Locomotor activity changes following lipopolysaccharide treatment in mice: a multivariate assessment of behavioral tolerance

To determine the effects of repeated, acute endotoxin exposure on locomotor behavior, male laboratory mice were injected intraperitoneally with lipopolysaccharide (LPS: 50, 100 or 200 microg/kg) or saline vehicle on experimental Days 1, 4 and 7. At 2 h after each treatment, locomotor activity was assessed in a nonnovel, automated open-field apparatus (Digiscan) for 30 min. On Day 1, all horizontal and vertical activity measures were significantly reduced to near zero values by each dose of LPS. Behavioral tolerance to LPS formed rapidly, as locomotor activity of the treated groups did not differ from the control group on Days 4 or 7. In a second study, mice were given LPS (50, 100 or 150 microg/kg ip) or saline vehicle on two test days, 28 days apart. Activity was assessed, 1 h after injection, in a novel open field on the first test day and in a nonnovel open field on the second test day. Significant locomotor activity decrements were readily apparent in LPS-treated mice only in the nonnovel open field. This latter finding indicates that environmental novelty mediates, at least partially, the locomotor-reducing effects of LPS in mice.     

Behavior of streptozotocin-diabetic mice in tests of exploration, locomotion, anxiety, depression and aggression

The present study examined behavior of streptozotocin-diabetic mice in Porsolt's swim test, a putative animal model of depression, in the holeboard test of exploration and locomotor activity, in the plus maze test of anxiety, and in the resident-intruder paradigm of aggression. Two weeks after an IP injection of 200 mg/kg streptozotocin, which caused a 20% weight loss and increased fluid consumption and urination, male NIH Swiss mice were found to show lengthened duration of immobility in the swim test. One week of insulin treatment (0.1 IU/g/day) partially antagonized this change. The locomotor activity scores in the streptozotocin-treated mice were lower in the holeboard but higher in the plus maze than in the controls; therefore, the lengthened immobility was not likely to be due to a general motor impairment. No significant changes in the time spent in social interaction or aggressive behavior were found in the streptozotocin-treated mice. The results indicate that streptozotocin-treated mice show lengthened immobility in the swim test.     

The influence of nutrition on neural and behavioral development. 3. Development of some motor, particularly locomotor patterns during infancy

The locomotor development of infant rats nursed by mothers that had free access to food during lactation or were fed during that period 40% or 20% of the ad lib diet were compared. The “spontaneous” emergence or disappearance of several locomotor patterns were sampled daily in an open field situation, and the development of others was studied by inducing them in test situations. The spontaneous motor patterns included general locomotor activity, pivoting, head lifting, and standing on the hindlegs. The induced activities were hanging and moving on a suspended horizontal string, clinging to and descending on vertical ropes, climbing up on a rod, and homing in various test situations. The motor performance of the severely undernourished animals (offspring of mothers on a 20% diet) was inferior to normals in all the observations. This was manifested most commonly in reduced frequency or speed in the performance of certain acts, and in some cases in the prolonged persistence of infantile motor patterns or a delay in the appearance of more advanced patterns.     

The acute effects of 3-nitropropionic acid on the behavior and spontaneous cortical electrical activity of rats

In this study, the acute effect of 3-nitropropionic acid was investigated on open field and startle behavior of rats, and on their cortical electrical activity. Spontaneous locomotor activity, acoustic startle response, and pre-pulse inhibition of acoustic startle were measured in male Wistar rats (10 weeks old, 180-200 g body weight) after a single dose of 10 or 20 mg/kg i.p. 3-nitropropionic acid. After the behavioral tests, the rats were anaesthetized, and spontaneous cortical electrical activity was recorded. The vertical, horizontal and local open field performance showed dose-dependent deterioration in the rats treated with 3-nitropropionic acid. The number of "noise-positive" startle responses showed non-significant changes, but the inhibition by pre-pulse was significantly reduced in the high dose animals. High dose also increased the proportion of low-frequencies in the cortical activity. 3-nitropropionic acid, known primarily to act in repeated doses (e.g., in animal models of Huntington's disease) had also some clear-cut acute effects on behavioral and electrophysiological parameters of the treated rats.     

Effects of phenobarbital given to pregnant mice on behavior of mature offspring.

Mature offspring of C57BL/6J mice (Mus musculus) injected daily with phenobarbital (40 mg/kg) for the last third of pregnancy differed from saline and untreated control animals on 3 measures of behavior. Offspring of phenobarbital treated animals had higher locomotor scores than controls during an open field activity test at 75 days of age. Male offspring were also tested on a 1-trial passive avoidance task and treated animals were found to be deficient. Finally, female offspring responded less than controls on fixed ratio schedules of reinforcement. The behavioral changes suggest that offspring of mice injected with phenobarbital during pregnancy are less responsive to the stimuli in their environment which maintain behavior.     

