Examination of empathy-like behaviour in nicotine-preferring rat lines.

AIM: Addiction is an important global health issue, impacting also addicts environment and society. Empathy plays crucial role in establishing successful social relationships and is a fundamental component of social life. The aim of this study is to investigate how nicotine preferring (NP) strain and oral forced nicotine administration affects empathy-like behaviour in rats, with gender differences. MATERIALS AND METHODS: Sprague-Dawley NP rats (10 males/10 females) and wild-type control rats (10 males/10 females) were used. Behavioural tests were administered to all rats before and after oral forced nicotine administration. The behavioural tests were completed in the fourth week of nicotine administration. Anxiety levels that could affect empathy-like behaviour were evaluated with open field, elevated plus maze tests and with blood cortisol levels. Oxytocin receptor and arginine vasopressin (AVP) levels, which have been shown to be related to empathy-like behaviour, were examined in the prefrontal cortex and amygdala regions using the enzyme-linked immunoassay method. RESULTS: It was observed that males from the NP strain showed less empathy-like behaviour than all other groups, and nicotine administration did not cause a significant change in the results. Higher levels of locomotor activity (LA) were found in control females than in all other groups. Blood nicotine and corticosterone levels were higher in NP rats. No significant differences were found in AVP and oxytocin receptor levels in the prefrontal cortex and amygdala.Conclusions It was found that coming from an addicted strain particularly reduces empathy-like behaviour in males.

Daily Consumption of High-Polyphenol Olive Oil Enhances Hippocampal Neurogenesis in Old Female Rats.

OBJECTIVE: The aim of this study is to evaluate the effect of daily consumption of high-polyphenol (HP) olive oil on neurogenesis by investigating neuronal cell proliferation and maturation in the hippocampus of old rats, and to evaluate the relationship between neurogenesis, spatial memory, and anxiety-like behavior. METHODS: A total of 34 female, 20-22-month-old Sprague Dawley rats were divided into three groups: control group, low-polyphenol (LP) group, and high-polyphenol (HP) group. The animals were fed distilled water, LP olive oil and HP-extra virgin olive oil, respectively for 6 weeks using an oral gavage. At 43 days, animals were tested using the Morris Water Maze to evaluate spatial memory, and the Open-field test to evaluate anxiety-like behavior. Neural cell proliferation in the dentate gyrus (DG) was determined by BrdU labeling and Nestin protein expression. Neuronal maturation was determined by NeuN labeling. Synaptic density in the hippocampus and prefrontal cortex was examined by measuring Synaptophysin (SYN) levels. Hippocampal Calbindin levels were measured to assess cellular calcium metabolism. RESULTS: Daily consumption of HP olive oil significantly improved cell proliferation and neuronal maturation in the DG of old rats. HP-olive oil significantly increased SYN levels in the prefrontal cortex, and nestin and calbindin levels in the hippocampus (p < 0.05). LP olive oil diet has shown no effect on any parameter (p > 0.05). We also did not find any statistically significant difference between the groups in terms of spatial memory and anxiety-like behavior (p > 0.05). CONCLUSION: Our study is first to show that daily consumption of HP-olive oil enhances hippocampal neurogenesis in old rats, which has been confirmed by proliferation and maturation biomarkers. In addition, increased SYN and calbindin levels showed that the generated cells were also functionally developed in the HP group. We suggest that daily consumption of HP olive oil may have beneficial effects on brain aging by triggering neurogenesis.

Repeated acetaminophen administration damaged hippocampal tissue but did not affect prefrontal cortex or anxiety behaviors.

