Open-field Behavior Research Articles

Ghrelin system of the brain participates in control of emotional, explorative behavior and motor activity in rats rearing in conditions of social isolation stress

Wistar rats were rearing in conditions of social isolation from others beginning with 20th day of life till adulthood (90-100 days). In adult rats, a conditioned place preference (CPP) of ethanol (0.5 g/kg ip) was trained, and behavior in open field, elevated plus maze and intruder-resident test was examined. Intranasal administration of [D-Lys3]-GHRP-6, a peptide ghrelin antagonist (10 µg in 20 µl), to isolated rats blocked formation and expression (recovery) of CPP of ethanol that supported participation of ghrelin system in regulation of positive reinforcement activated by ethanol. Intranasal administration of ghrelin (20 µg in 20 µl) to rats reared in conditions of social isolation produced a typical anxiogenic effect, elevated exploratory activity, aggression signs and reduction of communicative behavior. In rats reared in conditions of social isolation, [D-Lys3]-GHRP-6, a ghrelin antagonist, possessed anxiolytic effect, reduced explorative activity, communicative behavior and aggression. It is concluded that ghrelin system of the brain participates in control of emotional, explorative behavior and motor activity in rats rearing in conditions of social isolation stress. (For citation: Shabanov PD, Vinogradov PM, Lebedev AA, et al. Ghrelin system of the brain participates in control of emotional, explorative behavior and motor activity in rats rearing in conditions of social isolation stress. Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(4):38-45. doi: 10.17816/RCF15438-45).

Finasteride inhibited brain dopaminergic system and open-field behaviors in adolescent male rats.

Finasteride inhibits the conversion of testosterone to dihydrotestosterone. Because androgen regulates dopaminergic system in the brain, it could be hypothesized that finasteride may inhibit dopaminergic system. The present study therefore investigates the effects of finasteride in adolescent and early developmental rats on dopaminergic system, including contents of dopamine and its metabolites (dihydroxy phenyl acetic acid and homovanillic acid) and tyrosine hydroxylase expressions both at gene and protein levels. Meanwhile, open-field behaviors of the rats are examined because of the regulatory effect of dopaminergic system on the behaviors. Open-field behaviors were evaluated by exploratory and motor behaviors. Dopamine and its metabolites were assayed by liquid chromatography-mass spectrometry. Tyrosine hydroxylase mRNA and protein expressions were determined by real-time qRT-PCR and western blot, respectively. It was found that in adolescent male rats, administration of finasteride at doses of 25 and 50mg/kg for 14days dose dependently inhibited open-field behaviors, reduced contents of dopamine and its metabolites in frontal cortex, hippocampus, caudate putamen, nucleus accumbens, and down-regulated tyrosine hydroxylase mRNA and protein expressions in substantia nigra and ventral tegmental area. However, there was no significant change of these parameters in early developmental rats after finasteride treatment. These results suggest that finasteride inhibits dopaminergic system and open-field behaviors in adolescent male rats by inhibiting the conversion of testosterone to dihydrotestosterone, and imply finasteride as a potential therapeutic option for neuropsychiatric disorders associated with hyperactivities of dopaminergic system and androgen.

Induction of chronic migraine phenotypes in a rat model after environmental irritant exposure.

Air pollution is linked to increased emergency department visits for headache and migraine patients frequently cite chemicals or odors as headache triggers, but the association between air pollutants and headache is not well understood. We previously reported that chronic environmental irritant exposure sensitizes the trigeminovascular system response to nasal administration of environmental irritants. Here, we examine whether chronic environmental irritant exposure induces migraine behavioral phenotypes. Male rats were exposed to acrolein, a transient receptor potential channel ankyrin-1 (TRPA1) agonist, or room air by inhalation for 4 days before meningeal blood flow measurements, periorbital cutaneous sensory testing, or other behavioral testing. Touch-induced c-Fos expression in trigeminal nucleus caudalis was compared in animals exposed to room air or acrolein. Spontaneous behavior and olfactory discrimination was examined in open-field testing. Acrolein inhalation exposure produced long-lasting potentiation of blood flow responses to a subsequent TRPA1 agonist and sensitized cutaneous responses to mechanical stimulation. C-Fos expression in response to touch was increased in trigeminal nucleus caudalis in animals exposed to acrolein compared with room air. Spontaneous activity in an open-field and scent preference behavior was different in acrolein-exposed compared with room air-exposed animals. Sumatriptan, an acute migraine treatment blocked acute blood flow changes in response to TRPA1 or transient receptor potential vanilloid receptor-1 agonists. Pretreatment with valproic acid, a prophylactic migraine treatment, attenuated the enhanced blood flow responses observed after acrolein inhalation exposures. Environmental irritant exposure yields an animal model of chronic migraine in which to study mechanisms for enhanced headache susceptibility after chemical exposure.

