Behavioral Tests Of Anxiety Research Articles

Overnutrition during Pregnancy and Lactation Induces Gender-Dependent Dysmetabolism in the Offspring Accompanied by Heightened Stress and Anxiety.

Maternal obesity and gestational diabetes predispose the next generation to metabolic disturbances. Moreover, the lactation phase also stands as a critical phase for metabolic programming. Nevertheless, the precise mechanisms originating these changes remain unclear. Here, we investigate the consequences of a maternal lipid-rich diet during gestation and lactation and its impact on metabolism and behavior in the offspring. Two experimental groups of Wistar female rats were used: a control group (NC) that was fed a standard diet during the gestation and lactation periods and an overnutrition group that was fed a high-fat diet (HF, 60% lipid-rich) during the same phases. The offspring were analyzed at postnatal days 21 and 28 and at 2 months old (PD21, PD28, and PD60) for their metabolic profiles (weight, fasting glycemia insulin sensitivity, and glucose tolerance) and euthanized for brain collection to evaluate metabolism and inflammation in the hypothalamus, hippocampus, and prefrontal cortex using Western blot markers of synaptic dynamics. At 2 months old, behavioral tests for anxiety, stress, cognition, and food habits were conducted. We observed that the female offspring born from HF mothers exhibited increased weight gain and decreased glucose tolerance that attenuated with age. In the offspring males, weight gain increased at P21 and worsened with age, while glucose tolerance remained unchanged. The offspring of the HF mothers exhibited elevated levels of anxiety and stress during behavioral tests, displaying decreased predisposition for curiosity compared to the NC group. In addition, the offspring from mothers with HF showed increased food consumption and a lower tendency towards food-related aggression. We conclude that exposure to an HF diet during pregnancy and lactation induces dysmetabolism in the offspring and is accompanied by heightened stress and anxiety. There was sexual dimorphism in the metabolic traits but not behavioral phenotypes.

Structural brain abnormalities in endothelial nitric oxide synthase-deficient mice revealed by high-resolution magnetic resonance imaging.

Endothelial nitric oxide synthase (eNOS) produces nitric oxide, which is essential for a variety of physiological functions in the brain. Previous work has demonstrated the detrimental effects of eNOS deficiency on brain function in male eNOS knockout (eNOS KO) mice. However, the effect of eNOS deficiency on brain structure and any association between these effects and sex is unknown. This study used three-dimensional high-resolution ex vivo magnetic resonance imaging and behavioral tests of anxiety and cognitive performance to investigate structure-function relationships in the brain of female and male eNOS KO mice in young adulthood. While there were no differences in anxiety-like behavior or locomotion, there was a sex-specific deficit in contextual fear memory retention in male, but not in female, eNOS mice compared to wild-type controls. Moreover, we found that eNOS deficiency induced changes in multiple brain regions that are involved in learning and fear memory including the hippocampus, amygdala, hypothalamus, and areas of the cortex. Several of these MRI-detectable neuroanatomical changes were dependent on sex. The observation that eNOS deficiency impacts brain structure at an early age demonstrates the importance of eNOS for healthy brain development.

Effects of tooth loss on anxiety‐like behaviors in Heterocephalus glaber

Tooth loss is an ailment affecting a large percentage of the population, particularly individuals of lower socioeconomic status and the elderly. Extensive tooth loss is known to result in anatomical changes in the face, including atrophy of masticatory muscles and decreases in mandibular and maxillary bone density, as well as volumetric changes within the brain. Human studies have reported strong correlations between tooth loss and levels of both anxiety and depression. However, little has been reported to date regarding the effect of dental health on emotional states, with only sparse information available from animal models regarding the psychiatric effects of tooth loss.Our study investigated the short‐term effects of tooth loss on anxiety‐like behaviors using Heterocephalus glaber, an animal with extensive sensory dedication to and behavioral reliance on its incisors. Adult naked mole‐rats underwent either tooth extraction or sham surgeries, followed by testing in both an open field maze and elevated plus maze in the weeks following. As there are no known studies to date that have utilized this animal model in behavioral tests of anxiety, our study provides critical information about the methodologies and modifications necessary to ascertain these important translational behavioral states so that future researchers can apply similar tests in other fields such as neurodegeneration, aging, and oncology.We hypothesized that tooth extraction will result in greater anxiety‐like behaviors, manifesting in various ways: greater defecation in the mazes, more time spent in the outer regions of the open field maze, and less time in the open arms of the elevated plus maze. The study demonstrated a trend towards tooth extraction increasing anxiety‐like behaviors in naked mole‐rats when investigated using the open field maze paradigm. There is evidence that, with an increase in sample sizes, this research will make evident the causal relationship of tooth loss and anxiety. Future research will investigate the long‐term behavioral changes associated with extensive tooth loss and the neurocircuitry associated with these behavioral alterations. Uncovering these details will provide potential therapeutic targets for negating the mental health difficulties associated with deficits in dental health.

