Behavior of male and female mice submitted to action of <Emphasis Type="Italic">p</Emphasis>-chlorophenylalanine in prenatal ontogenesis

Effect of serotonin (5-HT) deficit produced by administration of p-chlorophenylalanine at a dose of 400 mg/kg to pregnant female mice at the 8th day of gestation on the subsequent behavior of their offspring (hybrids F1(C57BL/CBA)) was studied. The 5-HT deficit in prenatal ontogenesis leads to the following behavioral changes: (1) females and males of the experimental group have a higher level of the explorative activity in the “open field” than control animals; (2) in females of the experimental group at the age of 90 days, unlike control females and males of experimental and control groups, the explorative activity is extinguished at the threefold testing in the “open field”; (3) females of the experimental group have a decreased level of anxiety in tests “elevated plus-maze” and the “dark-light” chamber. Males of the experimental group, on the contrary, have an elevated level of anxiety. The obtained data show that the 5-HT deficit at the prenatal period affects various aspects of behavior. The degree of the changes produced by the prenatal 5-HT deficit can have different manifestations depending on sex of the animals.     

Effects of prenatal disturbance in the brain testosterone metabolism on anxiety level and behavior of rats in a novel environment

The effects of maternal administration of the aromatase inhibitor 1,4,6-androstatrien-3,17-dione (ATD) during the last week of gestation on formation of behavior in a novel environment were studied in male and female offspring. The "open field" and the elevated plus-maze tests were used. The results showed that there were a significant elevation of the anxiety level and emotionality in ATD-treated 30-day-old female rats, whereas at the age of 90 days, the elevation of these behavioral parameters was observed both in males and females. There was no a sexual dimorphism in behavioral response to a novel environment such as locomotor activity, time of immobilization, total duration of grooming reaction, and anxiety level between adult control male and treated female rats. These data suggest that prenatal inhibition of the brain testosterone metabolism alters the formation of sexual dimorphism of the anxiety and behavioral response to a novel environment in adulthood.     

Effects of 5-HT1A receptor agonist and antagonist on anxiety in intact and ovariectomized female rats

The purpose of this work was to study the role of 5-HT1A receptors on the level of anxiety in adult intact and ovariectomized (OVX) female rats. The influence of chronic administration of 5-HT1A receptor agonist 8-OH-DPAT (0.05 mg/kg, s.c.) and 5-HT1A receptor antagonist NAN-190 (0.1 mg/kg, i.p.) given for 14 days alone or in combination with 17beta-estradiol (0.5 microg i.m./rat/day) was studied on behavior in the elevated plus maze. In intact females administration of NAN-190 resulted in significant increase in the number of enterings and the time spent on the open arms in every phase of the estrous cycle, however, 8-OH-DPAT failed to modify these parameters. In OVX females 8-OH-DPAT alone or in combination with 17beta-estradiol significantly increased the number of enterings and time spent on the open arms. On the contrary, NAN-190 alone or in combination with 17beta-estradiol in OVX females failed to evoke behavioral changes in the elevated plus maze. Thus, the 5-HT1A receptor antagonist NAN-190 induced anxiolytic effect in intact female rats, while 5-HT1A receptor agonist 8-OH-DPAT produced an anxiolytic profile on OVX rats. Results of this work specify the involvement of 5-HT1A receptors in behavioral mechanisms of anxiety in OVX female rats.     

Open field behavior and habituation in rats irradiated on the head with gamma-rays

The goal of this work was to establish the effects of irradiation of the head with gamma-rays on selected forms of innate behavior, as well as on the habituation process to new environment in the open field test in rats. During a 5-day control period behavioral parameters reflecting motoric and explorative activities, as well as anxiety (6 parameters in total) were followed daily in 20 male Sprague-Dawley rats in an open field. Fourteen animals were repeatedly tested after irradiation of the head with a single dose of 10 Gy of gamma-rays. The results showed statistically significant depression of motoric and explorative activities during the first 3 days after irradiation in comparison with the control period. After irradiation the level of anxiety was elevated. Habituation to a new environment was observed in non-irradiated, but not in irradiated animals. These results suggest that the applied dose of ionizing radiation influenced the brain centers involved in control of innate behavioral functions connected with response to a new environment in rats.     