慢性间歇性低压低氧对老年大鼠自发运动行为及黑质多巴胺能神经元的影响

目的:用慢性间歇性低压低氧(CIHH)模型,探讨CIHH对老年大鼠自发运动行为以及黑质多巴胺能神经元的影响。方法:用CIHH模型处理老年大鼠30 d,通过旷场实验检测大鼠自发运动行为的改变,通过实时定量PCR和免疫印迹检测黑质多巴胺能神经元酪氨酸羟化酶(TH)和多巴胺转运体(DAT)表达的变化。结果:老年组大鼠旷场实验中闻嗅行为、探索行为、运动行为和理毛行为与成年组相比均显著下降,CIHH处理后理毛行为没有改变,闻嗅行为、探索行为和运动行为显著改善,但没有达到成年组水平;老年组大鼠黑质多巴胺能神经元TH和DAT的表达与成年组相比均显著下降,老年CIHH组TH和DAT的表达升高,但没有达到成年组水平。结论:CIHH可改善老年大鼠闻嗅行为、探索行为和运动行为,并提高黑质多巴胺能神经元TH和DAT的表达。     

Impact of maternal morphine and saline injections on behavioral responses to a cold water stressor in adult male and female progeny

The purpose of the present study was to test the effects of maternal morphine and saline injections on chronic cold water stress responses in three groups of adult male and female rats: prenatally morphine-exposed adult progeny, prenatally saline-exposed adult progeny, and control groups. All male rats were gonadally intact, and female rats were ovariectomized (OVX) in adulthood, and half of them were injected with estradiol benzoate (EB). All animals were exposed to a cold water stressor daily for 2 weeks and tested before (baseline) and after (stress effects) the chronic cold water stressor in a swim test and an open field test. In the swim test, both adult males and OVX, EB-treated adult females born to mothers injected with morphine or saline displayed more floating behavior during the swim test than their controls, both before and after the cold water stressor. Male rats exposed to morphine or saline prenatally also spent more time struggling during the swim tests than controls, and this was further increased after the cold water stressor. In the open field test, males and OVX, EB-treated females born to morphine- or saline-injected mothers were less active and displayed fewer rearings than controls. No differences were observed in OVX females as a result of prenatal injections. Thus, the present study demonstrates that maternal injections, regardless of injection content, induce long-lasting effects on stress responsiveness in adult progeny.     

Prenatal psychological stress causes higher emotionality, depression-like behavior, and elevated activity in the hypothalamo-pituitary-adrenal axis

In humans, stressful events during pregnancy may raise the risk of psychiatric disorders in offspring, and studies with rodents have found that physical prenatal stress can cause changes in the physiology, neurobiology, and behavior of offspring. In the present study, we examined whether psychological prenatal stress with little physical stress could cause changes in the neurobiology and behavior of offspring in Sprague-Dawley rats, as physical prenatal stress did. Dams received psychological stress by observing a rat being electrically shocked behind a transparent wall in the social communication box during the last trimester of gestation but were not exposed to any physical stress. Male offspring from the dams exposed to psychological stress showed enhanced emotionality in an open field test, depression-like behavior in a forced swim test, and enhanced activity in the hypothalamo-pituitary-adrenal axis, compared with rats from untreated dams. However, the prenatally stressed rats showed intact ability to acquire context conditioning. This is the first report that psychological prenatal stress in the communication box can cause changes in the neurobiology and behavior of offspring in rodents.     

Naloxone Effects on Behavior of Inbred Mice with Different Response to Emotional Stress in Open Field Test

Effects of nonspecific opiate receptor antagonist naloxone in doses of 0.1, 0.5, 1.0, 5.0, 10.0 mg/kg on open field behavior and spontaneous motor activity were studied in male BALB/c and С57Bl/6 mice. Differently directed effects of naloxone on behavioral parameters of emotional-stress reaction in BALB/c and С57Bl/6 mice were observed. Naloxone increased motor activity in the open field test in BALB/c mice, but decreased it in С57Bl/6 mice. In the absence of stress, naloxone in the studied dose range did not affect spontaneous motor activity in С57Bl/6 mice, and significantly reduced activity in BALB/c mice in doses 0.5 and 1.0 mg/kg.     

