- MeSH
- antikonvulziva terapeutické užití MeSH
- antipsychotika farmakokinetika škodlivé účinky terapeutické užití MeSH
- dospělí MeSH
- elektroencefalografie * účinky léků MeSH
- klozapin * farmakokinetika škodlivé účinky MeSH
- kombinovaná farmakoterapie MeSH
- lékové interakce MeSH
- lidé MeSH
- paranoidní schizofrenie farmakoterapie komplikace MeSH
- výsledek terapie MeSH
- záchvaty chemicky indukované prevence a kontrola MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- delirium diagnóza MeSH
- duševní poruchy diagnóza MeSH
- elektroencefalografie metody účinky léků MeSH
- elektromyografie klasifikace metody MeSH
- evokované potenciály MeSH
- lidé MeSH
- mozkové vlny MeSH
- nemoci nervového systému diagnóza MeSH
- neurologické vyšetření * klasifikace MeSH
- záchvaty diagnóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Local application of four concentrations of bicuculline methiodide (a specific antagonist of GABA(A) receptors) was used to study a sensitivity of somatosensory cortex in four age groups of immature rats with implanted electrodes. Presence and latencies of two epileptic phenomena (focal discharges and seizures) were evaluated. Focal discharges exhibited moderate tendency to a decrease of sensitivity to bicuculline methiodide with maturation. Concentration-effect relation of incidence of focal discharges was observed only in 7- and 12-day-old but not in older animals. Results with incidence and latencies of seizures did not show relations to age or concentration of bicuculline. Neither of the epileptic phenomena can be used as a reliable index of cortical maturation.
- MeSH
- bikukulin farmakologie terapeutické užití MeSH
- elektroencefalografie účinky léků MeSH
- krysa rodu rattus MeSH
- potkani Wistar MeSH
- receptory GABA-A - antagonisté farmakologie MeSH
- receptory GABA-A fyziologie MeSH
- somatosenzorické korové centrum účinky léků růst a vývoj MeSH
- věkové faktory MeSH
- záchvaty farmakoterapie patofyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
RATIONALE: Disruption of auditory event-related evoked potentials (ERPs) P300 and mismatch negativity (MMN), electrophysiological markers of attentive and pre-attentive cognitive processing, is repeatedly described in psychosis and schizophrenia. Similar findings were observed in a glutamatergic model of psychosis, but the role of serotonergic 5-HT2A receptors in information processing is less clear. OBJECTIVES: We studied ERPs in a serotonergic model of psychosis, induced by psilocybin, a psychedelic with 5-HT2A/C agonistic properties, in healthy volunteers. METHODS: Twenty subjects (10M/10F) were given 0.26 mg/kg of psilocybin orally in a placebo-controlled, double-blind, cross-over design. ERPs (P300, MMN) were registered during the peak of intoxication. Correlations between measured electrophysiological variables and psilocin serum levels and neuropsychological effects were also analyzed. RESULTS: Psilocybin induced robust psychedelic effects and psychotic-like symptoms, decreased P300 amplitude (p = 0.009) but did not affect the MMN. Psilocybin's disruptive effect on P300 correlated with the intensity of the psychedelic state, which was dependent on the psilocin serum levels. We also observed a decrease in N100 amplitude (p = 0.039) in the P300 paradigm and a negative correlation between P300 and MMN amplitude (p = 0.014). CONCLUSIONS: Even though pre-attentive cognition (MMN) was not affected, processing at the early perceptual level (N100) and in higher-order cognition (P300) was significantly disrupted by psilocybin. Our results have implications for the role of 5-HT2A receptors in altered information processing in psychosis and schizophrenia.
