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Acute seizures can severely affect brain function and development. However, the underlying pathophysiological mechanisms are still poorly understood. Disturbances of the glutamatergic system are considered one of the critical mechanisms of neurological abnormalities. In the present study, we analyzed changes in the expression of NMDA and AMPA receptor subunits in the different brain regions (dorsal hippocampus, amygdala, and the medial prefrontal, temporal, and entorhinal cortex) using a pentylenetetrazole (PTZ) model of seizures in 3-week-old rats. A distinctive feature of this model is that the administration of PTZ causes severe acute seizures, which are not followed by the development of spontaneous recurrent seizures later on. Subunit expression was analyzed using qRT-PCR and Western blotting during the first week after seizures. The most pronounced alterations of mRNA and protein levels were observed in the dorsal hippocampus. We found decreased expression of the GluA2 mRNA 7 days after seizures (PSE7), as well as reduced GluN2a protein levels on PSE7. Significant alterations in the expression of different receptor subunits in the mRNA but not protein levels were observed in the entorhinal cortex and amygdala. In contrast, in the medial prefrontal and temporal cortex, we found almost no changes in the expression of the studied genes. The identified changes deepen our understanding of post-seizure disturbances in the developing brain and confirm that although various brain structures are involved in seizures, the hippocampus is the most vulnerable.

Infections in childhood play an essential role in the pathogenesis of cognitive and psycho-emotional disorders. One of the possible mechanisms of these impairments is changes in the functional properties of NMDA and AMPA glutamate receptors in the brain. We suggest that bacterial infections during the early life period, which is critical for excitatory synapse maturation, can affect the subunit composition of NMDA and AMPA receptors. In the present study, we investigated the effect of repetitive lipopolysaccharide (LPS) intraperitoneal (i.p.) administration (25 μg/kg/day on P14, 16, and 18), mimicking an infectious disease, on the expression of subunits of NMDA and AMPA receptors in young rats. We revealed a substantial decrease of GluN2B subunit expression in the hippocampus at P23 using Western blot analysis and real-time polymerase chain reaction assay. Moderate changes were also found in GluN1, GluN2A, and GluA1 mRNA expression. The LPS-treated rats exhibited decreased exploratory and locomotor activity in the open field test and the impairment of spatial learning in the Morris water maze. Behavioral impairments were accompanied by a significant reduction in long-term hippocampal synaptic potentiation. Our data indicate that LPS-treatment in the critical period for excitatory synapse maturation alters ionotropic glutamate receptor gene expression, disturbs synaptic plasticity, and alters behavior.

Temporal epilepsy is a severe neuromental disorder which is difficult to treat and whose pathogenesis is presumptively linked with the development of neuroinflammation, astrogliosis, and neuron death. The least studied of these processes occur in the amygdala, a part of the brain playing an important role in epileptogenesis. This study analyzes the structural and biochemical changes occurring in the basolateral part of the amygdala in a lithium-pilocarpine model of temporal epilepsy. Status epilepticus was induced in Wistar rats aged 7–8 weeks. Two subgroups were identified: one with severe, prolonged convulsions and one with mild short-lived convulsions. This separation was linked with the relationship between the probability of developing spontaneous recurrent convulsions in the chronic phase of the model on the one hand and the severity and duration of convulsions during the period of status epilepticus on the other. Histological studies were performed during the latent and chronic periods of the model (3 and 7 days and 2 months after administration of pilocarpine) using light and electron microscopy methods, as well as immunohistochemical analysis of the distribution of neuronal (Fox3) and glial (GFAP, Iba1) markers in cells. The expression of the genes for the proinflammatory cytokines interleukin-1β (Il1b) and tumor necrosis factor α (Tnfa) was analyzed by reverse transcription and the real-time polymerase chain reaction on day 7 after status epilepticus. During the first week after administration of pilocarpine into the basolateral amygdala, rats with prolonged convulsions showed decreases in the number of neurons and significant increases in the numbers of astrocytes and microglial cells. Rats with short-term convulsions showed no glial reaction and cell death was less extensive. Ultrastructural studies demonstrated accumulations of lysosomes and other neurodegenerative changes in amygdalar neurons of rats with prolonged convulsions. These abnormalities were accompanied by increased expression of the Il1b and Tnfa genes, pointing to the development of neuroinflammatory processes. Changes found in amygdalar cells in rats with severe long-lasting convulsions could be among the key mechanisms of epileptogenesis and associated comorbid behavioral abnormalities.