Perinatal and chronic hypothyroidism impair behavioural development in male and female rats

A lack of thyroid hormone, i.e. hypothyroidism, during early development results in multiple morphological and functional alterations in the developing brain. In the present study, behavioural effects of perinatal and chronic hypothyroidism were assessed during development in both male and female offspring of hypothyroid rats. To induce hypothyroidism, dams and offspring were fed an iodide-poor diet and drinking water with 0.75% sodium perchlorate; dams starting 2 weeks prior to mating and pups either until the day of killing (chronic hypothyroidism) or only until weaning (perinatal hypothyroidism) to test for reversibility of the effects observed. Neuromotor competence, locomotor activity and cognitive function were monitored in the offspring until postnatal day 71 and were compared with age-matched control rats. Early neuromotor competence, as assessed in the grip test and balance beam test, was impaired by both chronic and perinatal hypothyroidism. The open field test, assessing locomotor activity, revealed hyperactive locomotor behavioural patterns in chronic hypothyroid animals only. The Morris water maze test, used to assess cognitive performance, showed that chronic hypothyroidism affected spatial memory in a negative manner. In contrast, perinatal hypothyroidism was found to impair spatial memory in female rats only. In general, the effects of chronic hypothyroidism on development were more pronounced than the effects of perinatal hypothyroidism, suggesting the early effects of hypothyroidism on functional alterations of the developing brain to be partly reversible and to depend on developmental timing of the deficiency.     

Cocaine-induced locomotor activity is enhanced by exogenous testosterone

Anabolic-androgenic steroids are synthetic derivatives of testosterone, which are increasingly abused by adolescent populations who also abuse psychoactive substances. All these compounds lead to complex behavioral syndromes and the effects of their interactions remain unclear. The main aim of the present study was to determine the influence of testosterone on the locomotor activity-promoting effect of cocaine on male mice in an open field. In the three experiments, animals received two injections: firstly, testosterone or peanut oil, and secondly, cocaine or saline solution. In Experiments 1 and 2, testosterone (or oil) and cocaine (or saline) were injected 45 and 10 min, respectively, prior to activity recording. In the first experiment, we studied the effects of testosterone (2 mg/kg) on locomotor activity induced by different doses of cocaine (2, 4, 8, 10 or 12 mg/kg). In Experiment 2, we explored the effects of supraphysiological doses of testosterone (2, 6, 10 or 14 mg/kg) on animals treated with 10 mg/kg cocaine. Finally, in the third experiment, 14 mg/kg testosterone or vehicle was administered 15, 30, 45 or 75 min before activity data collection to animals that received 10 mg/kg cocaine or saline. Testosterone itself had no effects on spontaneous locomotor activity and, as was expected, cocaine increased locomotor activity dose-dependently. Given together, testosterone enhanced the cocaine-induced hyperactivity although not dose-dependently, the highest effects being found 45 min after testosterone injection. The present study confirmed the existence of an interaction between testosterone and cocaine at the central nervous system.     

Maternal isobutyl-paraben exposure alters anxiety and passive avoidance test performance in adult male rats

Isobutyl-paraben (IBP), one of the most widely used preservatives, exhibits estrogenic activity. In this study, we analyzed the effects of maternal IBP treatment on the emotional behavior and learning performance in mature offspring. Pregnant female Sprague–Dawley rats were treated with IBP via a subcutaneous Silastic capsule. Consequently, the offspring were exposed to IBP during gestation through the placentae, and before weaning through the milk. Male and female offspring were tested for emotional behavior in an open field and in an elevated plus maze at five and six weeks old, respectively. IBP-exposed male (but not female) rats spent less time in the open arms of the elevated plus maze. At 11 weeks old, all females were gonadectomized and treated chronically with 17β-estradiol or cholesterol by Silastic capsules; all males were kept intact. They were tested for learning performance in a passive avoidance test and a Morris water maze. IBP exposure impaired the performance of males in the passive avoidance test. These findings suggest that male rats are more affected by early exposure to IBP than female rats. IBP affects their adult behavior including anxiety and learning abilities.     

Long term exposure to cypermethrin induces nigrostriatal dopaminergic neurodegeneration in adult rats: postnatal exposure enhances the susceptibility during adulthood