In vitro inhibition of acetylcholinesterase and monoamine oxidase by Syzygium cumini leaves extract and preliminary assessment in animal models

Syzygium cumini (Myrtaceae) is a tropical tree used in traditional medicines to treat several diseases. All parts of S. cumini are used for medicinal purposes and present antioxidant potential. In this study, we evaluated the phytochemical composition of the ethanolic extract of S. cumini leaves (EESC) and its biological activity in vitro and in vivo regarding some effects on the central nervous system. Behavioral tests of anxiety, depression, and memory were performed with mice and the cerebral cortex used to evaluate lipoperoxidation and the acetylcholinesterase activity ex vivo. The EESC showed the presence of flavonoids, tannins, and gallic acid esters-4-O-glucurosides, detected for the first time in the species. The EESC presented antioxidant capacity in vitro with EC50 of 82.8 μg/mL in the DPPH assay and IC50 of 1.27 μg/mL in the lipoperoxidation test. The EESC inhibited the in vitro acetylcholinesterase and monoamine oxidase activities presenting IC50 of 44.54 and 432.7 μg/mL, respectively. However, the EESC did not show significant effects on the behavioral tests and ex vivo assays. Our results confirm the potential of EESC as a source of bioactive compounds acting on important target enzymes for central nervous system disorders, but the in vivo effects must be better evaluated.

Effect of Estrous Cycle on Behavior of Females in Rodent Tests of Anxiety.

Anxiety disorders are more prevalent in women than in men. In women the menstrual cycle introduces another variable; indeed, some conditions e.g., premenstrual syndrome, are menstrual cycle specific. Animal models of fear and anxiety, which form the basis for research into drug treatments, have been developed almost exclusively, using males. There remains a paucity of work using females and the available literature presents a confusing picture. One confound is the estrous cycle in females, which some authors consider, but many do not. Importantly, there are no accepted standardized criteria for defining cycle phase, which is important given the rapidly changing hormonal profile during the 4-day cycle of rodents. Moreover, since many behavioral tests that involve a learning component or that consider extinction of a previously acquired association require several days to complete; the outcome may depend on the phase of the cycle on the days of training as well as on test days. In this article we consider responsiveness of females compared to males in a number of commonly used behavioral tests of anxiety and fear that were developed in male rodents. We conclude that females perform in a qualitatively similar manner to males in most tests although there may be sex and strain differences in sensitivity. Tests based on unconditioned threatening stimuli are significantly influenced by estrous cycle phase with animals displaying increased responsiveness in the late diestrus phase of the cycle (similar to the premenstrual phase in women). Tests that utilize conditioned fear paradigms, which involve a learning component appear to be less impacted by the estrous cycle although sex and cycle-related differences in responding can still be detected. Ethologically-relevant tests appear to have more translational value in females. However, even when sex differences in behavior are not detected, the same outward behavioral response may be mediated by different brain mechanisms. In order to progress basic research in the field of female psychiatry and psychopharmacology, there is a pressing need to validate and standardize experimental protocols for using female animal models of anxiety-related states.