Epilepsy is a challenging brain disorder that is often difficult to treat with conventional therapies. The gut microbiota has been shown to play an important role in the development of neuropsychiatric disorders, including epilepsy. In this study, the effects of Bifidobacterium longum, a probiotic, on inflammation, neuronal degeneration, and behavior are evaluated in a lithium–pilocarpine model of temporal lobe epilepsy (TLE) induced in young adult rats. B. longum was administered orally at a dose of 109 CFU/rat for 30 days after pilocarpine injection. The results show that B. longum treatment has beneficial effects on the TLE-induced changes in anxiety levels, neuronal death in the amygdala, and body weight recovery. In addition, B. longum increased the expression of anti-inflammatory and neuroprotective genes, such as Il1rn and Pparg. However, the probiotic had little effect on TLE-induced astrogliosis and microgliosis and did not reduce neuronal death in the hippocampus and temporal cortex. The study suggests that B. longum may have a beneficial effect on TLE and may provide valuable insights into the role of gut bacteria in epileptogenesis. In addition, the results show that B. longum may be a promising drug for the comprehensive treatment of epilepsy.

Disrupted glutamate clearance in the synaptic cleft leads to synaptic dysfunction and neurological diseases. Decreased glutamate removal from the synaptic cleft is known to cause excitotoxicity. Data on the physiological effects of increased glutamate clearance are contradictory. This study investigated the consequences of ceftriaxone (CTX), an enhancer of glutamate transporter 1 expression, treatment on long-term synaptic potentiation (LTP) in the hippocampus of young rats. In this study, 5-day administration of CTX (200 mg/kg) significantly weakened LTP in CA3-CA1 synapses. As shown by electrophysiological recordings, LTP attenuation was associated with weakening of N-Methyl-D-aspartate receptor (NMDAR)-dependent signaling in synapses. However, PCR analysis did not show downregulation of NMDAR subunits or changes in the expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits. We assume that extracellular burst stimulation activates fewer synapses in CTX-treated animals because increased glutamate reuptake results in reduced spillover, and neighboring synapses do not participate in neurotransmission. Attenuation of LTP was not accompanied by noticeable behavioral changes in the CTX group, with no behavioral abnormalities observed in the open field test or Morris water maze test. Thus, our experiments show that increased glutamate clearance can impair long-term synaptic plasticity and that this phenomenon can be considered a potential side effect of CTX treatment.

Febrile seizures (FSs) in early life are significant risk factors of neurological disorders and cognitive impairment in later life. However, existing data about the impact of FSs on the developing brain are conflicting. We aimed to investigate morphological and functional changes in the hippocampus of young rats exposed to hyperthermia-induced seizures at postnatal day 10. We found that FSs led to a slight morphological disturbance. The cell numbers decreased by 10% in the CA1 and hilus but did not reduce in the CA3 or dentate gyrus areas. In contrast, functional impairments were robust. Long-term potentiation (LTP) in CA3-CA1 synapses was strongly reduced, which we attribute to the insufficient activity of N-methyl-D-aspartate receptors (NMDARs). Using whole-cell recordings, we found higher desensitization of NMDAR currents in the FS group. Since the desensitization of NMDARs depends on subunit composition, we analyzed NMDAR current decays and gene expression of subunits, which revealed no differences between control and FS rats. We suggest that an increased desensitization is due to insufficient activation of the glycine site of NMDARs, as the application of D-serine, the glycine site agonist, allows the restoration of LTP to a control value. Our results reveal a new molecular mechanism of FS impact on the developing brain.

