Changes In Exploratory Behavior Research Articles

Insight into JNK Inhibition-based Strategy for the Treatment of Alzheimer's Disease

Background: Existing drugs for the treatment of Alzheimer's disease do not meet the basic requirements. Therefore, it is necessary to search for fundamentally new targets for the discovery of drugs for Alzheimer's disease (AD). When creating approaches to stimulate neurogenesis, such a search is promising to conduct as part of the development of a strategy for targeted regulation of intracellular signal transduction in regeneration-competent cells (RCCs). Moreover, the participation of c-Jun Nterminal kinases (JNK) in the regulation of the functions of the nervous tissue and neuroglial cells is known. Objective: The aim of the work was to study the effect of the JNK inhibitor (IQ-1S) on exploratory behavior and cognitive functions in aged mice (16-month-old male C57BL/6 mice as a model of AD) in combination with the dynamics of shifts in the RCCs functioning (nervous tissue progenitors: neural stem cells (NSCs) and neuronal-committed progenitors (NCPs); neuroglial cells: astrocytes, oligodendrocytes, microglial cells). Methods: The studies were carried out on male C57BL/6 mice aged 16 months as model of Alzheimer's disease. We studied the effect of the JNK inhibitor on exploratory behavior, conditioned reflex activity, and on the functioning of RCCs in the subventricular zone of the cerebral hemispheres (SVZ). NCPs and neuroglial cells of different types were obtained by immunomagnetic separation. Results: We observed significant changes in exploratory behavior and impaired conditioned reflex activity in aged C57BL/6 mice. The administration of the JNK inhibitor led to a significant correction of age-related behavioral and memory disorders in aged mice. At the same time, against the background of JNK inhibition-based therapy, an increase in mitotic activity and the content of both NSCs and NCPs in the SVZ was noted. However, these shifts were more pronounced in committed precursors. The phenomenon of the inhibition of NSC specialization under the influence of a pharmacological agent was also revealed. In addition, the JNK inhibitor caused an increase in the secretion of neurotrophic growth factors by oligodendrocytes and microglial cells. Conclusion: The findings open up prospects for the development of JNK targeting-based approaches for the treatment of AD.

Effects of methylphenidate after a long period of discontinuation include changes in exploratory behavior and increases brain activities of Na+,K+-ATPase and acetylcholinesterase

Methylphenidate (MPH) has been widely misused by children and adolescents who do not meet all diagnostic criteria for attention-deficit/hyperactivity disorder. Since it is not yet known whether MPH can be administered in childhood without consequences in adulthood, in the present study we proposed to investigate the effects of chronic early treatment with MPH after a long period of discontinuation. Wistar male rats were injected with MPH (2 mg/kg, intraperitoneally) or saline solution once daily from 15th to 44th day of life. Two months after the last MPH administration, we evaluated the animal’s performances on a battery of behavior tests. We also tested Na+,K+-ATPase and acetylcholinesterase activities in prefrontal cortex and hippocampus, which may be associated with behavior. Rats treated with MPH during peri-adolescence show changes in exploratory behavior in adulthood in the open field but not in the elevated plus maze and light–dark transition tests. MPH-treated rats showed a lower latency to find the platform in the training phase, as well as a better performance in the test phase in the Morris water maze test. No differences were observed in the object recognition index and working memory. Acetylcholinesterase was increased in prefrontal cortex and hippocampus, while Na+,K+-ATPase was increased only in hippocampus. These findings provide additional evidence that early-life exposure to MPH can have complex effects in adulthood and new basis for understanding the behavioral and neurochemical consequences associated with chronic use of MPH during the development of central nervous system.

Infection with intestinal helminth (Hymenolepis diminuta) impacts exploratory behavior and cognitive processes in rats by changing the central level of neurotransmitters.