Sex differences in behavioral and neurochemical effects of gonadectomy and aromatase inhibition in rats

Aromatase inhibitors, which are widely used for the treatment of estrogen-dependent cancers, have been associated with psychiatric side effects ranging from mania to depression. In the present study, we investigated sex differences in the behavioral and neurochemical effects of aromatase inhibition on male and female, sham-operated or gonadectomized adult rats. Three weeks after surgery, rats received chronic treatment with the aromatase inhibitor letrozole or vehicle and were then subjected to the open field test, which assesses general activity. Half of the subjects were subsequently exposed to the stressful procedure of the forced swim test (FST), which is also a test of antidepressant activity. Aromatase activity was analyzed in the hypothalamus and testosterone and corticosterone were assayed in the blood serum of all rats. The hippocampus and prefrontal cortex (PFC) were analyzed for monoamine (noradrenaline, dopamine and serotonin), as well as amino acid (GABA, glutamate, glycine, taurine, alanine and histidine) levels. The observed decrease in hypothalamic aromatase activity confirmed the efficacy of letrozole treatment in both sexes. Moreover, letrozole enhanced testosterone levels in sham-operated females. In the open field test, females were overall more active and explorative than males and gonadectomy eliminated this sex difference. In the FST, females exhibited overall higher immobility than males and gonadectomy further enhanced this passive behavior in both sexes. However, sustained aromatase inhibition had no effect on open field and FST behaviors. Head shakes during FST, which were fewer in females than in males, were reduced by castration in males and by letrozole treatment in ovariectomized females, suggesting a role of testosterone and extra-gonadal estrogens in the expression of this behavior. Sustained aromatase inhibition also decreased noradrenaline and the dopaminergic turnover rates [DOPAC/DA, HVA/DA] in the hippocampus and PFC of male and female rats, irrespectively of gonadectomy. Moreover, letrozole treatment enhanced the serotonergic turnover [5HIAA/5HT] rate in the hippocampus of males and females, irrespectively of gonadectomy. Amino acid levels were not influenced by letrozole, but sex differences were demonstrated with higher levels in the PFC of females vs. males. Present findings suggest that the neuropsychiatric effects of aromatase inhibition can be attributed to the inhibition of extragonadal estrogen synthesis, presumably in the brain, and could be further associated with serotonergic and catecholaminergic changes in brain regions involved in mood and cognition. Importantly, present data could be linked with the neurobiology of affective side-effects in post-menopausal women receiving aromatase inhibitors.

Developmental programming of somatic growth, behavior and endocannabinoid metabolism by variation of early postnatal nutrition in a cross-fostering mouse model

BackgroundNutrient deprivation during early development has been associated with the predisposition to metabolic disorders in adulthood. Considering its interaction with metabolism, appetite and behavior, the endocannabinoid (eCB) system represents a promising target of developmental programming.MethodsBy cross-fostering and variation of litter size, early postnatal nutrition of CB6F1-hybrid mice was controlled during the lactation period (3, 6, or 10 pups/mother). After weaning and redistribution at P21, all pups received standard chow ad libitum. Gene expression analyses (liver, visceral fat, hypothalamus) were performed at P50, eCB concentrations were determined in liver and visceral fat. Locomotor activity and social behavior were analyzed by means of computer-assisted videotracking.ResultsBody growth was permanently altered, with differences for length, weight, body mass index and fat mass persisting beyond P100 (all 3>6>10,p<0.01). This was paralleled by differences in hepatic IGF-I expression (p<0.01). Distinct gene expression patterns for key enzymes of the eCB system were observed in fat (eCB-synthesis: 3>6>10 (DAGLα p<0.05; NAPE-PLD p = 0.05)) and liver (eCB-degradation: 3>6>10 (FAAH p<0.05; MGL p<0.01)). Concentrations of endocannabinoids AEA and 2-AG in liver and visceral fat were largely comparable, except for a borderline significance for higher AEA (liver, p = 0.049) in formerly overfed mice and, vice versa, tendencies (p<0.1) towards lower AEA (fat) and 2-AG (liver) in formerly underfed animals. In the arcuate nucleus, formerly underfed mice tended to express more eCB-receptor transcripts (CB1R p<0.05; CB2R p = 0.08) than their overfed fellows. Open-field social behavior testing revealed significant group differences, with formerly underfed mice turning out to be the most sociable animals (p<0.01). Locomotor activity did not differ.ConclusionOur data indicate a developmental plasticity of somatic growth, behavior and parameters of the eCB system, with long-lasting impact of early postnatal nutrition. Developmental programming of the eCB system in metabolically active tissues, as shown here for liver and fat, may play a role in the formation of the adult cardiometabolic risk profile following perinatal malnutrition in humans.