Acetaminophen is one of the most widely used over­the­counter drugs worldwide for the treatment of pain and fever. Although acetaminophen use is known to impair hippocampus­related learning and memory, its effect on anxiety is not clear. Insulin­like growth factor­1 (IGF­1) and matrix metalloproteinase­2 (MMP2) are important for cellular survival, maintenance and tissue integrity. The aim of this study was to investigate the dose­dependent effects of acetaminophen on anxiety levels as well as on hippocampus, prefrontal cortex and liver tissue. Doses of 100, 200 and 400 mg/kg acetaminophen were administered to male Sprague Dawley rats for 11 days and anxiety tests were conducted on the last day. Twenty­four hours after the last acetaminophen administration, all animals were sacrificed and hippocampus, prefrontal cortex and liver tissues were removed for analyses. Hippocampal IGF­1 and MMP2 levels were shown to decrease only at the highest dose of acetaminophen, which was accompanied by pathological changes in histology. The prefrontal cortex was not affected. Behavioral analyses also did not indicate changes in anxiety levels in the rats. Liver IGF­1 and MMP2 levels decreased in all experimental groups. Serum alanine aminotransferase and aspartate aminotransferase levels increased in the 200 mg/kg and 400 mg/kg acetaminophen groups. Our findings showed that varying doses of acetaminophen did not affect the prefrontal cortex or anxiety levels. Further research is needed to elucidate the hippocampal and hepatic protective roles of IGF­1 and MMP2 in acetaminophen toxicity and their potential use in therapeutic approaches.

A combination of ketogenic diet and voluntary exercise ameliorates anxiety and depression-like behaviors in Balb/c mice.

The positive effects of both ketogenic diet (KD) and regular voluntary exercise on anxiety and depression behavior have been recently reported in rodent animals, but the effects of pairing a KD with exercise on depression and anxiety are unknown. In this study, we aimed to investigate the effects of combination of KD and regular voluntary exercise on anxiety and depression-like behavior in Balb/c mice. We've demostrated that anxiety and depression levels decreased in KD-exercised (KD-Ex) mice. ß-hydroxybutyrate (BHB) levels increased while glucose, insulin levels and LDL/HDL ratio decreased in KD-Ex mice. There was a negative correlation between BHB and the time spent in the closed arms of elevated plus maze (EPM) or the time spent in periphery walls of open field test (OFT) and the immobility time in forced swim test (FST) which all of them are indicators of low depression and anxiety levels. There was a positive correlation between LDL/HDL ratio and the time spent in the closed arms of EPM or the immobility time in FST. The immobility time in FST was positively correlated with insulin while the mobility time in FST was negatively correlated with glucose. In conclusion, these results suggest that decline in anxiety and depression-like behaviors resulted from KD with regular voluntary exercise may be associated with increased BHB levels and decreased LDL/HDL ratio and insulin or glucose levels. Further research is necessary for our understanding of the mechanisms by which pairing a KD with voluntary exercise influences brain and behavior.

Regular aerobic exercise increased VEGF levels in both soleus and gastrocnemius muscles correlated with hippocampal learning and VEGF levels.