Parasites may significantly affect the functioning of the host organism including immune response and gut-brain-axis ultimately leading to alteration of the host behavior. The impact of intestinal worms on the host central nervous system (CNS) remains unexplored. The aim of this study was to evaluate the effect of intestinal infection by the tapeworm Hymenolepis diminuta on behavior and functions of the CNS in rats. The 3 months old animals were infected, and the effects on anxiety, exploration, sensorimotor skills and learning processes were assessed at 18 months in Open Field (OF), Novel Object Recognition (NOR) and the Water Maze (WM) tests. After completing the behavioral studies, both infected and non-infected rats were sacrificed, and the collected tissues were subjected to biochemical analysis. The levels of neurotransmitters, their metabolites and amino acids in selected structures of the CNS were determined by HPLC. In addition, the gene expression profile of the pro- and anti-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-10) was evaluated by Real-Time PCR to determine the immune response within the CNS to the tapeworm infection. The parasites caused significant changes in exploratory behavior, most notably, a reduction of velocity and total distance moved in the OF test; the infected rats exhibited decreased frequency in the central zone, which may indicate a higher level of anxiety. Additionally, parasite infestation improved spatial memory, assessed in the WM test, and recognition of new objects. These changes are related to the identified reduction in noradrenaline level in the CNS structures and less pronounced changes in striatal serotonergic neurotransmission. H. diminuta infestation was also found to cause a significant reduction of hippocampal expression of IL-6. Our results provide new data for further research on brain function during parasitic infections especially in relation to helminths and diseases in which noradrenergic system may play an important role.

Early post-stress administration of MR or GR antagonist in adolescent female rats restored anxiogenic-like behavior and modified the HPA axis response in the adulthood

Several brain structures responsible for controlling stress responses reach maturity during adolescence. Therefore, acute or chronic stress in prepuberty may negatively affect stress responses as well as behavior in adulthood. The hypothalamus–pituitary-adrenal axis (HPA) is part of the stress system whose inhibitory control is regulated by glucocorticoids through mineralocorticoid (MR) and glucocorticoid (GR) receptors. In this study, we aimed to determine whether MR or GR blockade after stress in adolescence prevents changes in exploratory behavior and HPA axis control in adult female rats. Adolescent female rats (26 days old) were submitted to one or seven daily restraint sessions followed by administration of MR (spironolactone) or GR (RU-486) antagonists. At 60 days old, animals were evaluated in the elevated plus maze and at 61 days old rats were subjected to acute stress to evaluate the HPA response. The chronic restraint in the adolescence induced an anxiogenic effect in the adult animals that was reverted by either MR or GR antagonist. In the same way chronic stress reduced the HPA axis activity by blunted corticosterone (CORT) secretion and decreased the activation of Corticotropin Releasing Hormone (CRH) neurons in the paraventricular nucleus. The post-stress blocking of GR independently restored the CORT secretion without effect on central activation. The acute stress in the adolescence had minor enduring effects. We concluded that the use of RU-486 and spironolactone after stress in the early adolescence can improve behavioral changes induced by stress whereas RU-486 only showed effect on the HPA axis response in adulthood.

YAC128 mouse model of Huntington disease is protected against subtle chronic manganese (Mn)-induced behavioral and neuropathological changes

Manganese (Mn) is an essential micronutrient but excessive levels induce neurotoxic effects. Increasing evidence suggests a deficit of bioavailable Mn in Huntington disease (HD), an inherited neurodegenerative disease characterized by motor and cognitive disturbances. Previous studies have shown rescue of some molecular HD phenotypes by acute Mn exposure. This study simultaneously examined the potential for chronic Mn exposure to attenuate HD behavioral phenotypes, and for the HD genotype to offer protection against detrimental effects of chronic Mn exposure. In two independent studies a chronic Mn exposure paradigm was implemented in the YAC128 mouse model of HD and behavior was assessed at several timepoints. Study 1 exposed WT and YAC128 mice to twice weekly subcutaneous injections of 0, 5, 15, or 50 mg/kg MnCl[2] tetrahydrate from 12 to 32 weeks of age. A promising protective effect against motor coordination decline in 5 mg/kg MnCl[2] tetrahydrate-treated YAC128 mice was detected. Study 2 thus exposed WT and YAC128 mice to either 0 or 5 mg/kg MnCl[2] tetrahydrate from 12 to 52 weeks of age (with a partial randomized treatment crossover at 31 weeks). The same protective effect was not observed under these conditions at higher statistical power. We report subtle toxicological changes in exploratory behavior and total activity induced by chronic Mn exposure in WT mice only, despite similar total increases in brain Mn in WT and YAC128 mice. Further, chronic Mn treatment resulted in a 10–12 % decrease in striatal NeuN positive cell density in WT mice but not YAC128 mice, despite vehicle cell counts already being reduced compared to WT mice as expected for the HD genotype. The subtle changes observed in specific outcome measures, but not others, following long-term low-level Mn exposure in WT mice delineate the neurobehavioral and neuropathological effects at the threshold of chronic Mn toxicity. We conclude that these chronic low-dose Mn exposures do not significantly rescue behavioral HD phenotypes, but YAC2128 mice are protected against the subtle Mn-induced behavioral changes and decreased striatal neuron density observed in Mn-exposed WT mice.

