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
- GABA-A Receptor Antagonists metabolism MeSH
- GABA-B Receptor Antagonists adverse effects metabolism MeSH
- Anticonvulsants therapeutic use MeSH
- Rats MeSH
- Phosphinic Acids adverse effects metabolism MeSH
- Drug Interactions physiology MeSH
- Animals, Newborn MeSH
- Pentylenetetrazole adverse effects MeSH
- Rats, Wistar MeSH
- Status Epilepticus chemically induced drug therapy metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't 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
- GABA-A Receptor Antagonists pharmacology MeSH
- Bicuculline pharmacology therapeutic use MeSH
- Electroencephalography drug effects MeSH
- Rats MeSH
- Rats, Wistar MeSH
- Receptors, GABA-A physiology MeSH
- Somatosensory Cortex drug effects growth & development MeSH
- Age Factors MeSH
- Seizures drug therapy physiopathology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article 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
- GABA-A Receptor Antagonists pharmacology MeSH
- GABA-B Receptor Antagonists pharmacology MeSH
- Azepines pharmacology MeSH
- Bicuculline pharmacology MeSH
- Electric Stimulation MeSH
- Epilepsy drug therapy physiopathology MeSH
- Electrodes, Implanted MeSH
- Cerebral Cortex drug effects physiopathology MeSH
- Organophosphorus Compounds pharmacology MeSH
- Pentylenetetrazole pharmacology MeSH
- Picrotoxin pharmacology MeSH
- Rats, Wistar MeSH
- Receptors, GABA-A metabolism MeSH
- Receptors, GABA-B metabolism MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't 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
- GABA-A Receptor Antagonists administration & dosage pharmacology MeSH
- Anti-Anxiety Agents administration & dosage pharmacology MeSH
- Benzodiazepines antagonists & inhibitors metabolism MeSH
- Models, Biological * MeSH
- Flumazenil administration & dosage pharmacology MeSH
- Rabbits MeSH
- Humans MeSH
- Ligands MeSH
- Anxiety drug therapy MeSH
- Binding Sites MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't 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
- GABA-A Receptor Antagonists pharmacology MeSH
- Behavior, Animal physiology MeSH
- Discrimination, Psychological drug effects physiology MeSH
- Hippocampus drug effects physiology MeSH
- Rats MeSH
- Muscimol pharmacology MeSH
- Conditioning, Operant MeSH
- Rats, Long-Evans MeSH
- Recognition, Psychology drug effects physiology MeSH
- Space Perception drug effects physiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't 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-Isoquinolinesulfonyl)-2-Methylpiperazine analogs & derivatives pharmacology MeSH
- 4-Aminopyridine pharmacology MeSH
- Action Potentials physiology drug effects MeSH
- GABA-A Receptor Antagonists MeSH
- Bicuculline analogs & derivatives pharmacology MeSH
- Potassium Channel Blockers pharmacology MeSH
- Financing, Organized MeSH
- GABA Antagonists pharmacology MeSH
- gamma-Aminobutyric Acid physiology MeSH
- Protein Kinase Inhibitors pharmacology MeSH
- Thalamic Nuclei cytology physiology MeSH
- Mice, Inbred ICR MeSH
- Mice MeSH
- Neural Inhibition physiology drug effects MeSH
- Neurons physiology MeSH
- Animals, Newborn MeSH
- Organ Culture Techniques MeSH
- Calcium-Calmodulin-Dependent Protein Kinase Type 2 antagonists & inhibitors metabolism MeSH
- Receptors, GABA-A physiology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- MeSH
- GABA-A Receptor Antagonists MeSH
- GABA-B Receptor Antagonists MeSH
- Bicuculline administration & dosage MeSH
- Epilepsy physiopathology MeSH
- Research Support as Topic MeSH
- GABA Antagonists therapeutic use MeSH
- Rats MeSH
- Organophosphorus Compounds administration & dosage MeSH
- Receptors, GABA-A drug effects MeSH
- Receptors, GABA-B drug effects MeSH
- Seizures physiopathology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
304 s. : il. ; 24 cm