Testosterone enhancement during pregnancy influences the 2D:4D ratio and open field motor activity of rat siblings in adulthood

In humans, the relationship between the prenatal testosterone exposure and the ratio of the second and the fourth digits (2D:4D) has been extensively studied. Surprisingly, data on this relationship have thus far been lacking in experimental animals such as rats. We studied the effect of maternal testosterone enhancement during pregnancy on the digit ratio and open field activity of adult progeny in Wistar rats. Elevated levels of maternal testosterone resulted in lower 2D:4D ratios and an elongated 4D on the left and right forepaws in both males and females. We found no sex difference in 2D:4D in control animals. In the open field test, control females were more active than control males and testosterone females, while the activity of testosterone females did not differ from that of control males. We found a positive correlation between motor activity and the right forepaw 2D:4D ratio of control males and females. Prenatal exposure to testosterone resulted in the disappearance of this correlation in both males and females. Our results show that elevated levels of testosterone during the prenatal period can influence forepaw 4D length, 2D:4D ratio, and open field motor activity of rats, and that these variables are positively correlated. Thus, this approach represents a noninvasive and robust method for evaluating the effects of prenatal testosterone enhancement on anatomical and physiological parameters.     

The effects of 5-HT1B characterizing agents in the mouse elevated plus-maze

Although the serotonergic system has been implicated in the modulation of anxiety states, the specific receptor subtypes that mediate these states require clarification. The effects of drugs that act preferentially at 5-HT1B receptors were evaluated on the behavior elicited in the elevated plus-maze, an animal model of anxiety. Variations in the intensity of light affected mouse behavior in the plus-maze; lower light intensity increased the entries to and time spent on the open arm in a manner similar to that seen with stress-attenuating circumstances. Opposite effects were observed in high light-intensity, similar to effects seen under elevated stress conditions. Chlordiazepoxide produced increased entries and time spent on the open arm, whereas pentylenetetrazol (PTZ) produced opposite effects. The preferential 5-HT1B agents TFMPP and mCPP exhibited a profile similar to PTZ. The effects of TFMPP in the plus-maze were reversed by chlordiazepoxide, but not by the benzodiazepine receptor antagonist flumazenil, which suggests that this effect is not directly mediated by benzodiazepine receptors. The decreased entries and time spent on the open arm of the maze following TFMPP or mCPP administration was possibly mediated by an antagonistic action at 5-HT1B receptors, since this effect was reversed by the selective 5-HT1B agonist CGS 12066B. The present study further demonstrates the utility of mouse behavior in the elevated plus-maze as a model for identifying anxio-modulatory substances.     

Consequences of the prenatal depletion of serotonin and stress on nociceptive sensitivity in rats

The long-term effects of serotonin (5-HT) synthesis alteration and of restraint stress experienced by pregnant Wistar rats on pain sensitivity (evaluated by the indices of the biphasic behavioral response in the formalin test) were studied in their 90-day-old offspring. Prenatal 5-HT depletion decreased pain sensitivity in one third of the rats and failed to change it in the rest of the rast. In these later, however, an obvious tendency for an increase of interphase duration in females and its decrease in males were revealed that indicates changing of the activity of the descending serotoninergic system modulating nociceptive signals at the level of the spinal dorsal horns. Prenatal stress decreased pain sensitivity in 50% of the rats with prenatal deficiency of 5-HT but increased it in the rest of the animals. Increase of pain sensitivity also occurred in the control rats but to a lesser extent (significantly in flexing + shaking behavior during the second phase) compared to the animals with prenatal 5-HT depletion. In the latter, sex differences were found in effects of prenatal stress on pain sensitivity. The present data point an important role of 5-HT in: 1) embryonic development of tonic nociceptive system which is modulated in the CNS by mechanisms differing from those of acute pain; 2) mediation of the prenatal stress influence on pain sensitivity in the formalin test in adult rats.     