Reduced exploratory behavior in neuronal nucleoredoxin knockout mice

Nucleoredoxin is a thioredoxin-like redoxin that has been recognized as redox modulator of WNT signaling. Using a Yeast-2-Hybrid screen, we identified calcium calmodulin kinase 2a, Camk2a, as a prominent prey in a brain library. Camk2a is crucial for nitric oxide dependent processes of neuronal plasticity of learning and memory. Therefore, the present study assessed functions of NXN in neuronal Nestin-NXN-/- deficient mice. The NXN-Camk2a interaction was confirmed by coimmunoprecipitation, and by colocalization in neuropil and dendritic spines. Functionally, Camk2a activity was reduced in NXN deficient neurons and restored with recombinant NXN. Proteomics revealed reduced oxidation in the hippocampus of Nestin-NXN-/- deficient mice, including Camk2a, further synaptic and mitochondrial proteins, and was associated with a reduction of mitochondrial respiration. Nestin-NXN-/- mice were healthy and behaved normally in behavioral tests of anxiety, activity and sociability. They had no cognitive deficits in touchscreen based learning & memory tasks, but omitted more trials showing a lower interest in the reward. They also engaged less in rewarding voluntary wheel running, and in exploratory behavior in IntelliCages. Accuracy was enhanced owing to the loss of exploration. The data suggested that NXN maintained the oxidative state of Camk2a and thereby its activity. In addition, it supported oxidation of other synaptic and mitochondrial proteins, and mitochondrial respiration. The loss of NXN-dependent pro-oxidative functions manifested in a loss of exploratory drive and reduced interest in reward in behaving mice.

Does the provision of environmental enrichment affect the behaviour and welfare of captive snakes?

There is a wealth of evidence demonstrating the benefits of environmental enrichment across a range of different animal species. However, there is comparatively little such research into the effect of enrichment provision on captive reptiles. The aim of this study was therefore to ascertain if an increase in environmental complexity was beneficial to the behaviour and welfare of corn snakes (Pantherophis guttatus). The study used a combination of behavioural observations in the home enclosure, behavioural tests of anxiety, and a preference test. The snakes used the enrichment when it was available to them and enriched snakes showed changes in general behaviour reflective of improved welfare. However, the anxiety tests revealed few effects of enrichment provision on performance. In contrast, the snakes exhibited a strong preference for the enriched enclosure when given a choice. These findings suggest that the provision of environmental complexity to the enclosure was beneficial to the behaviour and welfare of captive corn snakes. We therefore recommend enrichment should be used when keeping captive snakes.

Ciliary neurotrophic factor is a key sex-specific regulator of depressive-like behavior in mice

Ciliary neurotrophic factor (CNTF) is produced by astrocytes and promotes neurogenesis and neuroprotection. Little is known about the role of CNTF in affective behavior. We investigated whether CNTF affects depressive- and anxiety-like behavior in adult mice as tested in the forced swim, sucrose preference and elevated-T maze tests. Female wild type CNTF+/+ mice more readily developed behavioral despair with increased immobility time and decreased latency to immobility in the forced swim test than male CNTF+/+ littermates. The lack of CNTF in CNTF-/- mice had an opposite effect on depressive-like behavior in female mice (reduced immobility time and increased sucrose preference) vs. male mice (increased immobility time). Female wildtype mice expressed more CNTF in the amygdala than male mice. Ovariectomy increased CNTF expression, as well as immobility time, which was significantly reduced in CNTF-/- mice, suggesting that CNTF mediates overiectomy-induced immobility time, possibly in the amygdala. Progesterone but not 17-β estradiol inhibited CNTF expression in cultured C6 astroglioma cells. Progesterone treatment also reduced CNTF expression in the amygdala and decreased immobility time in female CNTF+/+ but not in CNTF-/- mice. Castration did not alter CNTF expression in males nor their behavior. Lastly, there were no effects of CNTF on the elevated T-maze, a behavioral test of anxiety, suggesting that a different mechanism may underlie anxiety-like behavior. This study reveals a novel CNTF-mediated mechanism in stress-induced depressive-like behavior and points to opportunities for sex-specific treatments for depression, e.g. progesterone in females and CNTF-stimulating drugs in males.

Effects of a hydroethanolic extract of Boophone disticha bulb on anxiety-related behaviour in naive BALB/c mice

