Antidepressant effect of PT-31, an α2-adrenoceptor agonist, on lipopolysaccharide-induced depressive-like behavior in mice.

Increasing evidence indicates that neuroinflammation, oxidative stress, and neurotrophic factors play a key role in the pathophysiology of major depressive disorder (MDD). In addition, the attenuation of inflammatory response has been considered a putative mechanism for MDD treatment. PT-31 is an imidazolidine derivative and a putative α2-adrenoceptor agonist that has previously demonstrated antinociceptive activity. The present study aimed to investigate the effect of PT-31 on depressive-like behavior and lipopolysaccharide-induced neurochemical changes. To this end, mice received intraperitoneally saline or lipopolysaccharide (600 µg/kg), and 5 h postinjection animals were orally treated with saline, PT-31 (3, 10, and 30 mg/kg), or fluoxetine (30 mg/kg). Mice were subjected to the open field test (OFT) 6 and 24 h after lipopolysaccharide administration and to the tail suspension test (TST) 24 h postlipopolysaccharide. Subsequently, animals were euthanized, and brains were dissected for neurochemical analyses. The administration of lipopolysaccharide-induced sickness- and depressive-like behaviors, besides promoting an increase in myeloperoxidase activity and a reduction in brain-derived neurotrophic factor (BDNF) levels. Noteworthy, PT-31 3 mg/kg attenuated lipopolysaccharide-induced decreased locomotor activity 6 h after lipopolysaccharide in the OFT. All tested doses of PT-31 significantly reduced the immobility time of animals in the TST and attenuated lipopolysaccharide-induced increased myeloperoxidase activity in the cortex of mice. Our results demonstrate that PT-31 ameliorates behavioral changes promoted by lipopolysaccharide in OFT and TST, which is possibly mediated by attenuation of the inflammatory response.

New insights about the antidepressant-like effects of riparin A in a chronic murine model of depression.

Riparin A is a synthetic form of natural riparins. Acute scale studies that take into consideration the structure-activity relationship have shown preliminary evidence of antidepressant and anxiolytic effects of riparin A, similar to that already known for other riparins. However, for better pharmacological characterization of this new compound, further studies are required. The aim of this work was to evaluate the effect of chronic treatment with riparin A (10 mg/kg; intraperitoneally) on depressive-like behavior in the forced swimming test and tail suspension test, as well as the reduction of anhedonia in the sucrose preference test, and on anxiety-like behavior in the open field and elevated plus maze apparatus, triggered in rats previously subjected to unpredictable chronic mild stress by 4 weeks. In addition, a pentobarbital-induced sleep time test was also used. Riparin A reduced the duration of immobility in both the forced swimming test and tail suspension test, as well as attenuated the anhedonia in the sucrose preference test. Furthermore, riparin A appears to produce anxiolytic effects in rats exposed to an open field and elevated plus maze, while increasing the alertness/vigilance in rats submitted to pentobarbital-induced sleep time test, without altering their locomotor integrity. Our results suggest that chronic riparin A appears to be a potential pharmacological target for new studies on the control of depression- and anxiety-like behaviors in stressed rats.

Inhibition of Extracellular Signal-Regulated Kinase Activity Improves Cognitive Function in Mice Subjected to Myocardial Infarction.

Cognitive impairment is a commonly observed complication following myocardial infarction; however, the underlying mechanisms are still not well understood. The most recent research suggests that extracellular signal-regulated kinase (ERK) plays a critical role in the development and occurrence of cognitive dysfunction-related diseases. This study aims to explore whether the ERK inhibitor U0126 targets the ERK/Signal Transducer and Activator of Transcription 1 (STAT1) pathway to ameliorate cognitive impairment after myocardial infarction. To establish a mouse model of myocardial infarction, we utilized various techniques including Echocardiography, Hematoxylin-eosin (HE) staining, Elisa, Open field test, Elevated plus maze test, and Western blot analysis to assess mouse cardiac function, cognitive function, and signal transduction pathways. For further investigation into the mechanisms of cognitive function and signal transduction, we administered the ERK inhibitor U0126 via intraperitoneal injection. Reduced total distance and activity range were observed in mice subjected to myocardial infarction during the open field test, along with decreased exploration of the open arms in the elevated plus maze test. However, U0126 treatment exhibited a significant improvement in cognitive decline, indicating a protective effect through the inhibition of the ERK/STAT1 signaling pathway. Hence, this study highlights the involvement of the ERK/STAT1 pathway in regulating cognitive dysfunction following myocardial infarction and establishes U0126 as a promising therapeutic target.