Prenatal Effect of Fluoxetine on Nociceptive System Reactivity and Psychoemotional Behavior of Young Female and Male Rats

Reactivity of the nociceptive system, psychoemotional behavior and cognitive abilities in female and male rats born to mothers that were exposed to chronic injection of fluoxetine, a serotonin reuptake inhibitor, on days 9–20 of pregnancy were studied in a battery of behavioral tests during the prepubertal period. It was found that chronic injection of physiological saline to pregnant females evoked enhanced nociceptive responses in their offspring of both sexes while fluoxetine injection neutralized the effects of such an invasive intervention, demonstrating thereby the antinociceptive effect of this agent. Negative effects of maternal fluoxetine included a weight loss in the neonate offspring of both sexes and 25-day-old males, as well as the increased anxiety level in females only as detected in the elevated plus maze test. Fluoxetine had no effect on the level of depressive-like behavior in the forced swim test in rats of both sexes. The positive prenatal effect of fluoxetine manifested itself in males as an improved spatial learning ability in the Morris water maze; the anti-nociceptive effect of chronic fluoxetine injection, as compared to the pro-nociceptive effect of chronic saline injection, can also be considered as a positive effect of fluoxetine. Sex differences in the prenatal effect of fluoxetine were revealed in the anxiety level with more anxiety behavior in females.     

Effects of sex factors and hemispheric localization on the involvement of serotonin from the frontal cortex, striatum, and nucleus accumbens into the processing of novel and repeatedly presented information in rats

The effects of novel or relevant (a single exposure to experimental chamber) and irrelevant (20 exposures to experimental chamber) stimuli on the levels of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the frontal cortex, striatum, and nucleus accumbens in the left and right hemispheres were studied in male and female rats. It was found that 5-HT and 5-HIAA contents in the frontal cortex changed in response to neither relevant nor irrelevant stimuli. However, there were hemispheric difference in 5-HT and 5-HIAA in the frontal cortex of intact animals. The level of 5-HT in males and the level of 5-HIAA in females were higher in the left frontal cortex. In females, the level of 5-HIAA in the left striatum decreased in response to the novel stimulus. Sex differences in: a) 5-HT metabolism (increase in the level of 5-HIAA in males and increase in 5-HT in females) and b) lateralization (the striatal 5-HT metabolism in males changed bilaterally and only in the left hemisphere in females) were observed in reactions to irrelevant stimuli. Both in male and female rats, serotonin content in the nucleus accumbens changed only in response to the irrelevant stimuli. The 5-HT level increased in the left and right hemispheres independently of sex, but hemispheric difference was revealed only in females, in which the serotonin level was higher in the left nucleus accumbens. It is concluded that serotonergic neurotransmitter mechanisms are involved in hemispheric and sex differences in selective attention.     

Antinociceptive properties of the 5-HT3 receptor antagonist in the model of inflammatory pain in rats of different age with prenatal deficit of serotonine and under stress

The role of peripheral 5-HT3 receptors in the nociceptive behavioral response and the effect of the 5-HT3 antagonist ondansetron on indices of acute and tonic pain were investigated in the formalin test in 25- and 90-day-old Wistar male rats. The experimental rats were prenatally exposed to 5-HT depletion (a single injection ofparachlorophenilalanine 400 mg/kg/2 ml, i. p.; ICN, USA to the dams on day 9 of pregnancy) and to stress (dams immobilization during the last week of pregnancy). Antinociceptive effects of ondansetron in the rats with both prenatal 5-HT deficiency and stress (experimental rats) and prenatal injection of saline solution and stress (control rats) were more obvious in the younger animals. Prenatal 5-HT deficiency attenuated the antinociceptive effect of ondansetron in licking patterns in the younder age group in acute pain, and in adults--in tonic pain. Thus, the data obtained in the rats with prenatal 5-HT deficiency and stress indicate involvement of 5-HT3 receptors in mediation of prolonged pain in the formalin test, and antinociceptive effect of ondansetron which is attenuated in animals with prenatal 5-HT deficiency and specifically depends on rat's age.     