Physical exercise improves learning and memory abilities by increasing the levels of several growth factors in the hippocampus. One growth factor, vascular endothelial growth factor (VEGF), is primarily produced in the muscles and not only increases in the periphery during exercise but can also cross the blood-brain barrier. The aim of this study is to investigate the effects of regular aerobic chronic exercise on different types of muscle fibers and the relationships between learning/memory and muscle induced-VEGF. Following a one-week adaptation period, male rats underwent treadmill training at a speed of 8 m/min for 30 min daily, 3 days a week for 6 weeks. Memory functions were evaluated using the Morris water maze. VEGF, superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels were measured in type 1 and type 2 muscle fibers and VEGF levels were also measured in the hippocampus. Exercise positively affected both learning and memory and also increased VEGF levels in both muscle fiber types. Muscle VEGF levels positively correlate with hippocampal learning and hippocampal VEGF levels. Exercise reduced both SOD and MDA levels in type 1 and type 2 muscle fibers, whereas GPx levels decreased only in type 2 muscle fibers. Our findings suggest that regular aerobic exercise elevates VEGF levels and diminishes oxidative stress in both fiber types. Exercise-induced VEGF levels in both type 1 and 2 muscle fibers appear to be associated with the positive effect of exercise on learning and memory function and is accompanied by an increase in VEGF levels in the hippocampus. Further research is needed to elucidate the exact mechanism by which fiber type-specific VEGF mediates hippocampal neurogenesis and angiogenesis.Physical exercise improves learning and memory abilities by increasing the levels of several growth factors in the hippocampus. One growth factor, vascular endothelial growth factor (VEGF), is primarily produced in the muscles and not only increases in the periphery during exercise but can also cross the blood-brain barrier. The aim of this study is to investigate the effects of regular aerobic chronic exercise on different types of muscle fibers and the relationships between learning/memory and muscle induced-VEGF. Following a one-week adaptation period, male rats underwent treadmill training at a speed of 8 m/min for 30 min daily, 3 days a week for 6 weeks. Memory functions were evaluated using the Morris water maze. VEGF, superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels were measured in type 1 and type 2 muscle fibers and VEGF levels were also measured in the hippocampus. Exercise positively affected both learning and memory and also increased VEGF levels in both muscle fiber types. Muscle VEGF levels positively correlate with hippocampal learning and hippocampal VEGF levels. Exercise reduced both SOD and MDA levels in type 1 and type 2 muscle fibers, whereas GPx levels decreased only in type 2 muscle fibers. Our findings suggest that regular aerobic exercise elevates VEGF levels and diminishes oxidative stress in both fiber types. Exercise-induced VEGF levels in both type 1 and 2 muscle fibers appear to be associated with the positive effect of exercise on learning and memory function and is accompanied by an increase in VEGF levels in the hippocampus. Further research is needed to elucidate the exact mechanism by which fiber type-specific VEGF mediates hippocampal neurogenesis and angiogenesis.

Magnesium Citrate Increases Pain Threshold and Reduces TLR4 Concentration in the Brain.

Magnesium is being investigated in various clinical conditions and has shown to be effective in some chronic pain models. However, it is not clear if oral magnesium use affects pain perception in acute pain. TLR4's (toll-like receptor) role in pain perception has emerged through its role in immune pathways and ion channels. The aim of this study is to investigate the effect of a single oral dose of magnesium citrate on pain conduction and whether with magnesium, the expression of TLR4 changes in the acute phase. Following a single dose of 66-mg/kg magnesium citrate administration to male Balb-c mice, pain perception (via hot-plate test), motor conduction (via electrophysiological recording, forelimb grip strength, rotarod and open-field tests), and emotional state (via elevated plus maze and forced swim test) were evaluated. In behavioral experiments, the control group was compared with applied magnesium for three different time groups (4, 8, 24 h). TLR4 expression was measured in four groups: control, magnesium (Mg), hot plate (HP), and Mg + HP. Hot plate latency was prolonged in the magnesium group (p < 0.0001) and electrophysiological recordings (p < 0.001) and forelimb grip strength measurement (p < 0.001) determined motor latency. Compared with the untreated hot plate group, TLR4 levels was lower in the brain (p = 0.023) and higher in the sciatic nerve (p = 0.001) in the magnesium-treated hot plate group. Consequently, the study indicated a single dose of magnesium citrate appeared to cause weakening in the transmission and perception of nociceptive pain. TLR4 may act as a regulator in magnesium's effects on pain perception.

Magnesium Acetyl Taurate Prevents Tissue Damage and Deterioration of Prosocial Behavior Related with Vasopressin Levels in Traumatic Brain Injured Rats.