According to the two-hit hypothesis of psychoneuropathology formation, infectious diseases and other pathological conditions occurring during the critical periods of early ontogenesis disrupt normal brain development and increase its susceptibility to stress experienced in adolescence and adulthood. It is believed that these disorders are associated with changes in the functional activity of the glutamatergic system in the hippocampus. Here, we studied expression of NMDA (GluN1, GluN2a, GluN2b) and AMPA (GluA1, GluA2) glutamate receptor subunits, as well as glutamate transporter EAAT2, in the ventral and dorsal regions of the hippocampus of rats injected with LPS during the third postnatal week and then subjected to predator stress (contact with a python) in adulthood. The tests were performed 25 days after the stress. It was found that stress altered protein expression in the ventral, but not in the dorsal hippocampus. Non-stressed LPS-treated rats displayed lower levels of the GluN2b protein in the ventral hippocampus vs. control animals. Stress significantly increased the content of GluN2b in the LPS-treated rats, but not in the control animals. Stress also affected differently the exploratory behavior of LPS-injected and control rats. Compared to the non-stressed animals, stressed control rats demonstrated a higher locomotor activity during the 1st min of the open field test, while the stressed LPS-injected rats displayed lower locomotor activity than the non-stressed rats. In addition, LPS-treated stressed and non-stressed rats spent more time in the open arms of the elevated plus maze and demonstrated reduced blood levels of corticosterone. To summarize the results of our study, exposure to bacterial LPS in the early postnatal ontogenesis affects the pattern of stress-induced changes in the behavior and hippocampal expression of genes coding for ionotropic glutamate receptor subunits after psychogenic trauma suffered in adulthood.

Reverse transcription followed by quantitative polymerase chain reaction (qRT-PCR) is a powerful and commonly used tool for gene expression analysis. It requires the right choice of stably expressed reference genes for accurate normalization. In this work, we aimed to select the optimal reference genes for qRT-PCR normalization within different brain areas during the first week following pentylenetetrazole-induced seizures in immature (P20&ndash, 22) Wistar rats. We have tested the expression stability of a panel of nine housekeeping genes: Actb, Gapdh, B2m, Rpl13a, Sdha, Ppia, Hprt1, Pgk1, and Ywhaz. Based on geometric averaging of ranks obtained by four common algorithms (geNorm, NormFinder, BestKeeper, Comparative Delta-Ct), we found that the stability of tested reference genes varied significantly between different brain regions. The expression of the tested panel of genes was very stable within the medial prefrontal and temporal cortex, and the dorsal hippocampus. However, within the ventral hippocampus, the entorhinal cortex and amygdala expression levels of most of the tested genes were not steady. The data revealed that in the pentylenetetrazole-induced seizure model in juvenile rats, Pgk1, Ppia, and B2m expression are the most stable within the medial prefrontal cortex, Ppia, Rpl13a, and Sdha within the temporal cortex, Pgk1, Ppia, and Rpl13a within the entorhinal cortex, Gapdh, Ppia, and Pgk1 within the dorsal hippocampus, Rpl13a, Sdha, and Ppia within the ventral hippocampus, and Sdha, Pgk1, and Ppia within the amygdala. Our data indicate the need for a differential selection of reference genes across brain regions, including the dorsal and ventral hippocampus.

The mechanisms of impairment in long-term potentiation after status epilepticus (SE) remain unclear. We investigated the properties of LTP induced by theta-burst stimulation in hippocampal slices of rats 3 h and 1, 3, and 7 days after SE. Seizures were induced in 3-week old rats by a single injection of pentylenetetrazole (PTZ). Only animals with generalized seizures lasting more than 30 min were included in the experiments. The results revealed that LTP was strongly attenuated in the CA1 hippocampal area after PTZ-induced SE as compared with that in control animals. Saturation of synaptic responses following epileptic activity does not explain weakening of LTP because neither the quantal size of the excitatory responses nor the slopes of the input–output curves for field excitatory postsynaptic potentials changed in the post-SE rats. After PTZ-induced SE, NMDA-dependent LTP was suppressed, and LTP transiently switched to the mGluR1-dependent form. This finding does not appear to have been reported previously in the literature. An antagonist of NMDA receptors, d-2-amino-5-phosphonovalerate, did not block LTP induction in 3-h and 1-day post-SE slices. An antagonist of mGluR1, FTIDS, completely prevented LTP in 1-day post-SE slices; whereas it did not affect LTP induction in control and post-SE slices at the other studied times. mGluR1-dependent LTP was postsynaptically expressed and did not require NMDA receptor activation. Recovery of NMDA-dependent LTP occurred 7 day after SE. Transient switching between NMDA-dependent LTP and mGluR1-dependent LTP could play a role in the pathogenesis of acquired epilepsy.

