Publications (34)90.18 Total impact
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Article: The kynurenine pathway: a missing piece in the puzzle of valproate action?
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ABSTRACT: The present study was designed to determine the role of the kynurenine pathway (KP) in the mechanism of action of valproate (VPA). Therefore, we investigated changes in the concentrations of tryptophan, kynurenic acid, and kynurenine in the brain and plasma following VPA administration (50, 250 and 500 mg/kg i.p.). The most important findings of our study were that VPA administration produced a progressive and strong increase in the central concentrations of kynurenic acid, kynurenine and tryptophan. Simultaneously, the TRP level in plasma declined, while the peripheral increase of kynurenic acid in plasma was weaker and occurred earlier than in the hippocampus. Bearing in mind that the observed effect may be a result of a strong VPA-induced displacement of tryptophan from its binding sites to plasma albumin, we checked the effect of ibuprofen administration (a prototypic drug used to study drug binding to serum albumin) on the KP. We found that ibuprofen evoked a similar pattern of changes in the KP activity as VPA. These new findings indicate the existence of a mechanism that could stimulate the production of kynurenic acid in the brain after VPA administration, and may partially contribute to the mechanisms of VPA action. The results of our experiment indicate that an increase in the brain's KYNA level may be achieved by TRP displacement from its binding site on the plasma albumin with the administration of different drugs, including VPA, ibuprofen, or short-chain fatty acids, with important clinical consequences.Neuroscience 01/2013; · 3.38 Impact Factor -
Article: Kynurenic acid: a new effector of valproate action?
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ABSTRACT: We investigated the changes in hippocampal kynurenic acid (KYNA) concentrations and the amino acids involved in neuronal activity regulation following valproate (VPA) administration (400 mg/kg ip) in pentylenetetrazole-kindled rats (in vivo). We found a remarkably long-lasting increase in KYNA levels following VPA administration, and this effect correlated with a rise in GABA levels. No changes in the concentration of other analyzed amino acids were present. It is likely that the antiepileptic and neuroprotective properties of VPA may also be a consequence of an increase in the hippocampal KYNA concentration.Pharmacological reports: PR 11/2011; 63(6):1569-73. · 2.44 Impact Factor -
Article: Effects of D-cycloserine and midazolam on the expression of the GABA-A alpha-2 receptor subunits in brain structures of fear conditioned rats.
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ABSTRACT: The role of the GABA-A alpha-2 receptor subunit in the basolateral amygdala (BLA), dentate gyrus of the hippocampus (DG) and prefrontal cortex (M2 area) during a fear session (performed one week after the conditioned fear test), was studied. We employed a model of high (HR) and low anxiety (LR) rats divided according to their conditioned freezing response. Pretreatment of rats with d-cycloserine immediately before the fear session attenuated fear response in HR and LR rats and increased the density of alpha-2 subunits in the BLA, M2 area and DG of HR animals. The less potent behavioural influence of midazolam (in HR group only) was linked to the increased expression of alpha-2 subunit in M2 area and DG. These results support a role of the GABA-A receptor alpha-2 subunit in processing of emotional cortico-hippocampal input to the BLA.Behavioural brain research 08/2011; 225(2):655-9. · 3.22 Impact Factor -
Article: Diverse behavioral, monoaminergic and Fos protein responses to opioids in Warsaw high-alcohol preferring and Warsaw low-alcohol preferring rats.