ZL006, a small molecule inhibitor of PSD-95/nNOS interaction, does not induce antidepressant-like effects in two genetically predisposed rat models of depression and control animals

N-methyl-D-aspartate receptor (NMDA-R) antagonists and nitric oxide inhibitors have shown promising efficacy in depression but commonly induce adverse events. To circumvent these, a more indirect disruption of the nitric oxide synthase/postsynaptic density protein 95 kDa complex at the NMDA-R has been proposed. This disruption can be achieved using small molecule inhibitors such as ZL006, which has attracted attention as ischemic stroke therapy in rodents and has been proposed as a potential novel treatment for depression. Based on this, our aim was to translate these findings to animal models of depression to elucidate antidepressant-like properties in more detail. In the present study, we administered ZL006 to two established animal models of depression and control rodents. Following treatment, we measured locomotion in the Open Field and depressive-like behavior in the Forced Swim Test and Tail Suspension Test. Our experimental designs included the use of different species (rats, mice), strains (Flinders Sensitive Line rats, Flinders Resistant Line rats, Wistar Kyoto rats, Wistar Hanover rats, Sprague Dawley rats, B6NTac mice), routes of administration (intraperitoneal, intracerebroventricular), times of administration (single injection, repeated injections), treatment regimens (acute, sustained), and doses (5, 10, 15, 50 mg/kg). ZL006 did not affect behavior in any of the described settings. On a molecular level, ZL006 significantly reduced total nitrate/nitrite concentrations in the cerebellum, supporting that it is capable of reducing nitric oxide metabolites in the brain. Future studies using different experimental parameters are needed to further investigate the behavioral profile of ZL006.

Beta-Adrenergic Blockade Decreases the Neuroimmune Changes in Mice Induced by Cohabitation with an Ehrlich Tumor-Bearing Cage Mate

Objectives: Cohabitation with Ehrlich tumor-bearing (ETB) mice induced behavioral, neurochemical, hormonal, and immune effects in the conspecifics as a consequence of stress-induced activation of the sympathetic nervous system (SNS) with catecholamine release. In the current study, the nonspecific β-AR blocker d,l-propranolol and the specific β₂-AR blocker ICI-118.551 were employed as pharmacological tools to assess the extent to which catecholamines participated in the effects induced by cohabitation with ETB mice. Methods: Two experiments were performed, 1 with d,l-propranolol treatment and the other with ICI-118.551. One mouse in the experimental group was called the “companion of the sick partner” (CSP) since it was forced to live in the same cage with 2 (experiment 1) or 1 (experiment 2) cage mate that had been i.p. injected with 5 × 10⁶ Ehrlich tumor cells. Results: The d,l-propranolol treatment, but not the ICI-118.551 treatment, attenuated the effects of cohabitation with 2 ETB mice on both open-field behavior and the hypothalamic levels and turnover rate of norepinephrine. The 2 β-AR blockers were unable to change the serum corticosterone levels and adrenal weights of the CSP mice; however, these drugs abrogated the effects of cohabitation on neutrophil oxidative burst and phagocytosis. Finally, an increase in the 5-HT turnover rate was observed in the olfactory bulb of CSP mice compared to their respective controls, an effect that was not modified by β-AR blockade. Conclusion: These results confirm and strengthen our hypothesis that the SNS is involved in the effects induced by cohabitation with ETB mice and point towards β₂-AR participation in the immune effects analyzed.