Ethnopharmacological relevanceBoophone disticha is one of the most important medicinal bulbs of Southern Africa. Previous in vitro studies have shown that it's crude ethanolic extracts and some alkaloidal phytoconstituents possesses high affinity for the serotonin transporter protein (SERT) and serotonin receptor 1a (5HT1a) which are both implicated in the pathogenesis and treatment of anxiety disorders. However, there are no in vivo studies that validates the anxiolytic actions of the plant. Aim of the studyThis study was therefore set to determine the anxiolytic-like activity of an orally administered hydroethanolic extract of B. disticha bulbs in naive mice using the behavioural tests of anxiety. Materials and methodsNaïve adult male BALB/c mice were randomly placed into five treatment groups (n=6–10): vehicle control (10ml/kg 0.9% NaCl), positive control (1mg/kg diazepam) and the hydroethanolic extract of B. disticha (10, 25 and 40mg/kg p.o.). Souk test, elevared plus maze and open field tests were used to evaluate the anxiolytic-like activity of the B. disticha extract. ResultsDiazepam-treated mice exhibited higher number of sector visits and line crossings in the ST, rearings in the OF and head dips in the EPM than the control (p<0.05). B. disticha extract treated groups expressed higher sector visits at 10mg/kg, and, unprotected head dips at 25mg/kg in the ST, as well as, open arm time entries at 10mg/kg dose, and unprotected head dips at all doses in the EPM than the control group (p<0.05). The 25mg/kg B. disticha dose group exhibited highest anxiolytic-like activity in both the ST and OF, while the 10mg/kg was most active in the EPM. ConclusionThe extract of B. disticha exerted good anxiolytic-like activity in both the ST and OF at medium dose (25mg/kg), while the low dose (10mg/kg) showed prominent anxiolytic-like activity in the EPM.

Rats exposed to 2.45 GHz of non-ionizing radiation exhibit behavioral changes with increased brain expression of apoptotic caspase 3

In recent years there has been a tremendous increase in use of Wi-Fi devices along with mobile phones, globally. Wi-Fi devices make use of 2.4GHz frequency. The present study evaluated the impact of 2.45GHz radiation exposure for 4h/day for 45days on behavioral and oxidative stress parameters in female Sprague Dawley rats. Behavioral tests of anxiety, learning and memory were started from day 38. Oxidative stress parameters were estimated in brain homogenates after sacrificing the rats on day 45. In morris water maze, elevated plus maze and light dark box test, the 2.45GHz radiation exposed rats elicited memory decline and anxiety behavior. Exposure decreased activities of super oxide dismutase, catalase and reduced glutathione levels whereas increased levels of brain lipid peroxidation was encountered in the radiation exposed rats, showing compromised anti-oxidant defense. Expression of caspase 3 gene in brain samples were quantified which unraveled notable increase in the apoptotic marker caspase 3 in 2.45GHz radiation exposed group as compared to sham exposed group. No significant changes were observed in histopathological examinations and brain levels of TNF-α. Analysis of dendritic arborization of neurons showcased reduction in number of dendritic branching and intersections which corresponds to alteration in dendritic structure of neurons, affecting neuronal signaling. The study clearly indicates that exposure of rats to microwave radiation of 2.45GHz leads to detrimental changes in brain leading to lowering of learning and memory and expression of anxiety behavior in rats along with fall in brain antioxidant enzyme systems.

Consequences of long-term treatment with agomelatine on depressive-like behavior and neurobiological abnormalities in pinealectomized rats

Previous data have shown that the rat model of melatonin deficit can cause a number of neurobiological aberrations. The aim of the present study was to determine whether the antidepressant drug agomelatine, a MT1/MT2 melatoninergic receptor agonist/5-HT2C receptor antagonist is able to prevent some of the behavioral, biochemical and cellular abnormalities induced by pinealectomy. The injection of agomelatine (40mg/kg, i.p. for 5 weeks)/vehicle started after pinealectomy/sham procedure in Wistar rats. Animals were tested in different behavioral tests for anxiety and depression during the period of agomelatine treatment (chronic effect) and two months later (plastic effect). The effect of agomelatine on KCl-evoked serotonin (5-HT) release from the hippocampus, the activity of the hypothalamic–pituitary–adrenal (HPA) axis and neuronal loss in pinealectomized rats were assessed. Our results showed that agomelatine not only did not prevent the disturbed emotional arousal/anxiety behavior in pinealectomized rats during the treatment but the enhanced motor activity and decreased anxiety state was still observed two months after the discontinuation of treatment. However, the drug corrected a depressive-like behavior (chronic and plastic effect), alleviated the enhanced KCl-evoked 5-HT release in the hippocampus, recovered the suppressed negative feedback inhibition of HPA axis and exerted a neuroprotection in pinealectomized rats. Our findings suggest that pinealectomy can model melancholic depression disorder while the antidepressant action of agomelatine is associated with a correction of 5-HT release in the hippocampus, dysregulated HPA system and neuroprotection in limbic structures.