Chronic adolescent stress increases exploratory behavior but does not appear to change the acute stress response in adult male C57BL/6 mice

Chronic stress exposure in adolescence can lead to a lasting change in stress responsiveness later in life and is associated with increased mental health issues in adulthood. Here we investigate whether the Chronic Social Instability (CSI) paradigm influences the behavioral and molecular responses to novel acute stressors in mice, and whether it alters physiological responses influenced by the noradrenergic system. Using large cohorts of mice, we show that CSI mice display a persistent increase in exploratory behaviors in the open field test alongside small but widespread transcriptional changes in the ventral hippocampus. However, both the transcriptomic and behavioral responses to novel acute stressors are indistinguishable between groups. In addition, the pupillometric response to a tail shock, known to be mediated by the noradrenergic system, remains unaltered in CSI mice. Ultra-high performance liquid chromatography analysis of monoaminergic neurotransmitter levels in the ventral hippocampus also shows no differences between control or CSI mice at baseline or in response to acute stress. We conclude that CSI exposure during adolescence leads to persistent changes in exploratory behavior and gene expression in the hippocampus, but it does not alter the response to acute stress in adulthood and is unlikely to alter the function of the noradrenergic system.

Effects of hypoxia on the behavior and physiology of kelp forest fishes.

Forecasts from climate models and oceanographic observations indicate increasing deoxygenation in the global oceans and an elevated frequency and intensity of hypoxic events in the coastal zone, which have the potential to affect marine biodiversity and fisheries. Exposure to low dissolved oxygen (DO) conditions may have deleterious effects on early life stages in fishes. This study aims to identify thresholds to hypoxia while testing behavioral and physiological responses of two congeneric species of kelp forest fish to four DO levels, ranging from normoxic to hypoxic (8.7, 6.0, 4.1, and 2.2mg O2 /L). Behavioral tests identified changes in exploratory behavior and turning bias (lateralization), whereas physiological tests focused on determining changes in hypoxia tolerance (pCrit), ventilation rates, and metabolic rates, with impacts on the resulting capacity for aerobic activity. Our findings indicated that copper rockfish (Sebastes caurinus) and blue rockfish (Sebastes mystinus) express sensitivity to hypoxia; however, the strength of the response differed between species. Copper rockfish exhibited reduced absolute lateralization and increased escape time at the lowest DO levels, whereas behavioral metrics for blue rockfish did not vary with oxygen level. Both species exhibited decreases in aerobic scope (as a function of reduced maximum metabolic rate) and increases in ventilation rates to compensate for decreasing oxygen levels. Blue rockfish had a lower pCrit and stronger acclimation response compared to copper rockfish. The differences expressed by each species suggest that acclimatization to changing ocean conditions may vary, even among related species that recruit to the same kelp forest habitat, leading to winners and losers under future ocean conditions. Exposure to hypoxia can decrease individual physiological fitness through metabolic and aerobic depression and changes to anti-predator behavior, with implications for the outcome of ecological interactions and the management of fish stocks in the face of climate change.

Male C57BL6/N and C57BL6/J Mice Respond Differently to Constant Light and Running-Wheel Access.

Previous studies have shown that exposure to circadian disruption produces negative effects on overall health and behavior. More recent studies illustrate that strain differences in the behavioral and physiological responses to circadian disruption exist, even if the strains have similar genetic backgrounds. As such, we investigated the effects of constant room-level light (LL) with running-wheel access on the behavior and physiology of male C57BL6/J from Jackson Laboratories and C57BL6/N from Charles River Laboratories mice. Mice were exposed to either a 12:12 light-dark (LD) cycle or LL and given either a standard home cage or a cage with a running-wheel. Following 6 weeks of LD or LL, their response to behavioral assays (open-field, light-dark box, novel object) and measures of metabolism were observed. Under standard LD, C57BL6/J mice exhibited increased locomotor activity and reduced exploratory behavior compared to C57BL6/N mice. In LL, C57BL6/J mice had greater period lengthening and increased anxiety, while C57BL6/N mice exhibited increased weight gain and no change in exploratory behavior. C57BL6/J mice also decreased exploration with running-wheel access while C57BL6/N mice did not. These results further demonstrate that C57BL/6 substrains exhibit different behavioral and physiological responses to circadian disruption and wheel-running access.