AIM: To investigate the effects of different magnesium forms on tissue damage, cognitive and emotional behavioural impairment after mild traumatic brain injury (TBI). MATERIAL AND METHODS: Rats were divided into 5 groups (control, trauma, magnesium sulphate, magnesium citrate, magnesium acetyl taurate) and following head trauma, empathy-like behaviour, anxiety-like behaviour (elevated plus maze and open field tests), and depression (forced swim test) were measured. The rats were then sacrificed 12 days later. Oxytocin, vasopressin and receptors levels in the amygdala and prefrontal cortex regions were measured. Histopathological damage (with haematoxylin-eosin staining) and apoptosis (with caspase-3 immunohistochemistry) was evaluated. RESULTS: Following head trauma, anxiety-like behaviour and depression tests did not change; empathy-like behaviour deteriorated on the 3rd day and improved gradually on the 6th and 12th days. Oxytocin, vasopressin and vasopressin v1b receptor levels decreased in the amygdala; morphological damage and apoptosis were significant. Magnesium acetyl taurate effectively ameliorated histopathological deteriorations and improved vasopressin and v1b receptor levels in the amygdala. Transient deterioration of empathy-like behaviour was impeded only in magnesium taurate treatment. CONCLUSION: Magnesium acetyl taurate can be a promising candidate agent to prevent structural and functional damage in traumatic brain injury.

Empathy as a Concept from Bench to Bedside: A Translational Challenge.

Empathy is a multidimensional paradigm, and there currently is a lack of scientific consensus in its definition. In this paper, we review the possibility of compromising data during behavioral neuroscience experiments, including but not limited to those who study empathy. The experimental protocols can affect, and be affected by, empathy and related processes at multiple levels. We discuss several points to help researchers develop a successful translational pathway for behavioral research on empathy. Despite varying in their focus with no widely accepted model, current rodent models on empathy have provided sound translational explanations for many neuropsychiatric proof-of-concepts to date. Research has shown that empathy can be influenced by many parameters, some of which are to be reviewed in this paper. We emphasize the future importance of consistency in modeling proof of concept; efforts to create a multidisciplinary group which would include both bench scientists and clinicians with expertise in neuropsychiatry, and the consideration of empathy as an independent variable in animal behavioral experimental designs which is not the mainstream practice at present.

The Chronic Use of Magnesium Decreases VEGF Levels in the Uterine Tissue in Rats.

Vascular endothelial growth factor (VEGF) is the most important regulator of angiogenesis which serves to provide sufficient blood supply, and can trigger both physiological and pathological angiogenesis. Recent studies have shown that VEGF increases in gynecological diseases (such as endometriosis, ovarian, and endometrial cancers) and is a prognostic factor in these pathologies. Therefore, VEGF should be maintained at appropriate levels. Magnesium is used in many gynecological practices (such as eclampsia, preeclampsia, dysmenorrhea, and climacteric symptoms) and the mechanisms of action are still under investigation. Redox status, which can be regulated by magnesium, was shown to affect VEGF expression. The aim of this study was to evaluate the effects of chronic magnesium use on VEGF and oxidative status in the uterus. Magnesium sulfate was administered to rats at doses of 30 mg/kg (intramuscular) for 2 weeks. VEGF, Superoxide dismutase (SOD), Glutathione peroxidase (GPx), and Malondialdehyde (MDA) levels were measured using ELISA; vascular and cellular alterations were determined by histology in the uterine tissue at the metoestrus phase. In the uterine tissue of Mg-treated subjects, magnesium levels increased while VEGF, SOD, GPx, and MDA levels decreased without histological changes. There was a negative correlation between uterine tissue magnesium levels and VEGF, SOD, GPx, and MDA levels. Consequently, the results of this study demonstrated that regular magnesium use decreased VEGF levels in uterus. Decreased VEGF levels were associated with decreased uterine oxidative stress. Chronic magnesium usage may protect the uterine tissue from certain diseases in which angiogenesis is critical.