Investigating Morphological Changes of the Hippocampus After Prolonged Aerobic Exercise in Mice: Neural Function and Learning Capabilities / Investigación de los Cambios Morfológicos del Hipocampo Después De un Ejercicio Aeróbico Prolongado en Ratones: Función Neuronal y Capacidades de Aprendizaje

SUMMARY: Both the academic and popular worlds have paid close attention to the link between exercise and cognitive performance. It is increasingly important to understand the numerous mechanisms by which exercise might influence cognitive abilities in view of the continuous societal issues caused by aging populations and the prevalence of disorders associated to cognitive decline. A rising amount of evidence showing a favorable association between physical activity and cognitive well-being serves as the foundation for the justification for studying the effects of exercise on cognitive function and learning ability. The study employed an 8-week treadmill based on exercise on male adults C57BL/6 mice. The exercise group were engaged in 5 sessions a week gradually increasing the intensity of the protocol by 5 % each week. The Mice cognitive assessments were done using Morris Water Maze and Novel Object Recognition tests. The long term-impact on learning ability were further assessed through immmohistochemistry and molecular analysis of the hippocampal and prefrontal cortex tissues of the animals' brain tissues. The findings showed improved spatial learning abilities, recognition memory, and heighted synaptic plasticity indicated by elevated synaptic makers. The study underscores the role of long-term aerobic exercise in augmenting cognitive performance. It not only contributes to the understanding of the interplay between neuroplasticity and cognitive benefits but also the growing body of research on the impact of exercise on cognitive function.

Tanto el mundo académico como el popular han prestado mucha atención al vínculo entre el ejercicio y el rendimiento cognitivo. Es cada vez más importante comprender los numerosos mecanismos por los cuales el ejercicio podría influir en las capacidades cognitivas en vista de los continuos problemas sociales causados por el envejecimiento de la población y la prevalencia de trastornos asociados al deterioro cognitivo. Una cantidad cada vez mayor de evidencia que muestra una asociación favorable entre la actividad física y el bienestar cognitivo sirve como base para justificar el estudio de los efectos del ejercicio sobre la función cognitiva y la capacidad de aprendizaje. El estudio se realizó en ratones machos adultos C57BL/6 utilizándose en los ejercicios una cinta rodante durante 8 semanas. El grupo de ejercicio realizó 5 sesiones por semana aumentando gradualmente la intensidad del protocolo en un 5 % cada semana. Las evaluaciones cognitivas de los ratones se realizaron utilizando las pruebas Morris Water Maze y Novel Object Recognition. El impacto a largo plazo en la capacidad de aprendizaje se evaluó mediante inmunohistoquímica y análisis molecular de los tejidos del hipocampo y la corteza prefrontal de los tejidos cerebrales de los animales. Los hallazgos mostraron mejoras en las habilidades de aprendizaje espacial, la memoria de reconocimiento y una mayor plasticidad sináptica indicada por unos creadores sinápticos elevados. El estudio subraya el papel del ejercicio aeróbico a largo plazo para aumentar el rendimiento cognitivo. No sólo contribuye a la comprensión de la interacción entre la neuroplasticidad y los beneficios cognitivos, sino también al creciente conjunto de investigaciones sobre el impacto del ejercicio en la función cognitiva.

Environmental enrichment enhances the antidepressant effect of ketamine and ameliorates spatial memory deficits in adult rats.

Ketamine is a rapid-acting antidepressant associated with various cognitive side effects. To mitigate these side effects while enhancing efficacy, it can be co-administered with other antidepressants. In our study, we adopted a similar strategy by combining ketamine with environmental enrichment, a potent sensory-motor paradigm, in adult male Wistar rats. We divided the animals into four groups based on a combination of housing conditions and ketamine versus vehicle injections. The groups included those housed in standard cages or an enriched environment for 50 days, which encompassed a 13-day-long behavioral testing period. Each group received either two doses of ketamine (20 mg/kg, IP) or saline as a vehicle. We tested the animals in the novel object recognition test (NORT), forced swim test (FST), open field test (OFT), elevated plus maze (EPM), and Morris water maze (MWM), which was followed by ex vivo c-Fos immunohistochemistry. We observed that combining environmental enrichment with ketamine led to a synergistic antidepressant effect. Environmental enrichment also ameliorated the spatial memory deficits caused by ketamine in the MWM. There was enhanced neuronal activity in the habenula of the enrichment only group following the probe trial of the MWM. In contrast, no differential activity was observed in enriched animals that received ketamine injections. The present study showed how environmental enrichment can enhance the antidepressant properties of ketamine while reducing some of its side effects, highlighting the potential of combining pharmacological and sensory-motor manipulations in the treatment of mood disorders.