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ABSTRACT: Predisposition to addictions is presumably related to a dysfunction of the brain reward system, which can be 'compensated' by the intake of different psychoactive drugs. Hence, animals showing propensity for developing dependence to a specific drug class may also be useful for modeling other addictions. We compared the effects of repeated (14 daily doses) morphine (10 mg/kg) or methadone (2 mg/kg) treatment followed by a 2-week withdrawal and a morphine challenge (5 mg/kg) on locomotor activity, brain Fos expression and selected brain regional levels of dopamine, serotonin and their metabolites in the 38th generations of selectively bred Warsaw low-alcohol-preferring (WLP) and Warsaw high-alcohol-preferring (WHP) rat lines. The rats were given the opioids during the active (i.e. dark) phase of their daily cycle. Drug-naïve WHP rats compared to their WLP counterparts showed higher locomotor activity in an open field test and higher propensity for lasting behavioral sensitization to morphine. Morphine did not significantly enhance, but suppressed Fos expression in certain brain regions of drug-naïve WLP and WHP rats. Fos expression revealed considerable differences in the responses of WLP and WHP rats to morphine challenge, particularly after methadone pretreatment. These differences were associated with differences in monoamine metabolite levels that were suggestive of elevated basal ganglia and lowered frontal cortical dopamine function, and of lowered somatosensory cortex serotonin function, in the morphine-challenged WHP rats (irrespective of the pretreatment type). Hence, the WLP/WHP line pair may be useful for the search of factors that underlie the propensity for developing opiate dependence.Progress in Neuro-Psychopharmacology and Biological Psychiatry 01/2011; 35(2):588-97. · 3.25 Impact Factor -
Article: Differences in the density of GABA-A receptor alpha-2 subunits and gephyrin in brain structures of rats selected for low and high anxiety in basal and fear-stimulated conditions, in a model of contextual fear conditioning.
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ABSTRACT: In this paper we used a model of individual differences in fear responses in rats selected according to their low and high freezing response in the contextual fear test and termed these animals "low- and high anxiety" rats, respectively. We studied differences in the density of GABA-A receptor alpha-2 subunits and gephyrin in the brain structures of low (LR) and high (HR) anxiety rats subjected to extinction trials and re-learning of a conditioned fear response. We found different patterns of spontaneous (western blotting) and fear-stimulated expression of alpha-2 subunits and gephyrin (western blotting and immunocytochemistry) in brain structures of HR and LR animals. Increased basal concentrations of alpha-2 subunits in the amygdala were observed in HR rats (compared to unconditioned control group). The density of alpha-2 subunits in the amygdala negatively correlated with freezing response duration in the aversive context on re-learning in the same group of animals. This finding supports data on the role of GABA-A receptor alpha-2 subunits in the amygdala in modulation of anxiety-like behaviour. Western blotting revealed that exposure of HR animals to fear-conditioned context upon re-test of the conditioned fear test elevated the concentration of alpha-2 subunits in the amygdala and prefrontal cortex. In addition, immunocytochemistry showed that conditioned fear increased the number of cells co-expressing alpha-2 subunits and gephyrin in the basolateral amygdala and dentate gyrus of the hippocampus in the HR group. Together, these findings suggest that animals that are more vulnerable to stress differ in the intracellular mechanisms that control GABA-A receptor trafficking in limbic structures (hippocampus and amygdala), which are involved in the control of emotional behaviour. These data indicate a possible mechanism for the variable effects of benzodiazepines among patients with anxiety disorders. The obtained data may also help to better explain the neurobiological mechanisms that operate in clinical situations where anxious patients subjected to exposure therapy are exposed to an aversive, contextual and conditioning stimulus.Neurobiology of Learning and Memory 11/2010; 94(4):499-508. · 3.42 Impact Factor -
Article: The effects of midazolam and D-cycloserine on the release of glutamate and GABA in the basolateral amygdala of low and high anxiety rats during extinction trial of a conditioned fear test.
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ABSTRACT: 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., the duration of a freezing response was used as a discriminating variable). In these rats, we examined the effects of both drugs on the release of glutamate and GABA in the basolateral amygdala (BLA) during the first extinction trial of a conditioned fear test. The results showed that administration of d-cycloserine (15 mg/kg, i.p.) significantly enhanced the inhibition of an aversive context-induced freezing response observed during the extinction session in HR and LR rats. In contrast, midazolam (0.75 mg/kg, i.p.) accelerated the attenuation of fear responses only in HR rats. The less anxious behaviour of LR animals given saline was accompanied by elevated basal levels of glutamate in the BLA, in comparison with HR rats, and a stronger elevation of GABA in response to contextual fear. In HR animals, the pretreatment of rats with d-cycloserine and midazolam significantly increased the local concentration of GABA and inhibited the expression of contextual fear. These findings suggest that animals more vulnerable to stress have innate deficits in brain systems that control the activity of the BLA mediating the central effect of stress. These results contribute to our understanding of observed individual differences in the effects of anxiolytic drugs among patients with anxiety disorders.Neurobiology of Learning and Memory 11/2010; 94(4):468-80. · 3.42 Impact Factor -
Article: The differential effects of protein synthesis inhibition on the expression and reconsolidation of pentylenetetrazole kindled seizures.