Emergence of an Invariant Representation of Texture in Primate Somatosensory Cortex.

A major function of sensory processing is to achieve neural representations of objects that are stable across changes in context and perspective. Small changes in exploratory behavior can lead to large changes in signals at the sensory periphery, thus resulting in ambiguous neural representations of objects. Overcoming this ambiguity is a hallmark of human object recognition across sensory modalities. Here, we investigate how the perception of tactile texture remains stable across exploratory movements of the hand, including changes in scanning speed, despite the concomitant changes in afferent responses. To this end, we scanned a wide range of everyday textures across the fingertips of rhesus macaques at multiple speeds and recorded the responses evoked in tactile nerve fibers and somatosensory cortical neurons (from Brodmann areas 3b, 1, and 2). We found that individual cortical neurons exhibit a wider range of speed-sensitivities than do nerve fibers. The resulting representations of speed and texture in cortex are more independent than are their counterparts in the nerve and account for speed-invariant perception of texture. We demonstrate that this separation of speed and texture information is a natural consequence of previously described cortical computations.

P.169 The effect of CDNF on N171-82Q mouse model of Huntington`s disease

Manganese (Mn) is an essential micronutrient but excessive levels induce neurotoxic effects. Increasing evidence suggests a deficit of bioavailable Mn in Huntington disease (HD), an inherited neurodegenerative disease characterized by motor and cognitive disturbances. Previous studies have shown rescue of some molecular HD phenotypes by acute Mn exposure. This study simultaneously examined the potential for chronic Mn exposure to attenuate HD behavioral phenotypes, and for the HD genotype to offer protection against detrimental effects of chronic Mn exposure. In two independent studies a chronic Mn exposure paradigm was implemented in the YAC128 mouse model of HD and behavior was assessed at several timepoints. Study 1 exposed WT and YAC128 mice to twice weekly subcutaneous injections of 0, 5, 15, or 50 mg/kg MnCl[2] tetrahydrate from 12 to 32 weeks of age. A promising protective effect against motor coordination decline in 5 mg/kg MnCl[2] tetrahydrate-treated YAC128 mice was detected. Study 2 thus exposed WT and YAC128 mice to either 0 or 5 mg/kg MnCl[2] tetrahydrate from 12 to 52 weeks of age (with a partial randomized treatment crossover at 31 weeks). The same protective effect was not observed under these conditions at higher statistical power. We report subtle toxicological changes in exploratory behavior and total activity induced by chronic Mn exposure in WT mice only, despite similar total increases in brain Mn in WT and YAC128 mice. Further, chronic Mn treatment resulted in a 10–12 % decrease in striatal NeuN positive cell density in WT mice but not YAC128 mice, despite vehicle cell counts already being reduced compared to WT mice as expected for the HD genotype. The subtle changes observed in specific outcome measures, but not others, following long-term low-level Mn exposure in WT mice delineate the neurobehavioral and neuropathological effects at the threshold of chronic Mn toxicity. We conclude that these chronic low-dose Mn exposures do not significantly rescue behavioral HD phenotypes, but YAC2128 mice are protected against the subtle Mn-induced behavioral changes and decreased striatal neuron density observed in Mn-exposed WT mice.

Adenosine A2A Receptors in the Rat Prelimbic Medial Prefrontal Cortex Control Delay-Based Cost-Benefit Decision Making.