Cannabinoids & Stress: Impact of HU-210 on behavioral tests of anxiety in acutely stressed mice

Anxiety disorders are one of the most prevalent classes of mental disorders affecting the general population, but current treatment strategies are restricted by their limited efficacy and side effect profiles. Although the cannabinoid system is speculated to be a key player in the modulation of stress responses and emotionality, the vast majority of current research initiatives had not incorporated stress exposure into their experimental designs. This study was the first to investigate the impact of exogenous cannabinoid administration in an acutely stressed mouse model, where CD1 mice were pre-treated with HU-210, a potent CB1R agonist, prior to acute stress exposure and subsequent behavioral testing. Exogenous cannabinoid administration induced distinct behavioral phenotypes in stressed and unstressed mice. While low doses of HU-210 were anxiolytic in unstressed subjects, this effect was abolished when mice were exposed to an acute stressor. The administration of higher HU-210 doses in combination with acute stress exposure led to severe locomotor deficits that were not previously observed at the same dose in unstressed subjects. These findings suggest that exogenous cannabinoids and acute stress act synergistically in an anxiogenic manner. This study underlies the importance of including stress exposure into future anxiety-cannabinoid research due to the differential impact of cannabinoid administration on stressed and unstressed subjects.

Chronic renal insufficiency does not induce behavioral and cognitive alteration in rats

In humans, chronic kidney disease (CKD) is associated with cognitive decline, increase in anxiety, or depression. The underlying mechanisms of these changes remain unclear. The aim of this study was to elucidate whether and how experimentally induced long-term CKD affects cognitive functions in rats.Thirty male Wistar rats underwent 5/6 nephrectomy (5/6 Nx), an established model of CKD, or sham surgery. Development of CKD was monitored using biochemical analyses and confirmed by renal histology. Behavioral tests of anxiety, depression and spatial behavior were performed before, and at 3 and 9months after the surgery.CKD in 5/6 Nx rats was characterized by significant decrease of renal function, e.g., glomerular filtration rate, and progressive glomerulosclerosis, tubular atrophy, and interstitial fibrosis; and increased plasma uremic toxins. Mortality was higher in 5/6 Nx rats in comparison with controls. Compared to control group, the surviving 5/6 Nx rats presented similar general locomotor activity, depression traits, and spatial abilities (p=0.43, p=0.84, p=0.71, respectively). At 9months, lower anxiety in the light–dark box test was observed in 5/6 Nx rats if compared with the control group (p=0.02).Despite the development of progressive CKD in 5/6 Nx rats, no expected behavioral changes were observed. Further experimental studies associating behavioral responses to severity of CKD are definitely needed to confirm the solely psychosocial aspect background of CKD-associated cognitive impairment in humans.

Anxiety- and depression-like phenotype of hph-1 mice deficient in tetrahydrobiopterin

Decreased tetrahydrobiopterin (BH4) biosynthesis has been implicated in the pathophysiology of anxiety and depression. The aim of this study was therefore to characterise the phenotype of homozygous hph-1 (hph) mice, a model of BH4 deficiency, in behavioural tests of anxiety and depression as well as determine hippocampal monoamine and plasma nitric oxide levels. In the elevated zero maze test, hph mice displayed increased anxiety-like responses compared to wild-type mice, while the marble burying test revealed decreased anxiety-like behaviour. This was particularly observed in male mice. In the tail suspension test, hph mice of both sexes displayed increased depression-like behaviours compared to wild-type counterparts, whereas the forced swim test showed a trend towards increased depression-like behaviours in male hph mice, but significant decrease in depression-like behaviours in female mice. This study provides the first evidence that congenital BH4 deficiency regulates anxiety- and depression-like behaviours. The altered responses observed possibly reflect decreased hippocampal serotonin and dopamine found in hph mice compared to wild-type mice, but also reduced nitric oxide formation. We propose that the hph-1 mouse may be a novel tool to investigate the role of BH4 deficiency in anxiety and depression.

Vomeronasal organ lesion disrupts social odor recognition, behaviors and fitness in golden hamsters.