Mild-intensity Exercise Triggers VEGF in the Digestive Tract Via Both Hypoxic and Nonhypoxic Mechanisms

Abstract Hypoxia occurs in the splanchnic region during exercise associated with sympathetic activity. In the elderly, vascular insufficiency and low vascular endothelial growth factor (VEGF) expression are observed. Compared to young people, sympathetic signals of older individuals are blunted and more resistant to splanchnic blood flow alterations during exercise. VEGF induces vasodilation responses and hence may retain blood in the splanchnic vascular bed. We hypothesized that regular mild-intensity exercise triggers weak VEGF expression in the digestive tract of the elderly. The effects of exercise on the levels of VEGF, superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA) and total antioxidant capacity (T-AOC) in the stomach, jejunum, ileum and colon tissues were evaluated. With exercise, the VEGF levels in the stomach and colon increased. Although the SOD, GPx, and MDA levels decreased in the stomach, they increased in the colon. T-AOC increased in the stomach and there was no change in the jejunum, ileum and colon. The hypoperfusion during exercise was not equal in all regions of the gastrointestinal tract in the aged subjects. Hypoxia and other exercise-related mechanisms could have led to this VEGF induction. The stomach, jejunum, and ileum might have developed resistance to ischemia. The induction of VEGF may be beneficial in aging-associated impaired gastrointestinal homeostasis and neovascularization.

Nicotine increased VEGF and MMP2 levels in the rat eye and kidney.

Chronic cigarette smoking affects many tissues negatively. Nicotine in tobacco has negative effects on tissues, kidneys, and eyes especially, where microcirculation is vitally important for the survival and functioning. It is known that appropriate vascular endothelial growth factor (VEGF) and (matrix metalloproteinase 2) MMP2 levels are required for suitable vascularity and enough microcirculation. The aim of this study was to investigate the effect of nicotine on VEGF and MMP2 levels in kidney and eyes, where microcirculation is very important for their function. The nicotine was given into drinking water, to male and female rats for 6 weeks. During the first 2 weeks, the nicotine concentration was 10 mg/L, then was given at a fixed dose of 20 mg/L until the end of the experiment. The VEGF and MMP2 levels were increased in kidney tissue of both genders as a result of given nicotine. MMP2 levels were also increased in the eye tissue for both genders similarly. However, VEGF levels increased in the eye tissue with nicotine in males, whereas it did not change in females. The use of nicotine made VEGF and MMP2 levels increase in kidney tissue in both genders of rats. This increase in VEGF was observed only in male eye tissue, not in females. According to our findings, it can be suggested that nicotine has negative effects on microvascular circulation by increasing VEGF and MMP2 levels. In addition, it should be pointed out that estrogen might have protective effects on female eye tissue. Further studies are necessary to understand the complex relationship between the role of nicotine and estrogen on eye and kidney tissues.

Regular Aerobic Voluntary Exercise Increased Oxytocin in Female Mice: The Cause of Decreased Anxiety and Increased Empathy-Like Behaviors

Background: It is known that regular physical activity reduces anxiety. Low anxiety levels affect mood, emotions, and empathy. Oxytocin is a powerful hormone that regulates social interaction, sexual reproduction, maternal­infant bonding, milk release, empathy, and anxiety. Empathy is an important behavior in the living community; and also important for sportsmen during sportive competition and daily living life, because sportsmen are also role model of people. Aims: To investigate the effects of voluntary physical activity on oxytocin, anxiety, and empathy levels as well as the relationship between them. Study Design: Animal experiment. Methods: Male and female mice were made to exercise in running wheel cages for 6 weeks. Their empathy and anxiety levels were evaluated by using Helping Behavior test and elevated plus maze and open field test, respectively. And then the brain and blood oxytocin levels were measured. Results: Empathy-like behavior was improved in both genders of the exercise groups (door-opening time decreased in both genders of exercise groups, p for both=0.0001). As a response to exercise, both the brain and serum oxytocin levels increased in female mice (both of p=0.0001); however, in males, oxytocin levels increased in only the brain (p<0.05). Anxiety levels decreased in all the exercise groups (increased time spent in the middle area of open field test, both genders, p=0.002; increased time spent in the open arms of elevated plus maze test, females p=0.004, males p=0.0001). There was a strong negative correlation between serum oxytocin levels and door opening time of helping behavior equipment, and moderate negative correlation was found between the brain oxytocin levels and door-opening time of helping behavior equipment in females. However, there was no correlation between both the brain and serum oxytocin levels and empathy behavior in males. But there were very strong positive correlations between low anxiety indicators and both the brain and serum oxytocin levels in both the genders. Conclusion: Voluntary physical activity decreases anxiety and increases empathy-like behavior in mice; which is associated with increased oxytocin levels in female mice but not in male mice. Further research is required to investigate the mechanisms of exercise effect on anxiety and empathic brain pathways in males.