Adenosine A2A receptors (A2ARs) were recently described to control synaptic plasticity and network activity in the prefrontal cortex (PFC). We now probed the role of these PFC A2AR by evaluating the behavioral performance (locomotor activity, anxiety-related behavior, cost-benefit decision making and working memory) of rats upon downregulation of A2AR selectively in the prelimbic medial PFC (PLmPFC) via viral small hairpin RNA targeting the A2AR (shA2AR). The most evident alteration observed in shA2AR-treated rats, when compared to sh-control (shCTRL)-treated rats, was a decrease in the choice of the large reward upon an imposed delay of 15 s assessed in a T-maze-based cost-benefit decision-making paradigm, suggestive of impulsive decision making. Spontaneous locomotion in the open field was not altered, suggesting no changes in exploratory behavior. Furthermore, rats treated with shA2AR in the PLmPFC also displayed a tendency for higher anxiety levels in the elevated plus maze (less entries in the open arms), but not in the open field test (time spent in the center was not affected). Finally, working memory performance was not significantly altered, as revealed by the spontaneous alternation in the Y-maze test and the latency to reach the platform in the repeated trial Morris water maze. These findings constitute the first direct demonstration of a role of PFC A2AR in the control of behavior in physiological conditions, showing their major contribution for the control of delay-based cost-benefit decisions.

Effects of the second-generation "bath salt" cathinone alpha-pyrrolidinopropiophenone (α-PPP) on behavior and monoamine neurochemistry in male mice.

Synthetic cathinones ("bath salts") are β-ketone analogs of amphetamines, yet few studies have examined their potential neurotoxic effects. In the current study, we assessed the persistent behavioral and neurochemical effects of exposure to the second-generation synthetic cathinone α-pyrrolidinopropiophenone (α-PPP). Male, Swiss-Webster mice were exposed to α-PPP (80mg/kg) using a binge-like dosing regimen (QID, q2h). Behavior was assessed 4-5days after the dosing regimen, and neurochemistry was assessed the following day. Behavior was studied using the elevated plus maze, Y-maze, and novel object recognition tests. Regional levels of dopamine, serotonin, norepinephrine, and the major dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were determined in the prefrontal cortex and striatum using high-pressure liquid chromatography. Additional experiments assessed the time courses of the effects of α-PPP on locomotor activity and core temperature using telemetry. Exposure to α-PPP significantly impaired performance in the Y-maze, decreased overall exploratory activity in the novel object recognition test, and resulted in regionally specific depletions in monoamine neurochemistry. In contrast, it had no significant effect on elevated plus maze performance or object discrimination in the novel object recognition test. The locomotor-stimulant effects of α-PPP were comparable to cocaine (30mg/kg), and α-PPP (80mg/kg) did not induce hyperthermia. α-PPP exposure results in persistent changes in exploratory behavior, spatial working memory, and monoamine neurochemistry. This research highlights potential dangers of α-PPP, including potential neurotoxicity, and suggests that the mechanisms underlying the persistent untoward effects of the cathinones may be distinct from those of the amphetamines.

Exploratory behavior of a native anuran species with high invasive potential.

Exploratory behavior can be a key component of survival in novel or changing environments, ultimately determining population establishment. While many studies have investigated the behavior of wild animals in response to novel food items or objects, our understanding of how they explore novel environments is limited. Here, we examine how experience affects the foraging behavior of a species with high invasive potential. In particular, we investigate the movement and behavior of cane toads as a function of experience in a novel environment, and how the presence of food modulates exploration. Cane toads, from a population in their native range, were repeatedly tested in a large, naturalistic arena with or without food present. Both groups exhibited significant but different changes in exploratory behavior. While toads in an environment without food reduced exploratory behavior over trials, those with food present increased both food intake per trial and the directness of their paths to food, resulting in fewer approaches to food patches over time. Our results suggest that cane toads learn patch location and provide preliminary evidence suggesting toads use spatial memory, not associative learning, to locate food. In sum, we show that with experience, cane toads alter their behavior to increase foraging efficiency. This study emphasizes the role of learning in foraging in cane toads, a characteristic that may have facilitated their success as invaders.

Ethovision™ analysis of open field behaviour in rats following bilateral vestibular loss.