The study aimed to investigate the effects of cypermethrin on biochemical, histopathological, and motor behavioral indices of the nigrostriatal dopaminergic system in adult rats treated with or without cypermethrin (1/10 adult dose) during postnatal days 5-19. Spontaneous locomotor activity (SLA) and rotarod tests were performed to assess motor behavior. Levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum, and tyrosine hydroxylase (TH) immunoreactivity and 4′,6-diamidino-2-phenylindole (DAPI)/Fluoro-Jade B staining in the substantia nigra were measured to assess dopaminergic neurodegeneration. Postnatal treated animals did not exhibit significant changes in any measured parameters. The significant reduction in the time of stay on rotarod, spontaneous locomotor activity, dopamine, 3,4-dihydroxyphenylacetic acid, and tyrosine hydroxylase immunoreactivity while an increase in homovanillic acid level and Fluoro-Jade B-positive cells were observed in cypermethrin treated adult rats. These changes were more pronounced in the animals treated with cypermethrin during postnatal days followed by adulthood compared with adulthood alone. The results obtained thus demonstrate that exposure to cypermethrin during adulthood induces dopaminergic neurodegeneration in rats and postnatal exposure enhances the susceptibility of animals to dopaminergic neurodegeneration if rechallenged during adulthood.     

Ovarian hormone withdrawal-induced "depression" in female rats

Approximately 15% of child-bearing women develop postpartum depression (PPD), and many women with PPD experience anxious symptoms. It has been proposed that PPD is precipitated by the dramatic decline in reproductive hormones that occurs just after childbirth. To examine this hypothesis, ovariectomized female Sprague-Dawley rats underwent a hormone-simulated pregnancy (HSP) regimen; during the subsequent hormone withdrawal period, rats were tested in the forced swim test or elevated plus-maze, animal models of depression and anxiety, respectively. The HSP regimen consisted of injections with progesterone and escalating doses of estradiol benzoate for 22 days; control rats received daily vehicle injections. One, two, four or seven days after the last hormone injection, separate groups of rats were tested once on either the forced swim test or the elevated plus-maze. To examine any hormone withdrawal-induced changes in activity levels, spontaneous locomotor activity was measured at the same time points. At 2 and 4 days after the last hormone injection, HSP-treated females displayed significant increases in immobility relative to vehicle-treated females in the forced swim test. Behavior on the elevated plus-maze did not differ between the HSP and control groups at any of the withdrawal time points. There were also no differences in spontaneous locomotor activity between the HSP and control females at any of the withdrawal time points. The results of this study suggest that postpartum hormone withdrawal may contribute to depressive symptoms experienced after giving birth, and that the HSP-hormone withdrawal protocol may provide a useful animal model of PPD.     

Lipopolysaccharide injected to pregnant mice affects behavior of their offspring in adulthood

We studied consequences of maternal immune response on the course of pregnancy and the behavior of adult offspring. Mice in late gestation (day 16-17) were injected with lipopolysaccharide (LPS). Treatment of pregnant mice with high doses of LPS resulted in fetal resorption or stillbirths. Pregnant mice treated with low doses (100 or 300 micrograms/kg) of LPS gave birth to normal numbers of pups. However, behavior of the offspring was altered. Adult offspring of dams injected at a dose of 300 micrograms/kg of LPS traveled longer distances in the open field and spent more time in the central part of the arena, than mice in the control group. Female mice of this group spent more time in open arms of the elevated plus maze, in comparison to female control mice. Results of the Morris water maze test showed impairment of spatial learning and memory in male offspring born to LPS-injected dams. Furthermore, in the nest building test adult mice born from LPS challenged pregnancies constructed worse quality nests, which points to the presence of hippocampal dysfunction. These findings indicate that maternal bacterial infections during pregnancy may alter offspring behavior in adult life.     

Increased sensitivity to the acute effects of MDMA ("ecstasy") in female rats

Behavioral effects of +/-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are relatively well described in humans as well as in animals. However, little is known about gender differences to the effects of MDMA. The aim of our study was to evaluate gender differences in stimulant effects of MDMA (2.5, 5.0, and 10.0 mg/kg subcutaneously (s.c.)) in male and female Wistar rats. We have used three behavioral methods (activity cage, open field, and elevated plus-maze) each describing a different pattern of spontaneous behavior. In the activity cage, 30 min after the MDMA administration, horizontal and vertical locomotor activities were registered for a period of 3 min. In the open field test rats were placed into an arena 15 min after drug treatment and locomotor activity was registered for a period of 30 min. Finally, in the elevated plus-maze test, rats were given MDMA 30 min prior to measurements and subsequently they were tested in the maze for a period of 5 min. In our experiments we observed a dose-dependent locomotion-enhancing effect of MDMA both in male and female rats in both locomotor tests. Female rats were more sensitive to the locomotor-stimulating effect than males in both tests, suggesting higher sensitivity to the stimulatory effect of MDMA. Further on, MDMA increased thigmotaxis in female rats in the open field test and decreased "anxious-like" behavior in the elevated plus-maze in both genders. In conclusion, we observed higher sensitivity of females to the locomotor-stimulant effect of MDMA. Increased sensitivity of females to the behavioral effects of MDMA can be explained by increased reactivity of serotonergic and dopaminergic systems.     