Most studies support the viewpoint that the vomeronasal organ has a profound effect on conspecific odor recognition, scent marking and mating behavior in the golden hamster (Mesocricetus auratus). However, the role of the vomeronasal organ in social odor recognition, social interaction and fitness is not well understood. Therefore, we conducted a series of behavioral and physiological tests to examine the referred points in golden hamster. We found that male hamsters with vomeronasal organ lesion showed no preference between a predator odor (the anal gland secretion of the Siberian weasels (Mustela sibirica) and putative female pheromone components (myristic acid and palmitic acid), but were still able to discriminate between these 2 kinds of odors. In behavioral tests of anxiety, we found that vomeronasal organ removal causes female hamsters to spend much less time in center grids and to cross fewer center grids and males to make fewer crossings between light and dark boxes than sham-operated controls. This indicates that a chronic vomeronasal organ lesion induced anxious responses in females. In aggressive behavioral tests, we found that a chronic vomeronasal organ lesion decreased agonistic behavior in female hamsters but not in males. The pup growth and litter size show no differences between the 2 groups. All together, our data suggested that vomeronasal organ ablation disrupted the olfactory recognition of social chemosignals in males, and induced anxiety-like and aggressive behavior changes in females. However, a vomeronasal organ lesion did not affect the reproductive capacity and fitness of hamsters. Our studies may have important implications concerning the role of the vomeronasal organ in golden hamsters and also in rodents.

Exposition to tannery wastewater did not alter behavioral and biochemical parameters in Wistar rats

There are scarce data on the neurotoxicity in mammalian induced by tannery wastewaters. Previously, the anxiogenic effect of tannery wastewater was demonstrated in mice, while wastewater submitted to photoelectrooxidation (PEO) process treatment did not affect the anxiety state. Considering that species may response differently to xenobiotics, the aim of the present work was to study the effects of exposure to tannery wastewaters (non-PEO or PEO-treated) on behavioral and neurochemical markers in another species of laboratory animals, specifically Wistar rats. Male Wistar rats were given free access to water bottles containing non-PEO or PEO-treated tannery wastewaters (0.1, 1 and 5% in drinking water). During the exposure, behavioral tests of anxiety (elevated plus-maze, neophobia, open field and light–dark box), depression (forced swimming) and memory (inhibitory avoidance, novel object and discriminative avoidance) were performed. On the 30th day, brain structures were dissected out to evaluate cellular oxidative state (hippocampus, cerebellum and striatum) and acetylcholinesterase activity (hippocampus and striatum). Exposure to tannery effluent with or without photoelectrochemical treatment did not alter any behavioral and neurochemical parameters evaluated. Our data indicate that Wistar rats may not be an adequate species for ecotoxicological studies involving tannery effluents and that POE treatment did not generate other toxic compounds.

Alpha-Asarone, a Major Component ofAcorus gramineus, Attenuates Corticosterone-Induced Anxiety-Like Behaviours via Modulating TrkB Signaling Process

We investigated the anxiolytic-like activity of α-asarone (AAS) from Acorus gramineus in an experimental rat model of anxiety induced by repeated administration of the exogenous stress hormone corticosterone (CORT). The putative anxiolytic effect of AAS was studied in behavioral tests of anxiety, such as the elevated plus maze (EPM) test and the hole-board test (HBT) in rats. For 21 consecutive days, male rats received 50, 100, or 200 mg/kg AAS (i.p.) 30 min prior to a daily injection of CORT. Dysregulation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Daily AAS (200 mg/kg) administration increased open-arm exploration significantly in the EPM test, and it increased the duration of head dipping activity in the HBT. It also blocked the increase in tyrosine hydroxylase (TH) expression in the locus coeruleus (LC) and decreased mRNA expression of brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, in the hippocampus. These results indicated that the administration of AAS prior to high-dose exogenous CORT significantly improved anxiety-like behaviors, which are associated with modification of the central noradrenergic system and with BDNF function in rats. The current finding may improve understanding of the neurobiological mechanisms responsible for changes in emotions induced by repeated administration of high doses of CORT or by elevated levels of hormones associated with chronic stress. Thus, AAS did exhibit an anxiolytic-like effects in animal models of anxiety.