Conservation of Phenotypes in the Roman High- and Low-Avoidance Rat Strains After Embryo Transfer

The Roman high- (RHA-I) and low-avoidance (RLA-I) rat strains are bi-directionally bred for their good versus non-acquisition of two-way active avoidance, respectively. They have recently been re-derived through embryo transfer (ET) to Sprague-Dawley females to generate specific pathogen free (SPF) RHA-I/RLA-I rats. Offspring were phenotyped at generations 1 (G1, born from Sprague-Dawley females), 3 and 5 (G3 and G5, born from RHA-I and RLA-I from G2-G4, respectively), and compared with generation 60 from our non-SPF colony. Phenotyping included two-way avoidance acquisition, context-conditioned fear, open-field behaviour, novelty-seeking, baseline startle, pre-pulse inhibition (PPI) and stress-induced increase in plasma corticosterone concentration. Post-ET between-strain differences in avoidance acquisition, context-conditioned freezing and novelty-induced self-grooming are conserved. Other behavioural traits (i.e. hole-board head-dipping, novel object exploration, open-field activity, startle, PPI) differentiate the strains at G3-G5 but not at G1, suggesting that the pre-/post-natal environment may have influenced these co-segregated traits at G1, though further selection pressure along the subsequent generations (G1-G5) rescues the typical strain-related differences.

Ketamine-induced behavioural and brain oxidative changes in mice: an assessment of possible beneficial effects of zinc as mono- or adjunct therapy.

We studied the influence of zinc, haloperidol or olanzapine on neurobehaviour (open-field, radial arm maze and elevated plus maze) and brain antioxidant status in vehicle- or ketamine-treated mice, with the aim of ascertaining the potentials of zinc in counteracting ketamine's effects. Experiment 1 assessed the effects of zinc in healthy animals and the relative degrees of modulation of ketamine's effects by zinc, haloperidol or olanzapine, respectively. Experiment 2 assessed the modulation of ketamine's effects following co-administration of zinc with haloperidol or olanzapine. Male mice weighing 18-20g each were used. Animals were pretreated with ketamine (except vehicle, zinc, haloperidol and olanzapine controls) for 10days before commencement of 14-day treatment (day 11-24) with vehicle, zinc, haloperidol or olanzapine (alone or in combination). Ketamine injection also continued alongside zinc and/or standard drugs in the ketamine-treated groups. Zinc, haloperidol and olanzapine were administered by gavage. Treatments were given daily and behaviours assessed on days 11 and 24. On day 24, animals were sacrificed and whole brain homogenates used for estimation of glutathione, nitric oxide and malondialdehyde (MDA) levels. Ketamine increased open-field behaviours, nitric oxide and MDA levels, while it decreased working memory, social interaction and glutathione. Administration of zinc alone or in combination with haloperidol or olanzapine was associated with variable degrees of reversal of these effects. Zinc may have the potential of a possible therapeutic agent and/or adjunct in the reversal of schizophrenia-like changes in behaviour and brain oxidative status.

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.

Melatonin attenuates behavioural deficits and reduces brain oxidative stress in a rodent model of schizophrenia

Melatonin is a neurohormone that is linked to the aetiopathogenesis of schizophrenia. The aim of this study was to assess the potentials of oral melatonin supplement in the management of induced schizophrenia-like behavioural and brain oxidative status changes, using an animal model. The relative degrees of modulation of ketamine-induced behaviours by haloperidol, olanzapine or melatonin were assessed in the open-field, Y-maze, elevated plus maze and the social interaction tests. 12-week old, male mice were assigned to six groups of ten each (n=10). They were pretreated with daily intraperitoneal ketamine at 15mg/kg (except vehicle) for 10days, before commencement of 14day treatment with standard drug (haloperidol or olanzapine) or melatonin. Ketamine injection also continued alongside melatonin or standard drugs administration for the duration of treatment. Melatonin, haloperidol and olanzapine were administered by gavage. Treatments were given daily, and behaviours assessed on days 11 and 24. On day 24, animals were sacrificed and whole brain homogenates used for the estimation of glutathione, nitric oxide and malondialdehyde levels. Ketamine injection increased open-field behaviours; while it decreased working-memory, social-interaction and glutathione activity. Nitric oxide and malondialdehyde levels also increased after ketamine injection. Administration of melatonin was associated with variable degrees of reversal of these effects. In conclusion, melatonin may have the potential of a possible therapeutic agent and/or adjunct in the management of schizophrenia.