母代高脂饮食对雄性后代小鼠青春期后期运动能力及学习记忆行为的影响

目的:研究母代高脂饮食(high-fat diet,HFD)对雄性后代小鼠青春期后期运动能力及学习记忆行为的影响及机制.方法:通过16周高脂饮食喂养母鼠直至哺乳期结束建立母鼠肥胖模型,以子代雄鼠作为主要研究对象.通过足迹分析和转棒实验研究了子代小鼠的运动协调性,通过旷场实验研究了雄性子代小鼠运动能力的变化,通过水迷宫和...     

Effects of prenatal administration of psychotropic drugs on behavior of developing rats

The effects of prenatal administration of 1 mg/kg d-amphetamine sulfate or 3 mg/kg chlorpromazine HCl to rats from days 12 through 15 of gestation inclusive were studied on behavior of the offspring in the open field, mazes, and operant conditioning. The locomotor activity scores of rats whose mothers received chlorpromazine were significantly lower than those of controls on day 13 after birth but reached a level significantly higher than that of controls on day 18. Offspring of amphetaminetreated mothers had relatively low activity scores early in testing and were delayed in reaching adult activity levels. Although in the mother-goal-maze offspring of both chlorpromazine- and amphetamine-treated mothers generally had shorter latencies than controls, rats whose mothers received chlorpromazine made significantly more errors. These animals also took significantly longer to acquire the bar-press response. No differences among groups were observed in learning or reversal in the T-maze or in performance or extinction of the operant response.     

Chronic mild stress impact: Are females more vulnerable?

Despite the knowledge that women are more susceptible than men to stress-related mental illness, such as major depression, there is no comprehensive estimation of the role of gender in the detrimental effects of chronic stress that might cause depression. Sex differences regarding the association of behavioral parameters with serotonergic and hypothalamic-pituitary-adrenal axis activities were investigated in the chronic mild stress model of depression. Additionally, the impact of chronic mild stress exposure on an additional/novel short-term stressful procedure, such as the forced swim test was examined in male and female rats. Female rats were found to be more vulnerable to chronic mild stress and that was depicted with disruption of sucrose intake, decreases in open field activity, increased corticosterone levels, alteration in estrous cycle and decreased serotonergic activity in hippocampus and hypothalamus. On the contrary, in males the current chronic mild stress protocol elicited only behavioral changes, such as disruption in sucrose intake and decreased open field activity. Interestingly, in response to forced swim test, females previously subjected to chronic mild stress, were found to cope better by exhibiting increased active behavior in the second forced swim test session and higher hypothalamic serotonergic activity in comparison with corresponding males. On the other hand, males were more affected by previous chronic mild stress exposure and that was manifested by decreased active behavior in the first forced swim test session and increased corticosterone levels following second forced swim test session. These data indicate that although females are more vulnerable in the application of chronic mild stress than males, in response to an additional-novel stressor (forced swim test) they show better response. Therefore, both sex/gender and combination of stressful procedures should be carefully considered in the study of the pathophysiology of stress-related mental illnesses.     

Differential effects of i.c.v. microinfusion of agmatine on spatial working and reference memory in the rat

Recent evidence suggests that agmatine, the metabolite of arginine by arginine decarboxylase, exists in the mammalian brain and is a novel neurotransmitter. Exogenous agmatine can modulate behaviour function, including learning and memory. The present study investigated the effects of repeated i.c.v. microinfusion of agmatine (once daily) on the reference and working memory versions of the water maze task, as well as the elevated plus maze and open field. Rats with high (100 μg), but not low (10 μg), dose of agmatine displayed reduced exploratory and locomotor activity in the open field relative to the saline controls on day 1 (received three infusions), but not day 12 (received 14 infusions). The three groups performed similarly on both days in the elevated plus maze tested prior to the open field. In the reference memory version of the water maze task, rats with agmatine treatment at both doses performed as well as the saline controls in the cued navigation (day 2), place navigation (days 3–7) and probe test (day 7). In the working memory version of the water maze task (days 8–11), the two agmatine groups generated markedly shorter path length and took significantly less time to reach the platform at the 180 s, but not 30 s, delay as compared to the saline group. These results demonstrate that repeated agmatine treatment produces transient impairments in exploratory and locomotor activity in the open field in a dose-dependent manner. Agmatine significantly facilitates spatial working memory at a longer delay, but not reference memory, suggesting its differential influence on the two types of spatial learning and memory. The underlying mechanisms need to be explored in the future.