In this study, we investigated how midazolam and d-cycloserine regulate the tonic activity and/or phasic reactivity of brain neurotransmitter systems to fear-evoking stimuli in rats with varying intensities of a fear response. We used a new animal model composed of high (HR) and low (LR) anxiety rats, selected according to their behaviour in the contextual fear test (i.e.
View Article and Find Full Text PDFThis work attempted to answer the question whether the central processes engaged in the memory formation and the epilepsy development are governed by the overlapping mechanisms. The effects of the protein synthesis inhibitor cycloheximide (CHX) were examined on the expression and reconsolidation of pentylenetetrazole (PTZ) - induced kindled seizures and for comparative purposes, on the reconsolidation of conditioned fear response (conditioned freezing). It was found that post-test intracerebroventricular administration of CHX (125microg/5microl) significantly attenuated the expression of a conditioned fear response examined 24h later.
View Article and Find Full Text PDFThis work attempted to "biochemically" map the brain structures that are recruited at the different stages of pentylenetetrazole (PTZ) kindling (in a model of temporal lobe epilepsy induced by a repeated, systemic administration of PTZ, at a subconvulsive dose of 35 mg/kg). We observed substantial changes in the levels of noradrenaline (NA), 5-hydroxytryptamine (5-HT), dopamine (DA), and their metabolites in the brain structures known to be recruited in the course of kindling, i.e.
View Article and Find Full Text PDFThe results showed that the development of seizures (pentylenetetrazole, PTZ-induced kindling; PTZ was administered to rats at a subconvulsive dose of 35mg/kg three times a week, i.p.) was accompanied by a progressive recruitment of limbic structures and a characteristic pattern of changes in the brain tissue concentration of examined amino acids (ex vivo measurements, 1.
View Article and Find Full Text PDFc-Fos protein immunocytochemistry was used to map the brain structures recruited during the evolution of seizures that follows repeated administration of a subconvulsive dose (35mg/kg, ip) of pentylenetetrazol in rats. c-Fos appeared earliest in nucleus accumbens shell, piriform cortex, prefrontal cortex, and striatum (stages 1 and 2 of kindling in comparison to control, saline-treated animals). At the third stage of kindling, central amygdala nuclei, entorhinal cortex, and lateral septal nuclei had enhanced concentrations of c-Fos.
View Article and Find Full Text PDFWe designed an animal model to examine the mechanisms of differences in individual responses to aversive stimuli. We used the rat freezing response in the context fear test as a discriminating variable: low responders (LR) were defined as rats with a duration of freezing response one standard error or more below the mean value, and high responders (HR) were defined as rats with a duration of freezing response one standard error or more above the mean value. We sought to determine the colocalisation of c-Fos and glucocorticoid receptors-immunoreactivity (GR-ir) in HR and LR rats subjected to conditioned fear training, two extinction sessions and re-learning of a conditioned fear.
View Article and Find Full Text PDFBackground And Purpose: Previous studies suggested that biochemical markers of brain damage could act as prognostic factors in ischaemic stroke. The aim of the present study was to assess predictive value of the selected biomarkers S100B protein, neuron-specific enolase (NSE), C-reactive protein (CRP) and D-dimers, as well as GABA and excitatory amino-acids (EAA) measured in blood for 3-month functional outcome in ischaemic stroke patients.
Material And Methods: We investigated 54 patients with ischaemic stroke (mean age: 73.
Considering the contribution of hippocampal formation and glutamate-mediated signalling to epileptogenesis, we investigated the effects of group III metabotropic glutamate receptor (mGluR)-selective ligands on the kindling of seizures. We also examined the concentration of the amino acid glutamate, GABA, alanine and taurine in the hippocampus of rats using a microdialysis technique. Pentylenetetrazol (PTZ), a non-competitive antagonist of the GABA(A) receptor, was administered intraperitoneally at 35 mg/kg body weight to induce seizures.