- MeSH
- akustická stimulace metody MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- elektroencefalografie účinky léků metody MeSH
- halucinogeny farmakologie MeSH
- klinické křížové studie MeSH
- kognice účinky léků fyziologie MeSH
- kognitivní evokované potenciály P300 účinky léků fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- pozornost účinky léků fyziologie MeSH
- psilocybin škodlivé účinky farmakologie MeSH
- senioři MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky kontrolované MeSH
- práce podpořená grantem MeSH
The period around birth is a risky time for stroke in infants, which is associated with two major acute and subacute processes: anatomical damage and seizures. It is unclear as to what extent each of these processes independently contributes to poor outcome. Furthermore, it is unclear whether there is an interaction between the two processes - does seizure activity cause additional brain damage beyond that produced by ischemia and/or does brain damage foster seizures? The model of focal cerebral ischemia induced by the intrahippocampal infusion of endothelin-1 (ET-1) in 12-day-old rat was used to examine the role of the endothelin receptors in the development of focal ischemia, symptomatic acute seizures and neurodegeneration. ET-1 (40pmol/μl) was infused either alone or co-administered with selective antagonists of ETA (BQ123; 70nmol/μl) or ETB receptors (BQ788; 70nmol/1μl). Effects of activation of ETB receptors were studied using selective agonist 4-Ala-ET-1 (40pmol/1μl). Regional cerebral blood flow (rCBF) and tissue oxygenation (pO2) were measured in anesthetized animals with a Doppler-flowmeter and a pO2-sensor, respectively. Seizure development was assessed with video-EEG in freely moving rats. Controls received the corresponding volume of the appropriate vehicle (10mM PBS or 0.01% DMSO-PBS solution; pH7.4). The extent of hippocampal lesion was determined using FluoroJade B staining performed 24h after ET-1 infusion. Infusion of ET-1 or ET-1+ETB receptor antagonist reduced rCBF to ~25% and pO2 to ~10% for about 1.5h, whereas selective ETB agonist, ET-1+ETA antagonist and the PBS vehicle had only negligible effect on the rCBF and pO2 levels. Reduction of rCBF was associated with the development of lesion in the injected hippocampus. In all groups, except sham operated and PBS controls, epileptiform activity was observed after activation of the ETA or the ETB receptors. The data revealed a positive correlation between the severity of morphological damage and all the measured seizure parameters (seizure frequency, average and total seizure duration) in the ET-1 group. In addition, the severity of morphological damage positively correlated with the average seizure duration in animals after infusion of ET-1+ETA receptor antagonist or after infusion of ET-1+ETB receptor antagonist. Our results indicate that the activation of ETA receptors is crucial for ischemia development, however either ETA or ETB receptors mediate the development of seizures following the application of ET-1 in immature rats. The dissociation between the ischemic-producing and seizure-producing processes suggests that damage is not necessary to induce seizures, although it may exacerbate them.
- MeSH
- elektroencefalografie * účinky léků MeSH
- endotelin-1 aplikace a dávkování toxicita MeSH
- hipokampus účinky léků metabolismus MeSH
- injekce intraventrikulární MeSH
- krysa rodu rattus MeSH
- potkani Wistar MeSH
- receptor endotelinu A agonisté metabolismus MeSH
- receptor endotelinu B agonisté metabolismus MeSH
- záchvaty chemicky indukované metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In the present study we investigated the potential antipsychotic effects of the mGlu2/3 agonist LY379268 on changes in EEG power spectra and coherence in the ketamine model of psychosis. In order to use behaviorally active drug doses, experiments detecting changes in locomotor activity and sensorimotor gating were also conducted. In EEG experiments, adult male Wistar rats were injected with ketamine 30 mg/kg i.p. and LY379268 3 mg/kg i.p. Cortical EEG was recorded from twelve (2 × 6) electrodes placed homolaterally on each hemisphere. To avoid interference with the behavioral hyperactivity of ketamine challenge, the behavioral activity of animals was simultaneously registered at the time of recording. Subsequent power spectral and coherence analyses were assessed in epochs corresponding to behavioral inactivity. Analysis of segments with behavioral activity compared to inactivity was also performed. The effects of LY379268 3 mg/kg i.p. on the deficits in sensorimotor processing and on hyperlocomotion induced by ketamine were evaluated in the test of prepulse inhibition of acoustic startle reaction (PPI ASR) and in the open field. LY379268 reversed the ketamine-induced hyperlocomotion but had no effect on ketamine-induced PPI deficits. In EEG epochs corresponding to behavioral inactivity ketamine decreased the power in the delta band, induced a power increase in the high frequency bands and globally decreased EEG coherence. Pretreatment with the LY379268 completely reversed the ketamine-induced power increase in high frequency bands and had a partial effect on EEG coherence. LY379268 alone induced a decrease of beta, high beta and low-gamma power, and an increase in coherence in high frequency bands. Additional analysis revealed that behavioral activity increases power as well as coherence in most frequency bands. In conclusion, agonism of mGlu2/3 receptors was effective in reversing most of the changes induced by ketamine, however due to the lack of effectiveness on PPI deficits its potential antipsychotic properties remain disputable.