Juvenile stress enhances anxiety and alters corticosteroid receptor expression in adulthood

BackgroundExposure to stress in early life is correlated with the development of anxiety disorders in adulthood. The underlying mechanisms are not fully understood, but an imbalance in corticosteroid receptor (CR) expression in the limbic system, particularly the hippocampus, has been implicated in the etiology of anxiety disorders. However, little is known about how prepubertal stress in the so called “juvenile” period might alter the expression of these receptors.AimsTherefore, the aim of this study was to investigate how stress experienced in the juvenile phase of life altered hippocampal expression of CRs and anxiety behaviors in adulthood.Materials and methodsWe used a rodent model to assess the effects of juvenile stress on hippocampal CR expression, and performance in three behavioral tests of anxiety in adulthood.ResultsJuvenile stress (JS) increased anxiety-like behavior on the elevated plus maze, increased mineralocorticoid receptor (MR) expression, and decreased the ratio of glucocorticoid receptor (GR) to MR expression in the hippocampus of adult animals. Females demonstrated lower levels of anxiety-type behavior and increased activity in three behavioral tests, and had greater expression of GR and GR:MR ratio than males, regardless of treatment.Discussion and conclusionThese results demonstrate that JS can alter the expression and balance of CRs, providing a potential mechanism for the corresponding increase in anxiety behavior observed in adulthood. Further evidence for the role of CR expression in anxiety is provided by sex differences in anxiety behavior and corresponding alterations in CR expression.

Role of serotonin in zebrafish (Danio rerio) anxiety: Relationship with serotonin levels and effect of buspirone, WAY 100635, SB 224289, fluoxetine and para-chlorophenylalanine (pCPA) in two behavioral models

Serotonin (5-HT) is a neurotransmitter that is involved in many behavioral functions, including the organization of defense, and its putative pathological correlate, anxiety and stress disorders. Recently, behavioral tests for anxiety have been proposed in zebrafish. Exposure to the novel tank test or to the light/dark test increased extracellular fluid 5-HT content in the brain; anxiety-like behavior correlated positively with 5-HT content in the novel tank test, while the correlation was negative in the light/dark test. Acute treatment with a low dose of fluoxetine was anxiolytic in the geotaxis test and anxiogenic in the scototaxis test, while treatment with a higher dose produced a hyperlocomotor effect in both tasks. Buspirone and WAY 100635 were anxiolytic in both tests, while SB 224289 was anxiolytic in the geotaxis and slightly anxiogenic in the scototaxis test. Serotonin depletion with pCPA was anxiogenic in the geotaxis and anxiolytic in scototaxis. These results underline the differential sensitivity of these tasks to assess serotonergic agents; alternatively, serotonin might regulate zebrafish behavior differently in the novel tank test and in the light/dark test.

Anxiolytic effects of ethanol are partially related to a reduced expression of adenylyl cyclase 5 but not to μ-opioid receptor activation in rat nucleus accumbens

Anxiolytic effects of alcohol participate in the reinforcing properties of the drug, in which nucleus accumbens (NAcc) is implicated. The opioidergic system in NAcc is considered a main pathway involved in the emotional responses of animals: rats microinjected with morphine in NAcc and the systemic administration of μ-opioid receptors (MOR) agonists yield low anxiety scores in the elevated plus maze (EPM), a behavioral test of anxiety. However, the specific participation of NAcc MOR in the anxiolytic effect of ethanol has not been studied. AC5, a cAMP-synthezising adenylyl-cyclase, is highly expressed in NAcc; it is negatively coupled to MOR and has been implicated in anxiety levels of animals.We evaluated the anxiolytic effects of an intra-gastric administration of ethanol (2.5g/kg) in animals subjected to EPM at 1, 4, and 8h after drug or water exposure. Locomotion was assayed with the open-field test; we also measured accumbal AC5 and MOR mRNA levels by RT-PCR. After 1h, ethanol-exposed animals showed anxiolytic-like behavior, as well as decreased and increased AC5 and MOR expression in NAcc, respectively. Intra-accumbal injection of β-funaltrexamine (FNA), a MOR antagonist, did not block ethanol-induced anxiolysis, rather it induced a tendency to increase anxiety levels in the water-exposed group. FNA partially decreased accumbal AC5 expression in ethanol-treated rats. We concluded that AC5 in NAcc is participating in the emotional effects of ethanol; that MOR was not mediating the drug-induced AC5 reduction in NAcc nor the ethanol-induced anxiolysis. MOR only might be involved in basal levels of anxiety of animals.