View Article and Find Full Text PDFThe effects of intracerebroventricular injections of CRF and a non-selective CRF receptor antagonist, alpha-helical CRF((9-41)), on the release of glutamate, aspartate, and GABA in the central nucleus of the amygdala (CeA), were examined in the course of testing rat anxiety-like behaviour in the conditioned fear test (a freezing response), using the microdialysis technique. It was found that CRF (1 microg/rat), given to animals exposed to the stress of novelty only, insignificantly increased the glutamate concentration in the CeA, up to 200% of the control level. In the fear-conditioned animals, the influence of CRF on the local concentration of aspartate, glutamate, and Glu/GABA ratio was much more pronounced (up to a 400% increase above the baseline level of aspartate concentration), preceded an increased expression of anxiety-like responses, and appeared as early as 15 min after the drug administration.
View Article and Find Full Text PDFWe sought to determine the colocalisation of c-Fos (a marker of neuronal activation) and glucocorticoid receptors (GRs) as well as of 5-HT(1A) and glucocorticoid receptor immunoreactivity-expressing cells (ir) in the dorsomedial prefrontal cortex (M2), dentate gyrus of the hippocampus (DG), and basolateral nucleus of the amygdala (BLA) in low and high anxiety rats (i.e., rats with duration of a freezing response in the conditioned fear test one standard error or more below or above the mean value: low responders (LR) and high responders (HR), respectively).
View Article and Find Full Text PDFThe effect of an anxiolytic drug, midazolam, on the expression of c-Fos protein (the product of the immediate early gene, c-fos) in the rat brain was studied in animals that were exposed to the stress of neophobia using the open field test. Midazolam (0.5 mg/kg, ip) selectively and significantly attenuated the neophobia-induced increase in the number of Fos-like immunoreactive neurons in the dorsomedial part of the prefrontal cortex, but not in the primary motor cortex, the piriform cortex or the amygdalar nuclei.
View Article and Find Full Text PDFThe time response of changes in the brain concentration of kynurenic acid (KYNA) was examined in rats subjected to the pentylenetetrazol (PTZ)-induced kindling of seizures (n=32). The development of seizures was accompanied by a progressive decrease in KYNA concentration in the caudate putamen, entorhinal cortex, piriform cortex, amygdala and hippocampus. A single injection of PTZ (35 mg/kg i.
View Article and Find Full Text PDFIn the present study we have examined the influence of intracerebroventricullary administered CRF, and a non-selective CRF receptor antagonist, alpha-helical CRF((9-41)), on rat conditioned fear response, serum corticosterone, c-Fos and CRF expression, and concentration of amino acids (in vitro), in several brain structures. Pretreatment of rats with CRF in a dose of 1 microg/rat, enhanced rat-freezing response, and further increased conditioned fear-elevated concentration of serum corticosterone. Moreover, exogenous CRF increased aversive context-induced expression of c-Fos in the parvocellular neurons of the paraventricular hypothalamic nucleus (pPVN), CA1 area of the hippocampus, and M1 area of the frontal cortex.
View Article and Find Full Text PDFIt is not well recognized how disturbances in the local metabolism of some amino acids, especially glutamate and GABA, may lead to seizures. In the presented study, we have examined changes in the hippocampal steady state concentrations of amino acids involved in pentylenetetrazole-kindled and freely moving rats. It was found that in the kindled animals, the concentration of alanine, arginine, glutamate, aspartate and taurine was increased in the interictal period of seizures compared to the control group, whereas kindling reduced the extracellular levels of GABA.
View Article and Find Full Text PDFIn this study we have explored differences in animal reactivity to conditioned aversive stimuli using the conditioned fear test (a contextual fear-freezing response), in rats subjected to the selective lesion of the prefrontal cortex serotonergic innervation, and differing in their response to the acute painful stimulation, a footshock (HS--high sensitivity rats, and LS--low sensitivity rats, selected arbitrarily according to their behavior in the 'flinch-jump' pre-test). Local administration of serotonergic neurotoxin (5,7-dihydroxytryptamine) to the dorsomedial part of the prefrontal cortex caused a very strong, structure and neurotransmitter selective depletion of serotonin concentration. In HS rats, the serotonergic lesion significantly disinhibited rat behavior controlled by fear, enhanced c-Fos expression in the dorsomedial prefrontal area, and increased the concentration of GABA in the basolateral amygdala, measured in vivo after the testing session of the conditioned fear test.