Temporal lobe epilepsy is the most prevalent form of complex partial seizure, and it is frequently triggered by an initial brain-damaging insult. The prevention of epileptogenesis after a primary event could be a key innovative approach to epilepsy treatment. Therefore, it is critical to understand the pathogenic mechanisms of this process in detail. Multiple mechanisms are involved in epileptogenesis, including alterations in the expression of synaptic receptors and transporters. The present study aimed to investigate the mRNA expression of excitatory amino acid transporters 1-3 (EAATs) and the subunits of the NMDA (GluN1, GluN2a, and GluN2b) and AMPA (GluA1 and GluA2) glutamate receptors following status epilepticus in a rat lithium-pilocarpine model. The analysis of the mRNA was performed via qRT-PCR one week after pilocarpine injections (the period of epileptogenesis) into the ventral and dorsal hippocampus and the entorhinal, temporal, and medial prefrontal cortexes - brain areas that are differentially involved in the pathogenesis of TLE. We found that increased EAAT2 mRNA levels in the medial prefrontal cortex and dorsal hippocampus may represent compensatory neuroprotective changes. Alterations in the gene expression levels of AMPA receptor subunits were found in the ventral hippocampus and temporal cortex. The reduced expression of the GluN2a subunit was observed in the temporal and entorhinal cortical areas and the ventral hippocampus, which may result in the predominance of GluN2b-containing NMDA receptors in these areas. The receptors with this altered subunit composition may be involved in pathophysiological mechanisms related to epileptogenesis. These data provide a better understanding of the pathogenesis of epilepsy.

The molecular changes in the glutamatergic system of the rat amygdala were studied during the latent phase of the lithium–pilocarpine model of temporal lobe epilepsy in order to identify the potential involvement of these changes in epileptogenesis. The real-time PCR method was used to evaluate the mRNA expression of the NMDA and AMPA receptor subunits, as well as the excitatory amino acid transporter-2 (EAAT2) in the basolateral nucleus of the amygdala 7 days after the seizures caused by administration of pilocarpine. The results of the experiments were as follows: (1) an increase in the expression ratio of the GluN2a/GluN2b NMDA receptor subunits with an unchanged expression level of the GluN1 subunit; (2) increased expression of the GluA2 subunit of AMPA receptors with the invariance of GluA1, and (3) enhanced expression of the EAAT2. According to literature data, the expression of the same genes decreased in the hippocampus in the same model of epilepsy. Neurodegeneration was reported in both brain regions. The opposite changes in the expression of the glutamatergic system genes in the hippocampus and amygdala during the latent period of the lithium–pilocarpine model suggest the occurrence of factors that can both contribute to and hinder epileptogenesis.

We studied modifications in the glutamatergic system of the brain as a factor in the development of post-traumatic stress disorder. An analysis of mRNA production of NMDA (GluN1, GluN2a, and GluN2b) and AMPA (GluA1 and GluA2) glutamate receptors, as well as the EAAT2 glutamate transporter was performed in the brain of rats subjected to stress associated with contact with a predator (a black-tailed python). Studies were performed in 6 or 24 h as well as in 3, 9, and 25 days after stress. The most-pronounced alterations of expression of all studied genes were revealed 25 days after stress. The level of EAAT2 mRNA increased in the ventral hippocampus. The expression of the genes that encode GluA1 and GluA2 subunits of AMPA receptors decreased in the dorsal and increased in the ventral hippocampus. The changes in the expression of the gene that encodes the GluN2b subunit of the NMDA receptor were also region specific. In the ventral hippocampus and medial prefrontal cortex we observed an increase in the expression of GluN2b mRNA, while it decreased in the dorsal hippocampus. The increased expression of the gene that encodes the GluN2a subunit was found in the amygdala. These alterations may be a mechanism of the development of delayed post-stress neurological–psychiatric impairments.

