Among neurotransmitter systems affected by status epilepticus (SE) in adult rats are both GABAergic systems. To analyze possible changes of GABAA and GABAB systems in developing rats lithium-pilocarpine SE was induced at postnatal day 12 (P12). Seizures were elicited by a GABAA antagonist pentylenetetrazol (PTZ) 3, 6, 9, and 13 days after SE (i.e., in P15, P18, P21, and P25 rats), and their possible potentiation by a GABAB receptor antagonist CGP46381 was studied. Pilocarpine was replaced by saline in control animals (lithium-paraldehyde [LiPAR]). Pentylenetetrazol in a dose of 50 mg/kg s.c. elicited generalized seizures in nearly all 15-day-old naive rats and in 40% of 18-day-old ones but not in older animals. After SE, PTZ no longer elicited seizures in these two younger groups, i.e., sensitivity of GABAA system was diminished. The GABAB antagonist exhibited proconvulsant effect in P15 and P18 SE as well as LiPAR rats returning the incidence of PTZ-induced seizures to values of control animals. A decrease in the incidence of minimal clonic seizures was seen in P21 LiPAR animals; these seizures in the oldest group were not affected. Change of the effect from proconvulsant to anticonvulsant (or at least to no action) took place before postnatal day 21. Both SE and LiPAR animals exhibited similar changes but their intensity differed, effects in LiPAR controls were usually more expressed than in SE rats.
- MeSH
- antikonvulziva terapeutické užití MeSH
- krysa rodu rattus MeSH
- kyseliny fosfinové škodlivé účinky metabolismus MeSH
- lékové interakce fyziologie MeSH
- novorozená zvířata MeSH
- pentylentetrazol škodlivé účinky MeSH
- potkani Wistar MeSH
- receptory GABA-A - antagonisté metabolismus MeSH
- receptory GABA-B - antagonisté škodlivé účinky metabolismus MeSH
- status epilepticus chemicky indukované farmakoterapie metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Possible proconvulsant action of GABAB receptor antagonist CGP46381 was studied 3 and 13 days after status epilepticus elicited in 12-day-old rats. GABAA-dependent activity was tested by pentylenetetrazol administration and found different in 15-day-old rats after status epiolepticus but not in the older group. The interaction of the two GABAergic systems should be studied in detail.
- MeSH
- konvulzíva terapeutické užití MeSH
- krysa rodu rattus MeSH
- kyseliny fosfinové terapeutické užití MeSH
- modely nemocí na zvířatech MeSH
- novorozená zvířata MeSH
- pentylentetrazol toxicita MeSH
- pilokarpin toxicita MeSH
- potkani Wistar MeSH
- receptory GABA-B - antagonisté terapeutické užití MeSH
- status epilepticus chemicky indukované farmakoterapie MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem 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
Salusin-beta is newly identified bioactive peptide of 20 amino acids, which is widely distributed in hematopoietic system, endocrine system, and the central nervous system (CNS). Although salusin-beta extensively expressed in the CNS, the central cardiovascular functions of salusin-beta are unclear. Our main objective was to determine the cardiovascular effect of microinjection of salusin-beta into the nucleus tractus solitarii (NTS) in anesthetized rats. Bilateral or unilateral microinjection of salusin-beta (0.94-94 microg/rat) into the NTS dose-dependently decreased blood pressure and heart rate. Bilateral NTS microinjection of salusin-beta (9.4 microg/rat) did not alter baroreflex sensitivity. Prior application of the glutamate receptor antagonist kynurenic acid (0.19 microg/rat, n=9) into the NTS did not alter the salusin-beta (9.4 microg/rat) induced hypotension and bradycardia. However, pretreatment with the GABA receptor agonist muscimol (0.5 ng/rat) within the rostral ventrolateral medulla (RVLM) completely abolished the hypotension (-14+/-5 vs. -3+/-5 mm Hg, P<0.05) and bradycardia (-22+/-6 vs. -6+/-5 bpm, P<0.05) evoked by intra-NTS salusin-beta (9.4 microg/rat). In addition, we found that vagotomy didn't influence the actions of salusin-beta (9.4 microg/rat) in the NTS. In conclusion, our present study shows that microinjection of salusin-beta into the NTS significantly produces hypotension and bradycardia, presumably by suppressing the activities of presympathetic neurons in the RVLM.