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ABSTRACT: This 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. Thus, inhibition of de novo brain protein synthesis interfered with the reconsolidation of a conditioned response. CHX given at the same dose repeatedly to fully kindled rats immediately after three consecutive sessions of PTZ-induced seizures (35mg/kg ip) did not modify the strength of convulsions. On the other hand, CHX significantly attenuated the strength of convulsions when the drug was administered 1h before the PTZ injection, which occurred every second day for three consecutive sessions. However, when CHX was omitted in a consecutive session, PTZ induced a fully developed expression of tonic-clonic convulsions, thereby indicating that CHX-induced changes in seizure intensity were transitory. Western Blot analysis confirmed that CHX potently inhibited PTZ-induced protein synthesis (c-Fos) in the rat brain, examined 60min after CHX and PTZ administration. The present findings suggest that the mechanisms underlying kindling are resistant to modification, even under the influence of protein synthesis inhibitors, and that there are important differences between the processes of learning and kindling seizures.Epilepsy & Behavior 07/2010; 18(3):193-200. · 2.34 Impact Factor -
Article: Time course of changes in the concentrations of amino acids in the brain structures of pentylenetetrazole-kindled rats.
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ABSTRACT: The 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, 1.5h after the last dose of PTZ). The earliest and homogenous increase in the excitatory (glutamate and alanine) and inhibitory (GABA and taurine) amino acids was observed in the entorhinal cortex (at stages 1 and 2 according to Racine's scale), and this effect was maintained at the fifth stage of kindling (except for glutamate). At the fifth stage of kindling, glutamate was elevated in the amygdala, nucleus accumbens and piriform cortex, whereas alanine content was increased in the hippocampus, amygdala, striatum, nucleus accumbens and piriform cortex. In the case of GABA, a significant increase in the local concentration of this amino acid was found in rats with stage 1 and 2 seizures in the prefrontal and entorhinal cortices and a decrease was present in amygdala. Kindling raised the local level of taurine in the entorhinal cortex (stage 1 and 2 seizures), amygdala, nucleus accumbens and piriform cortex (stage 5 seizures). These data confirm the conclusion that separate seizure circuitries in the forebrain structures mutually interact to facilitate and/or inhibit one another. Overall, these data suggest that there is a shift in the balance between neurotransmitters toward increased production of excitatory amino acids.Brain research 06/2010; 1342:150-9. · 2.46 Impact Factor -
Article: Time course of changes in the concentrations of monoamines in the brain structures of pentylenetetrazole-kindled rats.
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ABSTRACT: This 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., the piriform, entorhinal and prefrontal cortices, and the hippocampus (in vitro). Kindling of seizures induced time-, seizure-, and structure-dependent increases in the local levels of NA, 5-HT, 5-hydroxyindolacetic acid, DA, homovanillic acid, and 3,4-dihydroxyphenylacetic acid. Surprisingly, limited changes in monoamines (NA and 5-HT) were found in the amygdala. The most potent and widespread effects concerned the serotonergic system, indicating a possible protective role of its enhanced activity in the control of the kindling of seizures. These new data indicate a pattern of changes in the basal activity of local monoaminergic innervation of brain limbic structures, accompanying the induction and propagation of seizures.Acta Neurovegetativa 06/2010; 117(6):707-18. · 2.73 Impact Factor -
Article: The influence of the long-term administration of Curcuma longa extract on learning and spatial memory as well as the concentration of brain neurotransmitters and level of plasma corticosterone in aged rats.