Bilateral vestibular loss (BVL) causes a unique behavioural syndrome in rodents, with symptoms such as locomotor hyperactivity and changes in exploratory behaviour. Many of these symptoms appear to be indirect consequences of the loss of vestibular reflex function and are difficult to explain. Although such symptoms have been reported before, there have been few systematic studies of the effects of BVL using automated digital tracking systems in which many behavioural symptoms can be measured simultaneously with high precision. In this study, data were obtained from rats with BVL induced by intratympanic sodium arsanilate injections (n = 7) or sham injections (n = 8) and their behaviour in the open field was measured at 3 days and 23 days post-injection using Ethovision™ tracking software. BVL rats demonstrated reduced thigmotaxis, with more time spent in the central zones. Twenty-three days post-injection, BVL animals showed increased locomotor activity in the open field. The increase in activity was also reflected in the number of transitions between each zone of the field. In addition to increased activity, BVL animals showed increased whole body rotations following lesions. Using linear discriminant analysis (LDA) and random forest classification (RFC), we were able to show that the indirect behavioural effects of BVL, excluding direct measurement of vestibular reflex function, could correctly predict whether animals had received a BVL with a high degree of accuracy at both day 3 and day 23 post-BVL (83% and 100% for LDA, and 100% and 100% for RFC, respectively). RFC has been similarly successful in classifying other hyperactivity syndromes such as attention deficit hyperactivity disorder. These results suggest that BVL results in a unique behavioural signature that can identify vestibular loss in rats even without direct vestibular reflex measurements.

Neutrophil gelatinase-associated lipocalin and microglial activity are associated with distinct postoperative behavioral changes in rats

Neutrophil gelatinase-associated lipocalin (NGAL) has recently gained interest as a marker for neuroinflammation and associated behavioral dysfunction. We aimed to explore the link between NGAL and behavior in a rat model of postoperative cognitive dysfunction (POCD).Material collected in two previous studies on POCD was analyzed and associated with outcomes for exploratory behavior and spatial learning. Plasma and hippocampal NGAL and microglial activity were analyzed. Pearson’s correlations and backward linear regression were performed to study the associations between behavioral parameters, NGAL concentrations, and microglial activity.Plasma and hippocampal NGAL were increased following surgery. Plasma NGAL was associated with impaired spatial learning only, microglial activity was associated with exploratory behavior only, while hippocampal NGAL was associated with both behavioral aspects. Spatial learning was best predicted by a model containing plasma NGAL concentrations and hippocampal microglial activity.NGAL may serve as a sensitive marker in connecting the peripheral inflammatory state to POCD, while postoperative changes in exploratory behavior are better reflected by hippocampal neuroinflammation. These findings warrant further exploration in the role of NGAL in development of postoperative behavioral deficits.

Impairment of exploratory behavior and spatial memory in adolescent rats in lithium-pilocarpine model of temporal lobe epilepsy.

Cognitive impairment in six-week -old rats has been studied in the lithium-pilocarpine model of adolescent temporal lobe epilepsy in humans. The pilocarpine-treated rats (n =21) exhibited (a) a decreased exploratory activity in comparison with control rats (n = 20) in the open field (OP) test and (b) a slower extinction of exploratory behavior in repeated OP tests. The Morris Water Maze (MWM) test showed that the effect of training was less pronounced in the pilocarpine-treated rats, which demonstrated disruption of predominantly short-term memory. Therefore, our study has shown that lithium-pilocarpine seizures induce substantial changes in exploratory behavior and spatial memory in adolescent rats. OP and MWM tests can be used in the search of drugs reducing cognitive impairments associated with temporal lobe epilepsy.

Inhibiting cholesterol degradation induces neuronal sclerosis and epileptic activity in mouse hippocampus.

Elevations in neuronal cholesterol have been associated with several degenerative diseases. An enhanced excitability and synchronous firing in surviving neurons are among the sequels of neuronal death in these diseases and also in some epileptic syndromes. Here, we attempted to increase neuronal cholesterol levels, using a short hairpin RNA to suppress expression of the enzyme cytochrome P450 family 46, subfamily A, polypeptide 1 gene (CYP46A1). This protein hydroxylates cholesterol and so facilitates transmembrane extrusion. A short hairpin RNA CYP46A1construction coupled to the adeno-associated virus type 5 was injected focally and unilaterally into mouse hippocampus. It was selectively expressed first in neurons of the cornu ammonis (hippocampus) (CA)3a region. Cytoplasmic and membrane cholesterol increased, and the neuronal soma volume increased and then decreased before pyramidal cells died. As CA3a pyramidal cells died, interictal electroencephalographic (EEG) events occurred during exploration and non-rapid eye movement sleep. With time, neuronal death spread to involve pyramidal cells and interneurons of the CA1 region. CA1 neuronal death was correlated with a delayed local expression of phosphorylated tau. Astrocytes were activated throughout the hippocampus and microglial activation was specific to regions of neuronal death. CA1 neuronal death was correlated with distinct aberrant EEG activity. During exploratory behaviour and rapid eye movement sleep, EEG oscillations at 7-10 Hz (theta) could accelerate to 14-21 Hz (beta) waves. They were accompanied by low-amplitude, high-frequency oscillations of peak power at ~300 Hz and a range of 250-350 Hz. Although episodes of EEG acceleration were not correlated with changes in exploratory behaviour, they were followed in some animals by structured seizure-like discharges. These data strengthen links between increased cholesterol, neuronal sclerosis and epileptic behaviour.