Dose-Dependent Absorption Profile of Different Magnesium Compounds.

Magnesium, one of the basic elements for the human body, is necessary for many physiological functions. Magnesium deficiency is widely observed as a result of the reduced nutrient content of foods, over-cooking, diseases, drugs, alcohol, and caffeine consumption. Taking a dietary supplement is necessary magnesium deficiency. It has been demonstrated that absorption of organic magnesium compounds is better than absorption of inorganic compounds. The aim of this study is to investigate transitions to tissues of different organic magnesium compounds in different doses and whether there is a difference in the organic acid-bounded compounds (magnesium citrate and magnesium malate) and the amino acid-bounded compounds (magnesium acetyl taurate and magnesium glycinate), associated with transition and bioavailability. In addition, the effects of split dosages of high doses in a high volume of solvent on tissue magnesium levels are being investigated, because galenic formulation problems are regarded to prepare convenient dosage that can be taken once a day. All magnesium compounds were administered as three different doses, 45, 135, and 405 mg/70 kg elemental magnesium, were given per orally to Balbc mice. In a second set of experiments, 405 mg/70 kg high dose was divided into two doses of 202.5 mg/70 kg each and administered every 12 h. Brain, muscle tissues, and serum magnesium levels measured in all experimental groups and control 24 h later. Brain magnesium levels were found increased in all magnesium acetyl taurate administered subjects. Magnesium citrate increased muscle and brain magnesium levels in a dose-independent manner. We showed that dividing high doses of daily administered magnesium compounds did not sufficiently increase tissue magnesium levels. Although passive paracellular mechanism by solvent drag is the main mechanism of Mg absorption, other factors (electrochemical gradient effects, transcellular transporter mechanisms, magnesium status) should be effective on our results. It is necessary for further research on long-term administration of different magnesium compounds and their effect on other tissues.

Timeline (Bioavailability) of Magnesium Compounds in Hours: Which Magnesium Compound Works Best?

Magnesium is an element of great importance functioning because of its association with many cellular physiological functions. The magnesium content of foods is gradually decreasing due to food processing, and magnesium supplementation for healthy living has become increasingly popular. However, data is very limited on the bioavailability of various magnesium preparations. The aim of this study is to investigate the bioavailability of five different magnesium compounds (magnesium sulfate, magnesium oxide, magnesium acetyl taurate, magnesium citrate, and magnesium malate) in different tissues. Following a single dose 400 mg/70 kg magnesium administration to Sprague Dawley rats, bioavailability was evaluated by examining time-dependent absorption, tissue penetration, and the effects on the behavior of the animals. Pharmacokinetically, the area under the curve calculation is highest in the magnesium malate. The magnesium acetyl taurate was found to have the second highest area under the curve calculation. Magnesium acetyl taurate was rapidly absorbed, able to pass through to the brain easily, had the highest tissue concentration level in the brain, and was found to be associated with decreased anxiety indicators. Magnesium malate levels remained high for an extended period of time in the serum. The commonly prescribed dietary supplements magnesium oxide and magnesium citrate had the lowest bioavailability when compared to our control group. More research is needed to investigate the bioavailability of magnesium malate and acetyl taurate compounds and their effects in specific tissues and on behavior.

Acetaminophen (paracetamol) affects empathy-like behavior in rats: Dose-response relationship.