Differential impact of intermittent versus continuous treatment with clozapine on fatty acid metabolism in the brain of an MK-801-induced mouse model of schizophrenia.

Continuous antipsychotic treatment is often recommended to prevent relapse in schizophrenia. However, the efficacy of antipsychotic treatment appears to diminish in patients with relapsed schizophrenia and the underlying mechanisms are still unknown. Moreover, though the findings are inconclusive, several recent studies suggest that intermittent versus continuous treatment may not significantly differ in recurrence risk and therapeutic efficacy but potentially reduce the drug dose and side effects. Notably, disturbances in fatty acid (FA) metabolism are linked to the onset/relapse of schizophrenia, and patients with multi-episode schizophrenia have been reported to have reduced FA biosynthesis. We thus utilized an MK-801-induced animal model of schizophrenia to evaluate whether two treatment strategies of clozapine would affect drug response and FA metabolism differently in the brain. Schizophrenia-related behaviors were assessed through open field test (OFT) and prepulse inhibition (PPI) test, and FA profiles of prefrontal cortex (PFC) and hippocampus were analyzed by gas chromatography-mass spectrometry. Additionally, we measured gene expression levels of enzymes involved in FA synthesis. Both intermittent and continuous clozapine treatment reversed hypermotion and deficits in PPI in mice. Continuous treatment decreased total polyunsaturated fatty acids (PUFAs), saturated fatty acids (SFAs) and FAs in the PFC, whereas the intermittent administration increased n-6 PUFAs, SFAs and FAs compared to continuous administration. Meanwhile, continuous treatment reduced the expression of Fads1 and Elovl2, while intermittent treatment significantly upregulated them. This study discloses the novel findings that there was no significant difference in clozapine efficacy between continuous and intermittent administration, but intermittent treatment showed certain protective effects on phospholipid metabolism in the PFC.

The Impact of C-3 Side Chain Modifications on Kynurenic Acid: A Behavioral Analysis of Its Analogs in the Motor Domain.

The central nervous system (CNS) is the final frontier in drug delivery because of the blood-brain barrier (BBB), which poses significant barriers to the access of most drugs to their targets. Kynurenic acid (KYNA), a tryptophan (Trp) metabolite, plays an important role in behavioral functions, and abnormal KYNA levels have been observed in neuropsychiatric conditions. The current challenge lies in delivering KYNA to the CNS owing to its polar side chain. Recently, C-3 side chain-modified KYNA analogs have been shown to cross the BBB; however, it is unclear whether they retain the biological functions of the parent molecule. This study examined the impact of KYNA analogs, specifically, SZR-72, SZR-104, and the newly developed SZRG-21, on behavior. The analogs were administered intracerebroventricularly (i.c.v.), and their effects on the motor domain were compared with those of KYNA. Specifically, open-field (OF) and rotarod (RR) tests were employed to assess motor activity and skills. SZR-104 increased horizontal exploratory activity in the OF test at a dose of 0.04 µmol/4 µL, while SZR-72 decreased vertical activity at doses of 0.04 and 0.1 µmol/4 µL. In the RR test, however, neither KYNA nor its analogs showed any significant differences in motor skills at either dose. Side chain modification affects affective motor performance and exploratory behavior, as the results show for the first time. In this study, we showed that KYNA analogs alter emotional components such as motor-associated curiosity and emotions. Consequently, drug design necessitates the development of precise strategies to traverse the BBB while paying close attention to modifications in their effects on behavior.

Glycitein prevents reserpine-induced depression and associated comorbidities in mice: modulation of lipid peroxidation and TNF-α levels.