- MeSH
- antagonisté excitačních aminokyselin farmakologie MeSH
- baroreflex účinky léků MeSH
- bradykardie chemicky indukované patofyziologie MeSH
- GABA antagonisté farmakologie MeSH
- hemodynamika účinky léků MeSH
- hypotenze chemicky indukované patofyziologie MeSH
- krysa rodu rattus MeSH
- kyselina kynurenová farmakologie MeSH
- medulla oblongata cytologie účinky léků MeSH
- mezibuněčné signální peptidy a proteiny aplikace a dávkování farmakologie MeSH
- mikroinjekce MeSH
- muscimol farmakologie MeSH
- neurony účinky léků MeSH
- nucleus solitarius účinky léků MeSH
- potkani Sprague-Dawley MeSH
- sympatický nervový systém účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Postictal refractoriness may be taken as an expression of lasting activity of inhibitory systems arresting seizures. We tested drugs interfering with GABAergic inhibitory system in pairs of cortical epileptic afterdischarges induced with 1-min interval in rats. Under control conditions the second stimulation failed to elicit an afterdischarge. This postictal refractoriness was not affected by antagonists of GABAA receptors acting at three binding sites (bicuculline, picrotoxin, benzodiazepine inverse agonist Ro 19-4603) as well as by a less specific antagonist pentetrazol. In contrast, antagonist of GABAB receptors CGP35348 partially blocked the refractoriness. Cooperation of different inhibitory systems is probably necessary to abolish postictal refractoriness in neocortex. This article is part of the Special Issue entitled 'GABAergic Signaling in Health and Disease'.
- MeSH
- azepiny farmakologie MeSH
- bikukulin farmakologie MeSH
- elektrická stimulace MeSH
- epilepsie farmakoterapie patofyziologie MeSH
- implantované elektrody MeSH
- mozková kůra účinky léků patofyziologie MeSH
- organofosforové sloučeniny farmakologie MeSH
- pentylentetrazol farmakologie MeSH
- pikrotoxin farmakologie MeSH
- potkani Wistar MeSH
- receptory GABA-A - antagonisté farmakologie MeSH
- receptory GABA-A metabolismus MeSH
- receptory GABA-B - antagonisté farmakologie MeSH
- receptory GABA-B metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Benzodiazepines have been widely used in clinical praxis for many decades. They act as GABAA receptor agonists and possess muscle-relaxant, hypnotic-sedative, anticonvulsant, and anxiolytic properties. Flumazenil acts as a benzodiazepine receptor antagonist (subunits α1, α2, α3, and α5) or partial agonist (subunits α4 and α6). It competitively inhibits the activity at the benzodiazepine recognition site on the GABA/benzodiazepine receptor complex, thereby reversing the effects of benzodiazepines. In our experiments, administration of flumazenil in rabbits was surprisingly associated with anxiolytic effects similar to those of midazolam. Additionally, flumazenil significantly and dose-dependently decreased the total number of vocalizations in rats, i.e. it was anxiolytic. These observations seem to be in contrast to the effect of flumazenil in humans, where it is believed to produce mainly anxiogenic effects. It seems that in individuals, who exhibit anxiogenic behavior or in individuals with anticipation anxiety, flumazenil acts as an anxiolytic agent, while in individuals without any signs of anxiety, flumazenil can also act as anxiogenic agent. Thus, we hypothesize that flumazenil is associated with decreased intensity of anticipatory anxiety due to occupancy of benzodiazepine binding sites by an endogenous ligand with inverse agonistic properties.
- MeSH
- anxiolytika aplikace a dávkování farmakologie MeSH
- benzodiazepiny antagonisté a inhibitory metabolismus MeSH
- biologické modely * MeSH
- flumazenil aplikace a dávkování farmakologie MeSH
- králíci MeSH
- lidé MeSH
- ligandy MeSH
- receptory GABA-A - antagonisté aplikace a dávkování farmakologie MeSH
- úzkost farmakoterapie MeSH
- vazebná místa MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Rat hippocampus plays a crucial role in many spatial tasks, including recognition of position of objects, which can be approached and explored. Whether hippocampus is also necessary for recognizing positions of objects located in an inaccessible part of the environment remains unclear. To address this question, we conditioned rats to press a lever when an object displayed on a distant computer screen was in a particular position ("reward position") and not to press the lever when the object was in other positions ("nonreward positions"). After the rats had reached an asymptotic performance, the role of the dorsal hippocampus was assessed by blocking its activity with muscimol. The rats without functional dorsal hippocampus did not discriminate the reward position from the nonreward positions. Then the same rats were trained to discriminate light and dark conditions. The hippocampal inactivation did not disrupt the ability to discriminate these two conditions. It indicated that the inactivation itself had no major effect on the operant behavior and its control by visual stimuli. We conclude that rats use dorsal hippocampus for recognizing positions of objects located in an inaccessible part of the environment.