Prenatal stress and maternal behavior in intact virgin rats: response latencies are decreased in males and increased in females

The repeated findings that levels of various male-typical behaviors (e.g., copulatory behavior and intermale aggression) are reduced in prenatally stressed (P-S) males, coupled with reports of effects on female physiology and behavior, prompted us to examine the maternal behaviors of P-S animals toward young. Sprague-Dawley female rats were timed-mated (+ sperm = Day 1). From Gestation Days 15 to 22 experimental females were subjected to heat and restraint stress. Control females remained undisturbed throughout pregnancy. The offspring, as adults, were assessed for maternal behavior. P-S males exhibited a significantly shorter latency (in days) to show full maternal behavior (FMB) than Control males, median = 5.0 vs 8.0, respectively. P-S females, on the other hand, exhibited a significantly longer latency than Control females to show FMB (7.0 vs 3.0, respectively). as well as longer latencies to retrieve one, two, or three pups, to begin to crouch over pups, and to build nests in response to young. Sex differences were apparent between Control males and Control females (females were more responsive to young). In contrast, P-S males and Control females exhibited similar latencies to show components of FMB (3-5 days), as did P-S females and Control males (7-9 days). These data demonstrate, therefore, that prenatal stress eliminates the sex difference normally observed in pup-induced maternal behavior. Moreover, the data suggest that prenatal stress renders the male's responsiveness to young more "female-like," while conversely rendering the response of the female more "male-like."     

孕期低氧应激对子代雄性大鼠性行为的影响

目的:研究孕期低氧应激对子代雄性大鼠的繁殖行为及相关激素分泌的影响。方法:实验将配对获得的怀孕第14天的母鼠随机分为3组:对照组(Control)、3300m模拟高原低氧应激组和5000m模拟高原低氧应激组,实验组母鼠放入低氧舱中进行持续7天的模拟低氧应激处理,对照组在实验条件下常规饲养。结果:孕期经低氧应激子代雄性性成熟个体具有与雌性个体交配的能力,但是行为能力有不同程度的下降。同时,应激组个体肛阴距变短,血浆睾酮水平下降而皮质酮水平显著升高,而3组动物睾酮、附睾以及肾上腺指数间无显著差异。结论:出生前受到低氧应激对子代雄性个体的性行为能力产生持久的抑制影响。     

大鼠产前母体冷应激对子代自发、探索及焦虑行为的影响*

目的: 研究产前冷应激对妊娠大鼠子代行为及情绪的影响。方法: 将6只SPF级Wister妊娠母鼠,随机分为常温对照组和冷应激组,每组3只。常温对照组妊娠母鼠在(22±2)℃的环境中饲养,冷应激组妊娠母鼠在产前7 d置于人工智能气候室(4±0.1)℃中饲养,待产下幼鼠以后,分为常温对照组公鼠(MR,22只),常温对照组母鼠(FR,15只),冷应激组公鼠(MC,15只),冷应激组母鼠(FC,15只)四组,在子代第四周龄时进行旷场实验、高架十字迷宫实验。结果: 在旷场实验中,常温对照组公鼠、母鼠与冷应激组公鼠、母鼠的自发活动、探索行为之间无明显差异(P＞0.05)。在高架十字迷宫实验中,冷应激组公鼠、母鼠的开臂滞留时间、开臂进入次数及路程等总体上显著高于常温对照组公鼠、母鼠(P＜0.05)。结论: 产前母体冷应激对子代自发活动、探索行为及活跃程度无显著影响,但子代出现明显的焦虑行为减少的异常行为。     

Anxiety and fear behaviors in adult male and female C57BL/6 mice are modulated by maternal separation

This study investigated the effects of maternal separation in C57BL/6 male and female mice during infancy on later adult fear and anxiety behaviors. Additionally, we observed the maternal behavior of the dams to examine aspects of maternal care that may be modulated by daily bouts of separation. In males, mice that experienced maternal separation during the neonatal period displayed significantly higher levels of anxiety and fear behavior, as measured by the open field test and elevated plus maze, compared to control, standard facility reared males. In females, however, maternal separation reduced anxiety and fear behavior in the open field test, but only when the females were in the diestrous phase of their estrous cycle. The 30-min daily observation of the dams revealed that the separation did not significantly alter the frequency of the maternal care provided by the dam at the time point measured. These results indicate that the emotionality of adult male and female mice can be modulated by maternal separation. However, this effect is dependent on the sex of the offspring and the phase of the estrous cycle of the female.     