Association of open field behavior with blood and semen characteristics in roosters: an alternative animal model

IntroductionThe paucity of literature is addressed regarding the correlation between open field as an individual behavioral trait on reproductive capacity in animals. Materials and methodsTo address this, Nine-month-old indigenous roosters were housed in individual cages. Each animal was observed twice a week for ten minutes before feeding in an open field apparatus for two weeks (7:00–12:00PM). ResultsInterestingly, it was found that rooster's semen characteristics were correlated with their open field behavior. On the other hand, plasma glucose level as a blood attribute was more correlated with semen characteristics. The open field monitoring also revealed that the roosters with the lowest delay to their first pace had the highest sperm forward motility and lower sperm abnormality. The heterophil to lymphocyte ratio (H:L) was found to be low when pace bout and pace numbers were 20 and 35, respectively. The negative correlation between H:L ratio and semen characteristics (live sperm percentage, sperm concentration, and membrane integrity) may be an indication of poor reproductive performance in fearful roosters with higher H:L ratio. ConclusionsThe data suggested a relationship between open field behavior indices and some reproductive parameters in roosters. The results might be applicable for selection of more reproductive animals. Hence, the rooster may also be useful model for similar studies in other species.

Postnatal LPS Challenge Impacts Escape Learning and Expression of Plasticity Factors Mmp9 and Timp1 in Rats: Effects of Repeated Training

Bacterial intoxication associated with inflammatory conditions during development can impair brain functions, in particular evolutionarily novel forms of memory, such as explicit learning. Little is known about the dangers of early-life inflammation on more basic forms of learning, for example, the acquisition of motor escape abilities, which are generally better preserved under pathological conditions. To address this limitation in knowledge, an inflammatory response was elicited in Wistar pups by lipopolysaccharide (LPS) injections (25 μg/kg) on postnatal days P15, P18 and P21. The acquisition of escape behaviour was tested from P77 by active avoidance footshock model and water maze. Open-field behaviour and blood corticosterone levels were also measured. Rat brain tissue was collected from pups 2 h post-injection and from adult rats which either underwent escape training on P77–P81 or remained untrained. mRNA levels of developmental brain plasticity factors MMP-9 and TIMP-1 were investigated in the medial prefrontal cortex and ventral/dorsal hippocampus. LPS-challenged rats displayed moderately deficient escape responses in both memory tests, increased freezing behaviour and, surprisingly, reduced blood cortisol levels. Mmp9 and Timp1, and their ratio to one another, were differentially altered in pups versus adult untrained rats but remained unchanged overall in rats trained in either learning task. Together, our data indicate that systemic pro-inflammatory response during early postnatal development has long-lasting effects, including on the acquisition of motor escape abilities and plasticity factor expression, into adulthood. Our data suggest that altered stress response could possibly mediate these deviations and repeated training might generate positive effects on plasticity under the employed conditions.

Subchronic Amitriptyline Influences Open-field Behaviours and Spontaneous Working-memory in Healthy Mice

Objective: We assessed the effects of amitriptyline on open-field locomotion, stereotypic behaviours and spatial working-memory in healthy mice. Method: Five groups of mice were administered vehicle (distilled water), scopolamine (2 mg/kg), or one of three doses of amitriptyline (5, 10 and 15 mg/kg) for 21 days. Behaviours were assessed after the first and final dose of treatment. Result: Administration of the first dose of amitriptyline was associated with enhanced open-field horizontal locomotion, rearing and grooming; with repeated administration, there was suppression of horizontal locomotion and rearing. A dose-related decrease in Y-maze and radial-arm maze spatial working-memory was also observed after repeated administration. Compared to scopolamine, amitriptyline was associated with a significant reduction in open-field behaviours, but a significantly-higher spatial working-memory score. Conclusion: Repeated administration of amitriptyline in healthy mice was associated with suppression of locomotion and grooming; working-memory deficits were also observed. However, working-memory task performance is significantly better than the scopolamine group.

Monosodium glutamate-associated alterations in open field, anxiety-related and conditioned place preference behaviours in mice.