- MeSH
- aminokyseliny farmakologie terapeutické užití MeSH
- antipsychotika farmakologie terapeutické užití MeSH
- bicyklické sloučeniny heterocyklické farmakologie terapeutické užití MeSH
- elektroencefalografie účinky léků metody MeSH
- ketamin toxicita MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech * MeSH
- potkani Wistar MeSH
- psychotické poruchy farmakoterapie patofyziologie MeSH
- receptory metabotropního glutamátu agonisté MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Activation of GABA(B) receptors leads to longer inhibitory postsynaptic potentials than activation of GABA(A) receptors. Therefore GABA(B) receptors may be a target for anticonvulsant therapy. The present study examined possible effects of GABA(B) receptor agonist SKF97541 on cortical and hippocampal epileptic afterdischarges (ADs). Epileptic ADs elicited by electrical stimulation of sensorimotor cortex or dorsal hippocampus were studied in adult male Wistar rats. Stimulation series were applied 6 times with 10- or 20-min interval. Either interval was efficient for reliable elicitation of cortical ADs but stimulation at 10-min intervals did not reliably elicit hippocampal ADs, many stimulations were without effect. SKF97541 in dose 1 mg/kg significantly prolonged cortical ADs. Duration of hippocampal ADs was not significantly changed by either dose of SKF97541 in spite of a marked myorelaxant effect of the higher dose. Our present data demonstrated that neither cortical nor hippocampal ADs in adult rats were suppressed by GABA(B) receptor agonist SKF97541. Proconvulsant effect on cortical ADs indicates a different role in these two brain structures. In addition, duration of refractory period for electrically-induced ADs in these two structures in adult rats is different.
- MeSH
- elektroencefalografie účinky léků MeSH
- epilepsie patofyziologie MeSH
- hipokampus patofyziologie MeSH
- krysa rodu rattus MeSH
- mozková kůra patofyziologie MeSH
- organofosforové sloučeniny farmakologie MeSH
- potkani Wistar MeSH
- pyramidové buňky účinky léků MeSH
- receptory GABA-B - agonisté farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The present study examined whether status epilepticus (SE) induced by LiCl-pilocarpine in immature rats (postnatal day [P]12) interferes with normal development; leads to progressive epileptogenesis, or cognitive decline and to pathology similar to that seen in human temporal lobe epilepsy. We correlated the extent of pathologic changes with the severity of functional alterations or epilepsy. SE-induced changes were compared with those of rats with SE induced at P25. Animals of both ages were exposed to a battery of behavioral tests for up to 3months after SE. Rats with SE at P12 showed mild retardation of psychomotor development and delayed habituation, whereas rats with SE at P25 showed no habituation. Assessment in adulthood using the Morris water maze test revealed that SE at both P12 and P25 led to cognitive impairment and that the severity of the impairment increased with age. A handling test revealed increased aggression in rats with SE at P25, but not in rats with SE at P12. Epilepsy was diagnosed with continuous video-electroencephalographic (EEG) monitoring for up to 7d. P25 rats were monitored at 5months after SE and seizures were detected in 83.3% of animals. P12 animals were divided into two groups and monitored at 5 or 7months after SE. Both the severity and incidence of spontaneous recurrent seizures tended to progress with time, and their incidence increased from 50% to 87.5% at 5 and 7months, respectively. Morphometric analysis and stereologic assessment of hilar neurons performed after video-EEG monitoring revealed atrophy of temporal brain structures, enlargement of lateral ventricles, and loss of hilar neurons in both age groups. In P12 rats, morphologic damage also tended to progress over time. Performance of animals in the Morris water maze correlated with the severity of damage, but not with seizure parameters.