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.     

Gender-Specific Features of Behavior and Lipid Spectrum in Rats at a Remote Period after Exposure to Vibrational Noise

Changes in rat behavior and blood lipid spectrum were detected 3 weeks after exposure of animals to vibrational (construction) noise. Males demonstrated anxious, simplified or agitated behaviors, while females–anxious or depression-like behaviors. Most evident changes in the lipid spectrum were observed in males with simplified and females with depression-like behaviors. In anxious behavior, the high-density lipoprotein level was elevated in males and reduced in females versus control.     

Gestational exposure to bisphenol A and cross-fostering affect behaviors in juvenile mice

Bisphenol-A (BPA) is a component of polycarbonate resins, and, lately, concern has been raised about its potential negative effects on human health. BPA is an estrogen analog and, in addition, it can act as a DNA hypomethylator. We examined the effects of gestational exposure to BPA on several behaviors in C57BL/6J mice. Because BPA affects maternal care, which, may have long-lasting effects on offspring behavior, we tested mice raised by either biological or fostered dams. Both diet and dam affected behavior in juvenile mice in a social novelty task and the elevated plus maze (EPM). In a social novelty task, the amount of time spent interacting with an adult male was affected by sex and gestational diet, but only in juveniles raised by a foster dam. Control females spent less time sniffing a novel adult than did control males or females exposed to BPA during gestation. In the EPM, juveniles reared by foster dams and exposed to BPA during gestation spent less time in the distal half of the open arm as compared with juveniles gestated on a control diet. Adult offspring raised by their biological dams showed the same response pattern; gestational BPA increased anxiety as compared with control diet. Our results show that prenatal BPA exposure affects social behavior and anxiety in the EPM. Moreover, some facet(s) of the infant–maternal interaction may modify these effects.     

Social and hormonal influences on behavior of adult male, female, and pseudohermaphroditic rhesus monkeys

We previously demonstrated that in a simple pair test situation the expression of adult male sexual behavior by rhesus monkeys depends on both prenatal (organizational) and adult (activational) androgen exposure. In the present study we used a more complex social situation (trio tests) to evaluate the behavior of males, females, and female pseudohermaphrodites. In these trio tests, the experimental subjects were tested with two estrogenized stimulus females simultaneously. Sex differences in behavior were made apparent by this complex testing situation that could not have emerged in the pair test. Gonadectomized males and female pseudohermaphrodites, but not ovariectomized females that were concurrently receiving TP, exhibited increased male sexual behavior in trio tests compared to pair tests. In trio tests, the males and pseudohermaphrodites showed evidence of partner preference by interacting almost exclusively with one of the two stimulus females. These "preferred females" in turn were responsible for the majority of the proceptive behavior exhibited in these tests. Ovariectomized females rarely displayed male sexual behavior in either test situation. These results further support the hypothesis that prenatal androgen exposure predisposes monkeys to exhibit masculine behavior traits when they reach adulthood and are exposed to the activational influences of androgens.     

Effect of prenatal hypobaric hypoxia on activity of the rat brain phosphoinositide system

Activity of the phosphoinositide system of intracellular signalization was studied in offspring of rats exposed to severe hypobaric hypoxia at the 14–16th (group 1) or the 18–20th day (group 2) of prenatal hypoxia. At the age of 15 days, in animals of both experimental groups the basal level of triphosphoinositides in the brain cortex was shown to be elevated as compared with control. In the group 1, this parameter also remains elevated in adult animals. Application of glutamate produces a more pronounced increase of the inositephosphates in brain slices of the 15-day old rats of the group 1 than in slices of animals of the control group. In the 15-day old rats of the group 2, as compared with control, the phosphoinositide response to glutamate application was reduced. No changes in the inositephosphate levels were revealed after application of glutamate upon slices of adult (the 90-day old) control animals and of adult rats of the group 2. In slices of adult rats of the group 1, on the contrary, the glutamate application produced an increase of the inositephosphate content. The obtained data indicate essential changes of the phosphoinositide metabolism in the brain of rats exposed to action of hypoxia at the period of prenatal development. The character and the severity of these changes depend on the period of development when action of hypoxia occurs.