Depression is a debilitating mood disorder affecting millions worldwide and continues to pose a significant global health burden. Due to the multifaceted nature of depression, the current treatment regimens are not up to mark in terms of their multitargeting potential and least side effect profile. Molecules within the isoflavone class demonstrate promising potential in alleviating depression and associated conditions, offering a multifaceted approach to manage mental health concerns. Therefore, the current study was designed to explore the potential of glycitein, an isoflavone in managing reserpine-induced depression and associated comorbidities in mice. Reserpine (0.5 mg/kg; i.p.) administration for the first 3 days induced depression and associated comorbidities as evidenced by increased immobility time in forced swim test (FST) and tail suspension test (TST), along with reduced locomotor activity in the open field test (OFT) and increased latency to reach the platform in the Morris water maze (MWM) test. Reserpine treatment also upregulated and downregulated the brain thiobarbituric acid reactive substance (TBARS) and glutathione (GSH) levels, respectively. Furthermore, reserpine administration also uplifted the level of TNF-α in the serum samples. Glycitein (3 mg/kg and 6 mg/kg; p.o.) treatment for 5 days prevented the depressive effect of reserpine. It also improved the spatial memory at both dose levels. Moreover, in biochemical analysis, glycitein also reduced the brain TBARS and serum tumor necrosis factor-alpha (TNF-α) levels. Whereas, no significant effect was seen on the brain GSH level. Glycitein (6 mg/kg) was found to be more effective than the 3 mg/kg dose of glycitein. Overall results delineate that glycitein has the potential to manage depression and impaired memory by inhibiting lipid peroxidation and inflammatory stress.

HDAC2 Inhibits Hippocampal Neurogenesis and Impairs the Cognitive Function in Prenatally Stressed Adult Offspring / HDAC2 Inhibe la Neurogénesis del Hipocampo y Afecta la Función Cognitiva en la Descendencia Adulta Estresada Prenatalmente

SUMMARY: The objective of this study was to investigate the mechanism of prenatal stress on the cognitive function of offspring, and clarify the change of histone deacetylase 2 (HDAC2) expression in hippocampal neurons of offspring. 16 pregnant SD rats were randomly divided into control group and stress group, with eight rats in each group. The stress group received restrained stress from 15 to 21 days of pregnancy, while the control group did not receive any treatment. Anxiety-like behavior and spatial memory, learning and memory ability were detected in open field, elevated plus maze, novel object recognition test, and Barnes maze. Nissl staining was used to detect the function of hippocampal neurons. Western blot was used to detect the expression of HDAC2 protein in hippocampal neurons of adult offspring. Immunofluorescence staining was used to detect the expression of HDAC2 protein and hippocampal neurogenesis. The learning and memory ability of adult offspring was decreased. The prenatal stress damaged the function of hippocampal neurons , the expression of HDAC2 was down-regulated, and the number of neurons was reduced. Maternal prenatal stress can down- regulate the expression of HDAC2 in the hippocampus of offspring, inhibits hippocampal neurogenesis and impairs the cognitive function.

El objetivo de este estudio fue investigar el mecanismo del estrés prenatal en la función cognitiva de la descendencia y aclarar el cambio de la expresión de la histona desacetilasa 2 (HDAC2) en las neuronas del hipocampo de la descendencia. 16 ratas SD preñadas se dividieron aleatoriamente en un grupo de control y un grupo de estrés, con ocho ratas en cada grupo. El grupo de estrés recibió estrés durante 15 a 21 días de pre, preñez, mientras que el grupo de control no recibió ningún tratamiento. El comportamiento similar a la ansiedad y la memoria espacial, el aprendizaje y la capacidad de memoria se detectaron en campo abierto, laberinto en cruz elevado, prueba de reconocimiento de objetos novedosos y laberinto de Barnes. La tinción de Nissl se utilizó para detectar la función de las neuronas del hipocampo. Se utilizó Western blot para detectar la expresión de la proteína HDAC2 en las neuronas del hipocampo de la descendencia adulta. La tinción de inmunofluorescencia se utilizó para detectar la expresión de la proteína HDAC2 y la neurogénesis del hipocampo. La capacidad de aprendizaje y memoria de la descendencia adulta se redujo. El estrés prenatal dañó la función de las neuronas del hipocampo, se reguló negativamente la expresión de HDAC2 y se redujo el número de neuronas. El estrés prenatal materno puede regular a la baja la expresión de HDAC2 en el hipocampo de la descendencia, inhibe la neurogénesis del hipocampo y deteriora la función cognitiva.