- MeSH
- agonisté muskarinových receptorů MeSH
- agrese psychologie MeSH
- antimanika MeSH
- atrofie MeSH
- bludiště - učení účinky léků MeSH
- chlorid lithný MeSH
- chování zvířat fyziologie MeSH
- elektroencefalografie účinky léků MeSH
- hipokampus patologie MeSH
- kognitivní poruchy etiologie psychologie MeSH
- krysa rodu rattus MeSH
- mozek patologie MeSH
- mozkové komory patologie MeSH
- novorozená zvířata MeSH
- pilokarpin MeSH
- pohybová aktivita účinky léků MeSH
- potkani Wistar MeSH
- progrese nemoci MeSH
- psychomotorický výkon fyziologie MeSH
- stárnutí fyziologie MeSH
- status epilepticus chemicky indukované patologie psychologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Pro schizofrenii jsou charakteristické změny jak v kvantitativním EEG, tak i významný deficit v senzorimotorickém zpracování. Cílem této práce bylo srovnat vliv tryptaminového (psilocin) a fenyletylaminového (mezkalin) halucinogenu v animálním modelu psychózy. Testovali jsme senzomotorické zpracování informací a vliv na funkční konektivitu mozku pomocí kvantitativního EEG (qEEG). EEG záznam jsme registro¬ vali ze 12 subdurálních elektrod umístěných nad homologními částmi frontální, motorické, parietální a temporální mozkové kůry u volně se pohybujících potkanů. Obě látky narušily senzorimotorické zpracování informací a z hlediska qEEG indukovaly deficit ve funkční konektivitě. Tento deficit se projevoval jak snížením EEG výkonu napříč spektrem, a tak i snížením EEG koherencí. Naše data vykazují značnou podobnost s nálezy u nemocných schizofrenií, což vypovídá o validitě použitých modelů.
Deficits in senzorimotor information processing as well as some changes in quantitative EEG (qEEG) are characteristic for schiz ophrenia. This study focuses on a comparision of two hallucinogens, tryptamine (psilocin) and phenylethylamine (meskaline), in an animal model of psychosis. The registration of qEEG was performed from 12 subdural electrodes placed on six homologous sites of frontal, motor, parietal and temporal cortex in freely moving rats. Both substances disrupted senzorimotor information processing as well as they both decre ased functio- nal connectivity in qEEG (i.e. decrease in power spectra and coherence). Our data are similar to findings of schizophrenia pati ents, confirming validity of used models.
- Klíčová slova
- prepulzní inhibice úlekové reakce, EEG koherence, EEG spektra, potkan,
- MeSH
- elektroencefalografie statistika a číselné údaje účinky léků MeSH
- experimenty na zvířatech MeSH
- financování organizované MeSH
- krysa rodu rattus MeSH
- lokomoce účinky léků MeSH
- meskalin aplikace a dávkování MeSH
- modely nemocí na zvířatech MeSH
- mozek patofyziologie účinky léků MeSH
- potkani Wistar MeSH
- psilocybin analogy a deriváty aplikace a dávkování MeSH
- schizofrenie patofyziologie MeSH
- sluchová percepce fyziologie účinky léků MeSH
- úleková reakce účinky léků MeSH
- výzkum metody statistika a číselné údaje MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH