number of corpora lutea, implantations, live and dead fetuses, and resorptions. Significant decreases were observed in the development of the pups in all the vanadium -treated groups. All the doses used produced toxic effects in the offspring.     

Effects of acute and chronic trazodone administration on serum prolactin levels in adult female rats

Trazodone was tested for its ability to elevate serum prolactin levels in mature female rats. When the drug was administered acutely to female rats at doses up to 80 mg/kg ip, it induced a clear rise in serum prolactin levels, with a minimum effective dose of 20 mg/kg; blood trazodone levels at these doses were between 1.6–2.4 μg/ml. However, trazodone could not be considered to be a potent stimulator of prolactin secretion, since the injection of haloperidol at 2 mg/kg elevated serum prolactin to values twice those seen in animals receiving the 80 mg/kg dose of trazodone. When trazodone was administered chronically in the diet for two or four weeks, at an average daily dose of 80 mg/kg, serum trazodone levels were found to be 100–200 ng/ml when measured at each stage of the estrous cycle. Serum prolactin levels in trazodone-treated animals, however, did $\text{not}$ differ from those in control rats. Moreover, drug-treated animals showed normal proestrus surges in serum prolactin. The results of these studies thus indicate that acutely, at very high doses, trazodone probably can stimulate prolactin secretion modestly in female rats. However, when consumed chronically at 80 mg/kg/day, the drug has no effects on serum prolactin levels. Therefore, if trazodone stimulates prolactin secretion by altering neurotransmission across dopamine and/or serotonin synapses in brain, it is probably not potent in these actions, at least as concerns those dopamine and serotonin neurons that influence the secretion of prolactin.