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

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

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

Whole cell patch-clamp recordings from GABAergic cells of thalamic reticular nucleus (RTN) in thalamocortical slices made from postnatal day 6 (P6) to 10 (P10) were used to investigate the pattern of rebound bursts (RBs) triggered by an injection of hyperpolarizing current into RTN cells. The number of RBs in the RTN and the overlying Na+/K+ spikes changed in an agedependent manner. The generation of RBs depended largely on the amplitude of the after-hyperpolarizations (AHPs). RB patterns in response to hyperpolarizing current injection into relay cells were markedly different from RB patterns in RTN cells with an after-depolarization. GABAA receptor antagonist bicuculline methiodide (BMI) changed burst firing patterns, increasing the duration of RB and decreasing the amplitude of AHP in RTN cells. Furthermore, local puffs of NMDA in the presence of BMI induced RBs. K+ channel blocker 4-aminopyridine partially mimicked the effect of BMI on AHPs. The shapes of RBs were altered by a selective CaMKII inhibitor KN-62, but not by an inactive analog KN-04.

• MeSH
• 1-(5-isochinolinsulfonyl)-2-methylpiperazin analogy a deriváty   farmakologie   MeSH
• 4-aminopyridin farmakologie   MeSH
• akční potenciály fyziologie   účinky léků   MeSH
• bikukulin analogy a deriváty   farmakologie   MeSH
• blokátory draslíkových kanálů farmakologie   MeSH
• financování organizované MeSH
• GABA antagonisté farmakologie   MeSH
• GABA fyziologie   MeSH
• inhibitory proteinkinas farmakologie   MeSH
• jádra thalamu cytologie   fyziologie   MeSH
• myši inbrední ICR MeSH
• myši MeSH
• nervový útlum fyziologie   účinky léků   MeSH
• neurony fyziologie   MeSH
• novorozená zvířata MeSH
• orgánové kultury - kultivační techniky MeSH
• proteinkinasa závislá na vápníku a kalmodulinu typ 2 antagonisté a inhibitory   metabolismus   MeSH
• receptory GABA-A - antagonisté MeSH
• receptory GABA-A fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH

• MeSH
• bikukulin aplikace a dávkování   MeSH
• epilepsie patofyziologie   MeSH
• finanční podpora výzkumu jako téma MeSH
• GABA antagonisté terapeutické užití   MeSH
• krysa rodu rattus MeSH
• organofosforové sloučeniny aplikace a dávkování   MeSH
• receptory GABA-A - antagonisté MeSH
• receptory GABA-A účinky léků   MeSH
• receptory GABA-B - antagonisté MeSH
• receptory GABA-B účinky léků   MeSH
• záchvaty patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH

• MeSH
• krysa rodu rattus MeSH
• nucleus suprachiasmaticus fyziologie   MeSH
• receptory GABA-A - antagonisté MeSH
• receptory GABA-A fyziologie   MeSH
• zinek fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH

• MeSH
• benzodiazepiny metabolismus   MeSH
• receptory GABA-A - antagonisté MeSH
• receptory GABA-A metabolismus   MeSH
• vazebná místa MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• biochemie
• farmacie a farmakologie