Neurobehavioral assessment of Danio reriointoxicated by Mercury and the use of Mercurius solubilis

Mercury is used in various industrial. Part of Mercury's industrial waste is discharged into the environment, rivers and their tributaries, thus contaminating aquatic animals. Aim:to evaluate Mercury-induced behavioral changes in Zebrafish (Danio rerio) by the analysis of locomotor activity and parameters related to neurotoxicity and to verify whether ultra-diluted substances can decrease neurobehavioral effects and toxic. Methodology:The fishes were separated into 4 monitoring aquariums with 8 fishes each, with temperature, pH controlled, until the time of the toxicological experiments. 0.5 mL of Mercury 6cH, 30cH and distilled water (positive control) were added per liter of water in each aquarium containing 6 liters of water, then 3 mL of medication per aquarium, the white control received no medication and the toxic agent. After 1 hour the drugs were added, toxic mercury (200 µg/L), 4 mL per aquarium was added and remained so for 24 hours. All the experiment was run in blind, and the drugs identified by codes. The animals were subjected to behavioral tests (Open Field-locomotion; Vertical Open Field for neurotoxicity evaluation and Light and Dark Test), and each stage was recorded for later evaluation of movements and neurobehavioral changes. ANOVA was performed, followed by Tukey test, with p <0.05. Results: Mercury produced an anxiogenic effect in animals that were submitted to it without medication. In the vertical open field, there was an increase in erratic movements (1.25 ± 1.0) and tremors (0.87 ± 0.35) compared to the control (0.12 ± 0.35 and 0.25 ± 0.46 respectively), proving the toxic effect. Fishes which received the medication at 6 cH and 30 ch showed tremors and erratic movements similar to control. Conclusion:200 µg/L mercury in water can cause neurobehavioral disturbances in fishes, and animals receiving Mercurius6 cH and 30 cH ultra-diluted drug did not show neurotoxicity.

Antidepressant-like effect of caffeic acid: Involvement of the cellular signaling pathways

Abstract Caffeic acid is a phenolic compound widely distributed in plants and beverages such as coffee. Although its mechanism of action is poorly understood, caffeic acid reportedly induces antidepressant-like and neuroprotective effects. This study aimed to investigate the involvement of cellular signaling pathways in acute antidepressant-like effect induced by caffeic acid in mice. All procedures were approved by the Institutional Animal Ethics Committee of the UNIVALI n. 021/2013. Female Swiss mice were administered with vehicle, caffeic acid (5 mg/ kg, p.o.), inhibitor (H-89, U0126, chelerythrine, or PD9859, i.c.v.) or caffeic acid plus inhibitor. The behavioral effects were evaluated 1h after the administration of compounds to mice using tail suspension test (TST) and open field test (OFT). The results showed that the antidepressant- like effect of caffeic acid in mice was possibly mediated by the activation of PKA, MEK 1/2, PKC and MAPK (as assessed using TST), without compromising their locomotor activity (as assessed using OFT). Our results demonstrated, at least in part, the pathways involved in the neuroprotective and behavioral effects of caffeic acid.

Behavioral characterization of ayahuasca treatment on Wistar rats in the open field test

Abstract Ayahuasca (AYA) is a psychedelic beverage with therapeutic potential for many mood and anxiety disorders. Although there are some preclinical studies, no published reports have tested the behavioral effects of AYA gavage in animal models. This investigation aimed to characterize the behavior of Wistar rats after acute ingestion of AYA for 40 min in the open field test (OFT). The sample consisted of three experimental groups treated with different dosages of AYA (125, 250, or 500 mg kg-1) and a control group. Each group consisted of 10 participants. After gavage, the number of crossings of the OFT grid lines, latency to enter the central area of the device, grooming frequency, and time spent in the central perimeter of the device were immediately evaluated. Analyses were based on one-way ANOVA and a linear-regression mixture model for longitudinal data. AYA intake did not interfere with habituation. The 500 mg kg-1 group showed a decrease in the time spent in the center of the device and in the number of crossings compared to the control group in the last 10 min. These results suggest that gavage with AYA did not interfere with the results, and the behavioral effects were perceived only between 30 and 40 min after gavage. Taken together, the results indicate that three aspects should be considered in OFT studies of AYA acute effects: the moment when the observation starts, the observation period, and the AYA dosage.