The changes in exploratory behavior and Fgf2 gene expression in cells of the rat brain after the early postnatal administration of bacterial lipopolysaccharide

Infectious diseases at early ages are often followed by impairments in cognitive functions in children and adolescents. A possible mechanism of these impairments is an altered production of proteins that are involved in the regulation of neuroplasticity in brain cells. One of these proteins is the basic fibroblast growth factor (FGF2). In the present study, we examined the behavior in the “open field” test and FGF2 mRNA production in the medial prefrontal cortex, ventral and dorsal hippocampus, and amygdala of 22-and 23-day-old rats that were injected with bacterial lipopolysaccharide at a dose of 25 µg/kg on days 14, 16, and 18 after birth. We observed decreased exploratory activity and increased static movement compared to the control animals that were injected with a pyrogen-free physiological solution. Impaired behavior was associated with the lower expression of the Fgf2 gene in cells of the medial prefrontal cortex compared to that observed in the intact rats.

Effects Of Ferulic Acid On Exploratory Behavior And Locomotor Activity In Rats

Summary Ferulic acid (FA), called also hydroxycinnamic acid, is a polyphenol compound found in many foods such as coffee, apples, rice, oats and wheat. It acts as an antioxidant but its other activities in vivo have not been well studied as a whole. The aim of the present study was to investigate the effects of FA on exploratory behavior and locomotor activity in male Wistar rats. FA was administrated orally (20 mg/kg) to different groups of rats for 7, 14, 21 and 30 days. These groups were compared respectively with saline-treated controls. At the end of each experimental period, the changes in exploratory behavior and locomotor activity were recorded in an Opto Varimex apparatus (Columbus Instruments, USA). The number of horizontal and vertical movements recorded every minute for the first 5 min served as a measure of exploratory activity and habituation to the new environment. The total number of movements during the first 5 min and during the whole 10-min period of observation was used as a measure of locomotor activity. It was found that FA at all doses for all treatment periods did not significantly affect exploratory behavior and locomotor activity of rats, when compared with the saline-treated controls. At all testing periods, FA did not disturb habituation. As habituation is considered an elementary form of learning, the present study suggested that FA did not disturb the memory and learning processes in rats.

Effects ofAronia melanocarpafruit juice on exploratory behaviour and locomotor activity in rats

The main bioactive substances in Aronia melanocarpa fruit juice (AMFJ) are polyphenols (flavonoids, procyanidins, and phenolic acids). A great number of polyphenols are able to traverse the blood-brain barrier. In recent years more attention is drawn to the ability of these substances to influence central nervous system functions. The aim of the present study was to investigate the effects of AMFJ on exploratory behaviour and locomotor activity in male Wistar rats. AMFJ was administered orally for 7, 14, 21, and 30 days at three increasing doses (2.5, 5, and 10 ml kg−1). The changes in exploratory behaviour and locomotor activity were recorded in an Opto Varimex apparatus. It was found that the low doses of AMFJ (2.5 and 5 ml kg−1) for all treatment periods did not significantly affect exploratory behaviour and locomotor activity of rats compared to the saline-treated controls. AMFJ at the highest dose of 10 ml kg−1 had no significant effect on exploration and locomotion for the treatment periods of 7 and 14 days, while for the periods of 21 and 30 days it significantly decreased the number of horizontal and vertical movements, which might be the result of a sedative effect. At all the doses and testing periods, AMFJ did not disturb the progressive decrease in motor behaviour, suggesting habituation.