Cognitive deficits and memory loss are frequent in patients with temporal lobe epilepsy. Persistent changes in synaptic efficacy are considered as a cellular substrate underlying memory processes. Electrophysiological studies have shown that the properties of short-term and long-term synaptic plasticity in the cortex and hippocampus may undergo substantial changes after seizures. However, the neural mechanisms responsible for these changes are not clear. In this study, we investigated the properties of short-term and long-term synaptic plasticity in rat hippocampal slices 24 h after pentylenetetrazole (PTZ)-induced status epilepticus. We found that the induction of long-term potentiation (LTP) in CA1 pyramidal cells is reduced compared to the control, while short-term facilitation is increased. The experimental results do not support the hypothesis that status epilepticus leads to background potentiation of hippocampal synapses and further LTP induction becomes weaker due to occlusion, as the dependence of synaptic responses on the strength of input stimulation was not different in the control and experimental animals. The decrease in LTP can be caused by impairment of molecular mechanisms of neuronal plasticity, including those associated with NMDA receptors and/or changes in their subunit composition. Real-time PCR demonstrated significant increases in the expression of GluN1 and GluN2A subunits 3 h after PTZ-induced status epilepticus. The overexpression of obligate GluN1 subunit suggests an increase in the total number of NMDA receptors in the hippocampus. A 3-fold increase in the expression of the GluN2B subunit observed 24 h after PTZ-induced status epilepticus might be indicative of an increase in the proportion of GluN2B-containing NMDA receptors. Increased expression of the GluN2B subunit may be a cause for reducing the magnitude of LTP at hippocampal synapses after status epilepticus.

Infectious diseases in early postnatal ontogenesis often result in cognitive impairments, particularly learning and memory. The essential foundation of learning and memory is long-term synaptic plasticity, which depends on N-methyl-D-aspartate (NMDA) receptors. In the present study, bacterial infection was modeled by treating rat pups with bacterial lipopolysaccharide (LPS, 25 &micro, g/kg) three times, during either the first or the third week of life. These time points are critical for the maturation of NMDA receptors. We assessed the effects of LPS treatments on the properties of long-term potentiation (LTP) in the CA1 hippocampus of young (21&ndash, 23 days) and adolescent (51&ndash, 55 days) rats. LTP magnitude was found to be significantly reduced in both groups of young rats, which also exhibited investigative and motor behavior disturbances in the open field test. No changes were observed in the main characteristics of synaptic transmission, although the LTP induction mechanism was disturbed. In rats treated with LPS during the third week, the NMDA-dependent form of LTP was completely suppressed, and LTP switched to the Type 1 metabotropic glutamate receptor (mGluR1)-dependent form. These impairments of synaptic plasticity and behavior were temporary. In adolescent rats, no difference was observed in LTP properties between the control and experimental groups. Lastly, the investigative and motor behavior parameters in both groups of adult rats were similar.

Epilepsy is a common neurological disorder. Despite the availability of a wide range of antiepileptic drugs, these are unsuccessful in preventing seizures in 20&ndash, 30% of patients. Therefore, new pharmacological strategies are urgently required to control seizures. Modulation of glutamate uptake may have potential in the treatment of pharmacoresistant forms of epilepsy. Previous research showed that the antibiotic ceftriaxone (CTX) increased the expression and functional activity of excitatory amino acid transporter 2 (EAAT2) and exerted considerable anticonvulsant effects. However, other studies did not confirm a significant anticonvulsant effect of CTX administration. We investigated the impacts of CTX treatment on EAAT expression and glutamatergic neurotransmission, as well its anticonvulsant action, in young male Wistar rats. As shown by a quantitative real-time polymerase chain reaction (qPCR) assay and a Western blot analysis, the mRNA but not the protein level of EAAT2 increased in the hippocampus following CTX treatment. Repetitive CTX administration had only a mild anticonvulsant effect on pentylenetetrazol (PTZ)-induced convulsions in a maximal electroshock threshold test (MEST). CTX treatment did not affect the glutamatergic neurotransmission, including synaptic efficacy, short-term facilitation, or the summation of excitatory postsynaptic potentials (EPSPs) in the hippocampus and temporal cortex. However, it decreased the field EPSP (fEPSP) amplitudes evoked by intense electrical stimulation. In conclusion, in young rats, CTX treatment did not induce overexpression of EAAT2, therefore exerting only a weak antiseizure effect. Our data provide new insight into the effects of modulation of EAAT2 expression on brain functioning.