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ABSTRACT: The effects of chronic pre-treatment with a standardised extract of Curcuma longa on learning and spatial memory in aged 24-month old male Wistar rats were estimated in a Morris water maze paradigm. Animals received the extract orally for two months in prepared rodent chow to obtain the doses 10 and 50mg/kg/day. At the end of behavioural trials the concentration of neurotransmitters, their metabolites and amino acids in selected brain regions were estimated. There was a significant decrease in escape latency over four days of training in both treated groups in comparison to the control group. In a probe trial on the 5th day the C10 group crossed the target area more often and spent more time in the SE quadrant than control group. Significant differences in brain monoamines and amino acid levels between groups were noticed. The increase in the 5-HT (5-hydroxytryptamine) level in the prefrontal cortex correlated positively with the number of crossings over the target area during the first probe trial in both pre-treated groups. The plasma corticosterone level was lower in both pre-treated groups than in the control group. This suggests enhanced learning ability and spatial memory after C.longa extract treatment with the modulation of central serotoninergic system activity, and may be linked with an increased tolerance to stress conditions. A decrease in hippocampal glutamate in animals given plant extract compared to control rats was observed. It is possible that extract may influence a reduction in glutamate-induced excitotoxicity and consequently the neurodegeneration processes in the hippocampus.Pharmacology Biochemistry and Behavior 02/2010; 95(3):351-8. · 2.53 Impact Factor -
Article: Mapping of c-Fos expression in the rat brain during the evolution of pentylenetetrazol-kindled seizures.
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ABSTRACT: c-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. At the fourth stage of kindling, c-Fos expression was increased in basolateral amygdala and CA1 area of the hippocampus. Finally, c-Fos labeling was enhanced in the dentate gyrus of the hippocampus only when tonic-clonic convulsions were fully developed. The most potent changes in c-Fos were observed in dentate gyrus, piriform cortex, CA1, lateral septal nuclei, basolateral amygdala, central amygdala nuclei, and prefrontal cortex. Piriform cortex, entorhinal cortex, prefrontal cortex, lateral septal nuclei, and CA3 area of the hippocampus appeared to be the brain structures selectively involved in the process of chemically induced kindling of seizures.Epilepsy & Behavior 09/2009; 16(2):216-24. · 2.34 Impact Factor -
Article: The expression of c-Fos and colocalisation of c-Fos and glucocorticoid receptors in brain structures of low and high anxiety rats subjected to extinction trials and re-learning of a conditioned fear response.
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ABSTRACT: We 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. We found that HR animals showed a marked decrease in conditioned fear in the course of two extinction sessions (16 days) in comparison with the control and LR groups. The LR group exhibited higher activity in the cortical M2 and prelimbic areas (c-Fos) and had an increased number of cells co-expressing c-Fos and GR-ir in the M2 and medial orbital cortex after re-learning a contextual fear. HR rats showed increased expression of c-Fos, GR-ir and c-Fos/GR-ir colocalised neurons in the basolateral amygdala and enhanced c-Fos and GR-ir in the dentate gyrus (DG) in comparison with LR animals. Our data indicate that recovery of a context-related behaviour upon re-learning of contextual fear is accompanied in HR animals by a selective increase in c-Fos expression and GRs-ir in the DG area of the hippocampus.Neurobiology of Learning and Memory 08/2009; 92(4):535-43. · 3.42 Impact Factor -
Article: Colocalisation of c-Fos and glucocorticoid receptor as well as of 5-HT(1A) and glucocorticoid receptor immunoreactivity-expressing cells in the brain structures of low and high anxiety rats.