Empathy is the ability to recognize, process and respond to another's emotional state and empathic functions have been linked with a multitude of cognitive and affective processes. Impaired empathy has been linked to aggression and criminal behavior in society. Acetaminophen (paracetamol) is among the most common nonprescription (over the counter) analgesics in the world and has been already linked to reducing empathic behavior in humans. The aim of this study is to investigate the effects of acetaminophen on empathy-like behavior in Sprague Dawley rats, and we further explored the underlying mechanisms by analyzing empathy related neurohormones, e.g. oxytocin and vasopressin, in association with acetaminophen exposure in rats. Empathic behavior was assessed 30 min following acetaminophen administration (100, 200, and 400 mg/kg). The impact of single and repeated acetaminophen administrations on empathy-like behavior and anxiety level were evaluated separately. Empathy-like behavior was reduced with a single high dose of acetaminophen. Subsequent low dose administration of acetaminophen also reduced empathy-like behavior. In this study we also showed that acetaminophen decreased oxytocin and vasopressin levels in the prefrontal cortex and amygdalae. We found a negative correlation between delay in door opening time and measured prefrontal cortex oxytocin levels; we adjudged the latency in door opening time as enhanced empathic behavior which seemingly suggested the existence of a mechanism between empathy-like behavior and the prefrontal oxytocin. We observed that both a single high dose or repeated low dose administrations of acetaminophen reduced empathy-like behavior in correlation with a decrease in oxytocin and vasopressin levels in the prefrontal cortex and amygdala. Further research is needed to investigate the role of acetaminophen on the other empathic brain pathways.

The effects of acute foot shock stress on empathy levels in rats.

Empathy defined as the ability to understand and the share the feelings, thoughts, and attitudes of another, is an important skill in survival and reproduction. Among many factors that affect empathy include psychological stress, anxiety states. The aim of this study was to investigate the impact of acute psychological stress on empathic behavior and its association with oxytocin and vasopressin levels in amygdala and prefrontal cortex. Rats were subjected to 0.2 mA (low) and 1.6 mA (high) intensity of foot shock stress for duration of 20 min. Empathic behavior was found to be improved as a response to low intensity stress, but not to high intensity stress. As a response to lower intensity stress, vasopressin was increased in prefrontal cortex and amygdala; oxytocin was increased in only prefrontal cortex, and corticosterone levels increased in general. Anxiety indicators did not change in low intensity stress group yet; high intensity stress group demonstrated a lesser degree of anxiety response. High intensity stress group stayed unexpectedly more active in middle area of elevated plus maze test equipment, which may support impaired executive decision making abilities in the setting of high anxiety states. Further research is needed to investigate gender effects, the role of dopaminergic system and other stress related pathways in acute stress.

Regular aerobic exercise correlates with reduced anxiety and incresed levels of irisin in brain and white adipose tissue.

We have recently shown that regular voluntary aerobic exercised rats have low levels of anxiety. Irisin is an exercise-induced myokine that is produced by many tissues; and the role it plays in anxiolytic behavior is unknown. In this study we aimed to investigate the correlation between anxiety like behavior and irisin levels following regular voluntary aerobic exercise in male mice. We've have shown that anxiety levels decreased in exercised mice, while irisin levels increased in the brain, brown adipose tissue, white adipose tissue, kidney, and pancreas tissues. No significant difference of irisin levels in the liver, muscle and serum were detected in the exercise group, when compared to controls. In addition, there was a strong positive correlation between brain irisin levels and activity in middle area of open field test and in the open arms of elevated plus maze test; both which are indicators of low anxiety levels. Our results suggest that decrease in anxiolytic behavior due to regular voluntary exercise may be associated with locally produced brain irisin. White adipose tissue irisin levels also correlated very strongly with low anxiety. However, no serum irisin increase was detected, ruling out the possibility of increased peripheral irisin levels affecting the brain via the bloodstream. Further research is necessary to explain the mechanisms of which peripheral and central irisin effects anxiety and the brain region affected.