The aim of this study was to evaluate in detail behavioral patterns and comorbid disturbances in rats using the lithium-pilocarpine model. A comprehensive set of behavioral tests was used to investigate behavioral patterns, including the open field test, Morris water maze, Y-maze, fear conditioning, the elevated plus maze, the forced swimming test, and the resident-intruder paradigm. Motor and explorative activity, learning and memory, anxiety and depressive-like behavior, aggression, and communication were evaluated 8-15 d after pilocarpine-induced status epilepticus (SE) (latent phase of the model) and 41-53 d (chronic phase) after pilocarpine-induced SE. Increased motor activity and impaired memory function were the most noticeable behavioral modifications in the epileptic rats. Both the movement speed and distance traveled increased in the open field test in both the latent and chronic phases. Significant impairments were detected in short-and long-term spatial memory in the Morris water maze during the latent phase. Besides the alterations in spatial memory, behaviors indicative of short- and long-term fear-associated memory disturbances were observed in the fear conditioning test during the chronic phase of the model. In the resident-intruder paradigm, epileptic rats exhibited disturbed communicative behavior, with impaired social behaviors. In contrast, emotional disturbances were less prominent, with the rats exhibiting decreased anxiety. There were no changes in depressive-like behavior. The data suggest that the lithium-pilocarpine model of TLE in rodents is more useful for studies of comorbid disturbances in memory, hyperactivity, and social behavior than for research on psychoemotional impairments, such as anxiety and depression.

The mechanisms of impairment in long-term potentiation after status epilepticus (SE) remain unclear. We investigated the properties of LTP induced by theta-burst stimulation in hippocampal slices of rats 3 h and 1, 3, and 7 days after SE. Seizures were induced in 3-week old rats by a single injection of pentylenetetrazole (PTZ). Only animals with generalized seizures lasting more than 30 min were included in the experiments. The results revealed that LTP was strongly attenuated in the CA1 hippocampal area after PTZ-induced SE as compared with that in control animals. Saturation of synaptic responses following epileptic activity does not explain weakening of LTP because neither the quantal size of the excitatory responses nor the slopes of the input-output curves for field excitatory postsynaptic potentials changed in the post-SE rats. After PTZ-induced SE, NMDA-dependent LTP was suppressed, and LTP transiently switched to the mGluR

The capability of memantine, a noncompetitive antagonist of the NMDA receptors, to prevent impairments of cognitive functions in rats was investigated in the lithium-pilocarpine model of epilepsy. After status epilepticus, rats exhibited impaired exploratory behavior and spatial memory, and a decline of extinction of orienting behavior. Memantine administration prevented these disturbances. Thus, the blockade of the NMDA receptors immediately after status epilepticus allowed prevention of the development of the possible cognitive impairments.

Temporal lobe epilepsy (TLE) is the most common type of epilepsy in humans. The lithium-pilocarpine model in rodents reproduces some of the main features of human TLE. Three-week-old Wistar rats were used in this study. The changes in AMPA receptor subunit composition were investigated in several brain areas, including the medial prefrontal cortex (mPFC), the temporal cortex (TC), and the dorsal (DH) and ventral hippocampus (VH) during the first week following pilocarpine-induced status epilepticus (PILO-induced SE). In the hippocampus, GluA1 and GluA2 mRNA expression slightly decreased after PILO-induced SE and returned to the initial level on the seventh day. We did not detect any significant changes in mRNA expression of the GluA1 and GluA2 subunits in the TC, whereas in the mPFC we observed a significant increase of GluA1 mRNA expression on the third day and a decrease in GluA2 mRNA expression during the entire first week. Accordingly, the GluA1/GluA2 expression ratio increased in the mPFC, and the functional properties of the pyramidal cell excitatory synapses were disturbed. Using whole-cell voltage-clamp recordings, we found that on the third day following PILO-induced SE, isolated mPFC pyramidal neurons showed an inwardly rectifying current-voltage relation of kainate-evoked currents, suggesting the presence of GluA2-lacking calcium-permeable AMPARs (CP-AMPARs). IEM-1460, a selective antagonist of CP-AMPARs, significantly reduced the amplitude of evoked EPSC in pyramidal neurons from mPFC slices on the first and third days, but not on the seventh day. The antagonist had no effects on EPSC amplitude in slices from control animals. Thus, our data demonstrate that PILO-induced SE affects subunit composition of AMPARs in different brain areas, including the mPFC. SE induces transient (up to few days) incorporation of CP-AMPARs in the excitatory synapses of mPFC pyramidal neurons, which may disrupt normal circuitry functions.

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