The present study investigated changes in behaviour associated with oral monosodium glutamate (a flavouring agent), using the open field, elevated plus maze and conditioned place preference (CPP) paradigms, respectively. Mice were assigned to two groups for CPP [monosodium glutamate (MSG)-naïve (n=40) and MSG-pretreated (n=40)] and two groups for open field (OF) and elevated plus maze (EPM) tests [n=40 each], respectively. Animals in respective groups were then divided into four subgroups (n=10) (vehicle or MSG (80, 160 and 320mg/kg)). MSG-naïve mice were observed in the CPP box in three phases (pre-conditioning, conditioning and post-conditioning). Mice were conditioned to MSG or an equivalent volume of saline. The MSG pretreatment group received vehicle or respective doses of MSG daily for 21days, prior to conditioning. Mice in the OF or EPM groups received vehicle or doses of MSG (orally) for 21days, at 10ml/kg. Open field or EPM behaviours were assessed on days 1 and 21. At the end of the experiments, mice in the OF groups were sacrificed and brain homogenates used to assay glutamate and glutamine. Results showed that administration of MSG was associated with a decrease in rearing, dose-related mixed horizontal locomotor, grooming and anxiety-related response and an increase in brain glutamate/glutamine levels. Following exposure to the CPP paradigm, MSG-naïve and MSG-pretreated mice both showed 'drug-paired' chamber preference. The study concluded that MSG (at the administered doses) was associated with changes in open field activities, anxiety-related behaviours and brain glutamate/glutamine levels; its ingestion also probably leads to a stimulation of the brain reward system.

Sex Differences in the Physiological and Behavioral Effects of Chronic Oral Methylphenidate Treatment in Rats.

Methylphenidate (MP) is a psychostimulant prescribed for Attention Deficit Hyperactivity Disorder. Previously, we developed a dual bottle 8-h-limited-access-drinking-paradigm for oral MP treatment of rats that mimics the pharmacokinetic profile of treated patients. This study assessed sex differences in response to this treatment. Male and female Sprague Dawley rats were assigned to one of three treatment groups at 4 weeks of age (n = 12/group): Control (water), low dose (LD) MP, and high dose (HD) MP. Rats drank 4 mg/kg MP (LD) or 30 mg/kg MP (HD) during the first hour, and 10 mg/kg (LD) or 60 mg/kg MP (HD) for the remaining 7 h each day. Throughout 3 months of treatment, rats were monitored for body weight, food intake, and fluid intake; as well as tested for open field behavior, circadian activity, novel object recognition, and social interaction. Chronic MP treated rats exhibited reduced fluid intake during distinct treatment weeks to a greater extent in males, and reduced total fluid intake in males only. HD MP treatment decreased body weight in both sexes, while HD MP increased total food intake in females only, likely to offset energy deficits resulting from MP-induced hyperactivity. LD and HD MP increased locomotor activity in the open field, particularly in females and during later treatment weeks. MP dose-dependently increased activity during the dark cycle of circadian testing in females, while in males hyperactivity was only exhibited by HD rats. HD MP increased center activity to a greater extent in males, while MP increased rearing behavior in females only. MP had no effect on social behavior or novel object recognition in either sex. This study concludes that chronic oral MP treatment at clinically-relevant dosages has significant effects on food intake, body weight, open field behavior, and wake cycle activity. Particularly marked sex differences were apparent for locomotor activity, with females being significantly more sensitive to the hyperactivating effects of the drug. These findings suggest that chronic MP exposure beginning in adolescence can have significant behavioral effects that are both dose- and sex-dependent, and raise concerns regarding the reversibility of these effects post-discontinuation of treatment.

Upregulation of Mineralocorticoid Receptor in the Hypothalamus Associated with a High Anxiety-like Level in Apolipoprotein E4 Transgenic Mice.

Anxiety symptoms occur in a large portion of Alzheimer's disease (AD) patients. ApolipoproteinE-4 (ApoE ε4 allele), a risk factor for AD, has been recognized as an important contributor to psychiatric disorders. In the present study, we aimed to investigate the corticosterone level in relation to anxiety-like behavior changes in transgenic male mice with different glial fibrillary acidic protein (GFAP)-ApoE isoforms. GFAP-ApoE4 transgenic mice aged 3months showed higher anxiety-like behavior in open field, light-dark box and elevated plus maze tasks compared with that of age-matched GFAP-ApoE3 mice. However, corticotropin releasing factor levels in the hypothalamus and plasma corticosterone secretion were similar in GFAP-ApoE3 and GFAP-ApoE4 transgenic male mice. Additionally, increased expression of the mineralocorticoid receptor (MR) and unchanged expression of the glucocorticoid receptor were observed in the hypothalamus of GFAP-ApoE4 mice. However, no significant differences were found in the expression levels of the MR in GFAP-ApoE3 and GFAP-ApoE4 mice at postnatal day 2. In conclusion, we found that MR upregulation rather than corticosterone level changes in the early stage of adulthood was associated with the higher anxiety-like level measured in GFAP-ApoE4 mice.