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ABSTRACT: We 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). It was found that 1.5 h after a testing session of the conditioned fear test, the LR animals had a higher activity of the cortical M2 area and DG (c-Fos), a higher expression of GRs-ir, as well as an increased number of cells co-expressing c-Fos and GRs-ir in the same brain areas. In the case of HR rats, they had similar expression of c-Fos in the BLA, but a significantly higher concentration of GRs-ir and c-Fos/GR colocalised neurons in the same amygdala nucleus. The pattern of distribution of 5-HT(1A) and GR receptor-ir in LR and HR animals was similar to the c-Fos and GRs-ir expression. LR animals showed a higher density of 5-HT(1A) and GRs-ir in the cortical M2 area and DG as well as an increased number of cells co-expressing 5-HT(1A) and GR-ir in the same brain areas. HR rats had a significantly higher concentration of 5-HT(1A) and GR-ir as well as a greater number of c-Fos/GR protein colocalised neurons in the BLA. The present data add to the arguments for the neurobiological background of differences in individual responses to aversive conditioned stimuli.Behavioural brain research 07/2009; 200(1):150-9. · 3.22 Impact Factor -
Article: The effect of CRF and alpha-helical CRF((9-41)) on rat fear responses and amino acids release in the central nucleus of the amygdala.
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ABSTRACT: The 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. The intracerebroventricular administration of alpha-helical CRF((9-41)) (10 microg/rat) significantly decreased the rat freezing responses and increased the local concentration of GABA during the first 30 min of observation. In sum, these are new findings, which show an important role of CRF in the CeA in the regulation of fear-controlled amino acids release and suggest an involvement of amino acids in the central nucleus of the amygdala in the effects of this neurohormone on the expression of conditioned fear.Neuropharmacology 06/2009; 57(2):148-56. · 4.81 Impact Factor -
Article: The effects of group III mGluR ligands on pentylenetetrazol-induced kindling of seizures and hippocampal amino acids concentration.
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ABSTRACT: 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. It was determined that the kindling of PTZ-induced seizures could be attenuated by post intracerebroventricular administration of 100 nmol of the group III mGluR antagonist CPPG [(RS)-a-cyclopropyl-4-phosphonophenylglycine]. There were significant differences in tested parameters during the final stages of the kindling procedure. The group III mGluR agonist L-AP4 [L-(+)-2-amino-4-phosphonobutyric acid at 100 nmol, i.c.v.] did not significantly affect the kindling of seizures in comparison to control rats, although there was acceleration of the process as compared to CPPG treated animals. We demonstrated that the baseline concentrations of glutamate, GABA, alanine, taurine, and the glutamine/GABA ratio were elevated in the hippocampus of fully kindled rats. Intracerebroventricular administration of a single dose of CPPG increased the concentrations of glutamate in the hippocampus of control, non-kindled rats. Intracerebroventricular administration of L-AP4 did not affect the hippocampal amino acid concentration in either animal group. Overall, these data suggest that there is a shift in the balance between neurotransmitters towards increased production of excitatory amino acids, and this may be mediated by group III mGluRs during seizure kindling.Brain research 06/2009; 1282:20-7. · 2.46 Impact Factor -
Article: Time course of changes in the concentration of kynurenic acid in the brain of pentylenetetrazol-kindled rats.
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ABSTRACT: The 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.p.--the dose used in the kindling experiment, n=7) caused a much less pronounced KYNA depletion, with different structures affected: the nucleus accumbens, piriform cortex and amygdala. The comparison of KYNA concentration in rats subjected to the kindling of seizures with that in animals given a single, proconvulsive, dose of PTZ (55 mg/kg, n=7) showed that the kindling itself, rather than the occurrence of a fit of seizures, was responsible for the depletion of KYNA in the hippocampus and caudate putamen. Another control experiment showed that neither single nor repeated saline injections caused significant changes in KYNA concentration. The data indicate that changes in the brain concentration of an endogenous inhibitory neurotransmitter, KYNA, undergo selective modulation in the course of a kindling of seizures. This suggests that the depletion of KYNA within the hippocampus may be directly related to the development of kindled seizures in this model of epilepsy.Brain research bulletin 12/2008; 78(6):299-305. · 2.18 Impact Factor -
Article: The role of the dorsomedial part of the prefrontal cortex serotonergic innervation in rat responses to the aversively conditioned context: behavioral, biochemical and immunocytochemical studies.