View Article and Find Full Text PDFThe effects of anxiolytic doses of buspirone and midazolam (established in the conditioned fear test) on extracellular concentrations of glutamate, GABA, serotonin and dopamine metabolites in the hippocampus were examined in vivo, in freely moving rats. Buspirone at a dose of 1.5 mg/kg ip disinhibited rat behavior in the conditioned fear test (a freezing response) much stronger than 1.
View Article and Find Full Text PDFThe effects of acute rise in corticosterone concentration upon the levels of hippocampal glutamate (Glu) are well described. Much less is known about the effect of chronic elevation of glucocorticoids on hippocampal glutamate. This is an important question, given the role of glutamate in the neurodegenerative and cognitive effects of chronic stressors.
View Article and Find Full Text PDFThe aim of the study was to examine the neurochemical background of differences in the individual responses to conditioned aversive stimuli, using the strength of a rat conditioned freezing response (the contextual fear test), as a discriminating variable. It was shown that low responders (LR), i.e.
View Article and Find Full Text PDFThe effects of acute pretreatment of rats with corticosterone (5 and 20 mg/kg, s.c.) on emotional behavior, expression of c-Fos protein in brain structures, and serum concentration of corticosterone were studied to model the short-term glucocorticoid-dependent changes in brain functions.
View Article and Find Full Text PDFThe aim of the study was to investigate the role of the periaqueductal gray (PAG) in anxiolytic-like actions of fluoxetine in animals treated with an anxiogenic drug, pentylenetetrazol (PTZ), and subjected to fear conditioning procedure. The data showed that PTZ given at the dose of 30 mg/kg 15 min before a retention trial significantly decreased freezing reaction (p<0.01), and potently enhanced rat locomotor activity (p<0.
View Article and Find Full Text PDFThe aim of this paper was to examine changes in rat emotional behavior, and to find the brain structures, which are involved in the mediation of behavioral effects, related to the repeated administration of glucocorticoids. The effects of acute and chronic pretreatment of rats with two doses of corticosterone (5 and 20 mg/kg) were analyzed in two models of fear responses: neophobia-like behavior in the open field test, and freezing reaction in the conditioned fear test. Behavioral effects of repeated glucocorticoid administration were compared to changes in blood total corticosterone concentration, and expression of immediate early gene (c-Fos) in brain structures.
View Article and Find Full Text PDFThe aim of the study was to further explore the anatomical and neurochemical background of differences in response to the conditioned aversive stimuli. The different patterns of behavioral coping strategies (a conditioned freezing response and ultrasonic vocalization) were analyzed in animals differing in their response to the acute painful stimulation, a foot-shock (HS: high sensitivity rats, LS: low sensitivity rats, and MS: medium sensitivity rats, according to their behavior in the flinch-jump pre-test), and correlated with plasma corticosterone levels, expression of c-Fos protein, and distribution of 5-HT innervation, in different brain structures. It was found that HS rats showed significantly more freezing behavior, whereas LS animals vocalized much more intensively.
View Article and Find Full Text PDFThis is the first study designed to compare the pattern of stimulation of c-Fos in selected brain structures after an acute administration of morphine and methadone. Methadone and morphine induced activation of c-Fos protein in the terminal forebrain projecting areas of the brain dopaminergic system, i.e.
View Article and Find Full Text PDFThe effects of kindled seizures elicited by repeated pentetetrazole (PTZ) injections, on learning and memory in the Morris water maze test and on concentration of brain amino acids, were examined in rats. It was found that kindled seizures (a model of temporal lobe epilepsy) produced a profound decrease in learning and memory accompanied by a selective and long-lasting decrease in hippocampal and striatal concentration of glutamate, glycine and alanine in the striatum (ex vivo measurement). The concentrations of histamine, serine and gamma-aminobutyric acid (GABA) were not selectively affected by kindling.
View Article and Find Full Text PDFStudy Aim: To asses the results of phototherapy on platelet serotonin transport in the group of patients with seasonal affective disorder (SAD), DSM-IV criteria, with complete clinical remission during the summer period.
Methods: It was a 3 year prospective study. 33 patients were qualified, 20 participated in at least two assessments (before and after light treatment) and were included in the final analysis.