Acute ethanol exposure during late mouse neurodevelopment results in long-term deficits in memory retrieval, but not in social responsiveness.

ObjectivePrenatal alcohol exposure can result in neurological changes in affected individuals and may result in the emergence of a broad spectrum of neurobehavioral abnormalities termed fetal alcohol spectrum disorders (FASD). The effects of ethanol exposure during development are both time and dose dependent. Although many animal models of FASD use more chronic ethanol exposure, acute developmental alcohol exposure may also cause long‐lasting neuronal changes. Our research employed behavioral measures to assess the effects of a single early postnatal ethanol intoxication event in mice.Materials and MethodsMice were dosed at postnatal day 6 (a 2.5 g/kg dose of ethanol or a saline control administered twice, 2 hr apart) as a model of third trimester binge drinking in humans. This exposure was followed by behavioral assessment in male mice at 1 month (1M) and at 4 months of age (4M), using the Barnes maze (for learning/memory retrieval), exploratory behavior, and a social responsiveness task.ResultsEthanol‐exposed mice appeared to be less motivated to complete the Barnes maze at 1M, but were able to successfully learn the maze. However, deficits in long‐term spatial memory retrieval were observed in ethanol‐exposed mice when the Barnes maze recall was measured at 4M. No significant differences were found in open field behavior or social responsiveness at 1M or 4M of age.ConclusionsAcute ethanol exposure at P6 in mice leads to mild but long‐lasting deficits in long‐term spatial memory. Results suggest that even brief acute exposure to high ethanol levels during the third trimester equivalent of human pregnancy may have a permanent negative impact on the neurological functioning of the offspring.

Otolith dysfunction alters exploratory movement in mice

The organization of rodent exploratory behavior appears to depend on self-movement cue processing. As of yet, however, no studies have directly examined the vestibular system’s contribution to the organization of exploratory movement. The current study sequentially segmented open field behavior into progressions and stops in order to characterize differences in movement organization between control and otoconia-deficient tilted mice under conditions with and without access to visual cues. Under completely dark conditions, tilted mice exhibited similar distance traveled and stop times overall, but had significantly more circuitous progressions, larger changes in heading between progressions, and less stable clustering of home bases, relative to control mice. In light conditions, control and tilted mice were similar on all measures except for the change in heading between progressions. This pattern of results is consistent with otoconia-deficient tilted mice using visual cues to compensate for impaired self-movement cue processing. This work provides the first empirical evidence that signals from the otolithic organs mediate the organization of exploratory behavior, based on a novel assessment of spatial orientation.

Maternal fluoride exposure during gestation and lactation decreased learning and memory ability, and glutamate receptor mRNA expressions of mouse pups.

Previous investigations demonstrated that high fluoride (F) exposure may adversely affect the neurodevelopment and learning and memory ability. However, whether maternal F exposure during gestation and lactation can influence the learning, memory ability, and glutamate receptor expressions of offspring has not yet been elucidated. Hence, in the present study, maternal mice were exposed to F (25, 50, or 100 mg/L sodium fluoride (NaF) in drinking water) during gestation and lactation. Results showed that exposure to 100 mg/L NaF significantly enhanced the number of total arm entries and working memory errors of offspring in the radial arm maze test compared to the control group. However, no difference was observed in open-field behaviors. For the subtypes of glutamate receptors in hippocampus, expression of GluR2 mRNA was significantly reduced by 25, 50, and 100 mg/L NaF. Besides, F exposure also suppressed the expression of NR2A, NR2B, and mGluR2 mRNA levels in a dose-dependent manner, where NR2A was significantly suppressed by 50 mg/L NaF and NR2B and mGluR2 by 100 mg/L NaF. However, no significant changes were observed in GluR1 and mGluR5 mRNA expression levels. Collectively, these findings suggested that F can pass through the cord blood and breast milk and may have deleterious impact on learning and memory of the mouse pups, which was mediated by reduced mRNA expression of glutamate receptor subunits.