Evaluation of subchronic formaldehyde exposure in rats with open field test / Evaluación de la exposición al formaldehído subcrónico en ratas con prueba de campo abierto

SUMMARY: Formaldehyde (FA), which is an indispensable chemical substance in anatomy and pathology, is a very harmful substance for living things. In our study, the purpose was to investigate the changes in behavior of rats exposed to subchronic formaldehyde with open field test. We divided 24 Wistar-Albino rats into 3 groups. The first group (n=8) was identified as the control group, and normal air breathing was ensured. Low-dose FA (mean 1 ppm) was inhaled in the second group, and high-dose FA (mean 10 ppm) was inhaled in the third group. FA exposure was done for 4 hours, 12 weeks, and 5 days a week. The rats were subjected to open field test during the first week and the last week of FA exposure. We observed significant decreases in the number of vertical movements and grooming in rats in the experimental group compared to the control group in the open field test (p 0.05). As a conclusion, we can argue that FA causes changes in the behaviors of rats regardless of dose and duration.

RESUMEN: El formaldehído (FA), una sustancia química indispensable en la anatomía y patología, pero es un elemento sumamente nocivo para todos los seres vivos., El objetivo de nuestro estudio fue investigar los cambios en el comportamiento de ratas expuestas a formaldehído subcrónico con prueba de campo abierto. Utilizamos 24 ratas Wistar-Albino divididas en 3 grupos. El primer grupo (n = 8) se identificó como el grupo de control y se aseguró una respiración normal de aire. En el segundo grupo se inhalaron dosis bajas de FA (media de 1 ppm) y en el tercer grupo se inhalaron dosis altas de FA (media de 10 ppm). La exposición a FA se realizó durante 4 horas, 12 semanas y 5 días a la semana. Las ratas fueron sometidas a una prueba de campo abierto durante la primera semana y la última semana de exposición a FA. Observamos disminuciones significativas en el número de movimientos verticales y acicalamiento en ratas en el grupo experimental en comparación con el grupo control en la prueba de campo abierto (p 0,05). Como conclusión, podemos argumentar que la AF provoca cambios en el comportamiento de las ratas independientemente de la dosis y la duración.

Efeitos do enriquecimento ambiental sobre padrões de comportamento e ansiedade no Status Epilepticus / Effects of environmental enrichment on behavioral and anxiety no Status Epilepticus

Introdução: O Enriquecimento ambiental (EA) tem sido estudado em reabilitação para diversas patologias. Objetivo: investigar os efeitos do EA em ratos wistar jovens submetidos ao status epilepticus, sobre os padrões de comportamento e ansiedade. Métodos: Estudo longitudinal com 40 ratos, submetidos às crises no 15º dia e enriquecimento ambiental e, posteriormente, aos testes labirinto em cruz elevado e campo aberto. Utilizou-se o teste ANOVA two-way, considerando como significante valor de p<0,05. Resultados: No teste do labirinto houve relação entre levantar em duas patas (p<0,01), comportamento de risco (p<0,01) tempo nos braços abertos (p<0,01), número de entradas nos braços fechados (p<0,01), tempo nos braços fechados (p<0,01) e o número de cruzamentos no campo aberto (p=0,01) com status epilepticus. Não houve relação entre os testes e o EA. Conclusão: O EA não reverteu os padrões de ansiedade e comportamento afetados pelo status epilepticus. (AU)

Background: Environmental Enrichment (EE) has been studied in rehabilitation for several pathologies. Objective: to investigate the effects of EE on young wistar rats submitted to status epilepticus, on behavior and anxiety patterns. Methods: Longitudinal study with 40 rats, submitted to seizures on the 15th day and environmental enrichment, and later to the labyrinth tests in high cross and open field. The two-way ANOVA test was used, considering a significant value of p <0.05. Results: In the labyrinth test, there was a relationship between two paws (p <0.01), risk behavior (p <0.01) in open arms (p <0.01), number of entries in closed arms (p <0.01), time in the closed arms (p <0.01) and the number of crosses in the open field (p = 0.01) with status epilepticus. There was no relationship between the tests and the EE. Conclusion: The EE did not reverse the behavior and anxiety patterns affected by the status epilepticus. (AU)