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ABSTRACT: In 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. The LS animals revealed an opposite pattern of behavioral and biochemical changes after serotonergic lesion: an increase in the duration of a freezing response, and expression of c-Fos in the basolateral and central nuclei of amygdala, and a lower GABA concentration in the basolateral amygdala. In control conditions, c-Fos expression did not differ in LS and HS, naïve, not conditioned and not exposed to the test cage animals. The present study adds more arguments for the controlling role of serotonergic innervation of the dorsomedial part of the prefrontal cortex in processing emotional input by other brain centers. Moreover, it provides experimental data, which may help to better explain the anatomical and biochemical basis of differences in individual reactivity to stressful stimulation, and, possibly, to anxiolytic drugs with serotonergic or GABAergic profiles of action.Behavioural Brain Research 11/2008; 192(2):203-15. · 3.42 Impact Factor -
Article: Changes in the concentration of amino acids in the hippocampus of pentylenetetrazole-kindled rats.
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ABSTRACT: It 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. No differences between kindled and not-kindled animals in the glycine, histidine and glutamine levels were present. There also appeared an over fourfold increase of the Glu/GABA ratio, a theoretical marker of the neuronal excitation level, in the kindled animals. A multivariate classification tree analysis showed that the hippocampal concentration of taurine, together with GABA and Glu, had the relatively largest prediction accuracy in discriminating between kindled and non-kindled animals, suggesting a specific role of these amino acids in the shaping of a new equilibrium between excitatory and inhibitory processes in the hippocampus of kindled animals.Neuroscience Letters 08/2008; 439(3):245-9. · 2.11 Impact Factor -
Article: The influence of CRF and alpha-helical CRF(9-41) on rat fear responses, c-Fos and CRF expression, and concentration of amino acids in brain structures.
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ABSTRACT: In 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. A different pattern of behavioral and biochemical changes was present after pre-test administration of alpha-helical CRF((9-41)) (10 microg/rat): a decrease in rat fear response and serum corticosterone concentration; an attenuation of fear-induced c-Fos expression in the dentate gyrus, CA1, Cg1, Cg2, and M1 areas of the frontal cortex; a complete reversal of the rise in the number of CRF immunoreactive complexes in the M2 cortical area, induced by conditioned fear. Moreover, alpha-helical CRF((9-41)) increased the concentration of GABA in the amygdala of fear-conditioned rats. Altogether, the present data confirm and extend previous data on the integrative role of CRF in the central, anxiety-related, behavioral and biochemical processes. The obtained results underline also the role of frontal cortex and amygdala in mediating the effects of CRF on the conditioned fear response.Hormones and Behavior 07/2008; 54(5):602-12. · 3.87 Impact Factor -
Article: Expression of c-Fos and CRF in the brains of rats differing in the strength of a fear response.
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ABSTRACT: The 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. rats with duration of a freezing response one standard error, or more, below the mean value, had a higher activity of the M2 cortical area, and the median raphe nucleus (c-Fox expression), in comparison to the high responders (HR), i.e. rats with the duration of a freezing response one standard error, or more, above the mean value. These animals had also stronger 5-HT- and CRF-related immunostaining in the M2 area, and increased concentration of GABA in the basolateral nucleus of amygdala (in vivo microdialysis). The LR group vocalized more during test session in the aversive band, and had higher serum levels of corticosterone, examined 10 min after test session. It was shown that different natural patterns of responding to conditioned aversive stimuli are associated with different involvement of brain structures and with dissimilar neurochemical mechanisms.Behavioural Brain Research 04/2008; 188(1):154-67. · 3.42 Impact Factor
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Institutions
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2003–2013
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Medical University of Warsaw
- Katedra i Zakład Farmakologii Doświadczalnej i Klinicznej
Warsaw, Masovian Voivodeship, Poland
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2006–2010
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Institute of Psychiatry and Neurology
Warsaw, Masovian Voivodeship, Poland
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