- MeSH
- chování zvířat fyziologie MeSH
- diskriminace (psychologie) účinky léků fyziologie MeSH
- hipokampus účinky léků fyziologie MeSH
- krysa rodu rattus MeSH
- muscimol farmakologie MeSH
- operantní podmiňování MeSH
- potkani Long-Evans MeSH
- receptory GABA-A - antagonisté farmakologie MeSH
- rozpoznávání (psychologie) účinky léků fyziologie MeSH
- vnímání prostoru účinky léků fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Antagonists of GABA(B) receptors are expected to have proconvulsant action also in developing brain. Two antagonists (CGP55845 and CGP46381) were tested in a model of cortical epileptic afterdischarges (ADs) in 12-, 18- and 25-day-old rat pups with implanted electrodes. CGP55845 was dissolved in dimethylsulfoxide and the results demonstrated marked proconvulsant action of this solvent which masked possible action of the antagonist. Water soluble antagonist CGP46381 led to marked potentiation of ADs in 12-day-old animals, its action decreased with age, it was negligible in 25-day-old rats. Our results demonstrated important inhibitory role of GABA(B) receptors at very early stages of maturation.
- MeSH
- akční potenciály účinky léků MeSH
- elektroencefalografie MeSH
- epilepsie myoklonické chemicky indukované patofyziologie MeSH
- injekce intraperitoneální MeSH
- konvulzíva MeSH
- krysa rodu rattus MeSH
- kyseliny fosfinové farmakologie MeSH
- modely nemocí na zvířatech * MeSH
- mozková kůra účinky léků patofyziologie MeSH
- potkani Wistar MeSH
- propanolaminy farmakologie MeSH
- receptory GABA-B - antagonisté farmakologie MeSH
- receptory GABA fyziologie MeSH
- stárnutí MeSH
- synergismus léků MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Cortical epileptic foci elicited by local application of bicuculline methiodide represent a model of interictal epileptic activity with a transition into ictal phases. We studied a role of GABA-B receptors in this model using GABA-B receptor antagonist CGP35348 in adult rats with implanted cortical electrodes and cannula. CGP35348 (100 or 200 mg/kg i.p.) did not affect interictal discharges but it augmented ictal activity. Latency to the first ictal episode was decreased by the lower dose of CGP35348, duration of episodes was increased by the higher dose. GABA-B receptor antagonist did not influence purely cortical epileptic phenomenon but it is proconvulsant in ictal activity generated with participation of subcortical structures.
- MeSH
- bikukulin analogy a deriváty MeSH
- časové faktory MeSH
- elektroencefalografie MeSH
- epilepsie chemicky indukované metabolismus patofyziologie MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- mozková kůra metabolismus patofyziologie účinky léků MeSH
- mozkové vlny účinky léků MeSH
- organofosforové sloučeniny toxicita MeSH
- potkani Wistar MeSH
- reakční čas účinky léků MeSH
- receptory GABA-B - antagonisté toxicita MeSH
- receptory GABA-B metabolismus účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The role of inhibitory γ-aminobutyric acid-A (GABA-A) system in the cortical epileptic afterdischarges (ADs) was studied at three different developmental stages of rats. Animals 12, 18 and 25days old with implanted epidural electrodes were pretreated with bicuculline (1 and 2mg/kgi.p.) and 15min later repeatedly stimulated with low frequency trains with stepwise increasing current intensity. Bicuculline only exceptionally decreased threshold current intensities necessary for elicitation of movements directly bound to stimulation, spike-and wave ADs, clonic seizures and transition into a limbic type of ADs. Duration of ADs was not systematically affected by either dose of bicuculline. In contrast, transcallosal evoked potentials exhibited under the influence of bicuculline steeper curve expressing relation between intensity of stimuli and amplitude of responses. In contrast to GABA-B receptors, GABA-A receptors do not play an important role in generation and arrest of cortical epileptic ADs in immature rats.
- MeSH
- bikukulin farmakologie MeSH
- elektrická stimulace MeSH
- evokované potenciály účinky léků fyziologie MeSH
- GABA antagonisté farmakologie MeSH
- implantované elektrody MeSH
- krysa rodu rattus MeSH
- mozková kůra účinky léků patofyziologie MeSH
- potkani Wistar MeSH
- receptory GABA-A fyziologie MeSH
- záchvaty patofyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH