The change of picrotoxin-induced epileptiform discharges to the beta oscillation by carbachol in rat hippocampal slices The study aimed to determine whether and how the activation of the acetylcholine receptor affects epileptiform discharges in the CA3 region in a rat hippocampus. Picrotoxin (100 μM), a GABA receptor antagonist, was applied to a hippocampal slice to induce epileptiform
by picrotoxin, although the temperature-induced change in frequency recovered to control levels. Overall, these data suggest that I plays an important role in maintaining smooth transitory responses and persistent frequency increases by different mechanisms in the pyloric circuitry during temperature fluctuations.
), are moderately increased in specific brain regions of patients with AD. We provide experimental evidence that TREM2 alternatively spliced isoforms are translated and secreted as sTREM2. Furthermore, our functional analysis reveals that all sTREM2 species inhibit LTP induction, and this effect is abolished by the GABAA receptor antagonist picrotoxin. TREM2 transcripts can give rise to a heterogeneous pool
modulation of the GABA receptor by HK4 was determined by patch clamp in HEK-293 cells, calcium influx in INS-1E cells and by using the specific GABA channel blockers picrotoxin and tert-butylbicyclophosphorothionate (TBPS) in HepG2 cells. Apoptosis was analysed using caspase 3/7, terminal deoxynucleotidyl transferase-dUTP nick end labelling (TUNEL) and array assays in HepG2 cells and/or human primary hepatocytes. Phosphorylation of STAT3 and the NF-κB subunit p65, protein disulphide isomerase (PDI) and poly-ADP-ribose polymerase-1 (PARP-1) was detected by Western blotting. Patch clamping, calcium influx measurements and apoptosis assays with the non-competitive GABA channel blockers picrotoxin and TBPS proved HK4 as a selective positive allosteric modulator of the GABA receptor. In HepG2 cells, which
were then selected to prepare the hydroethanolic extract and its anticonvulsant effect against PTZ at the doses of 122.5, 245 and 490 mg/kg, as well as its acute toxicity were compared with those of the aqueous lyophilisate of the leaves. The anticonvulsant effect of the aqueous lyophilisate of M. arboreus leaves was further evaluated on models of acute epileptic seizures induced by picrotoxin (PIC
effect using formalin test in murine model. Also, the ambulatory effect of the HEX and DHS was determined in Open field test. The possible mechanism of action of DHS was explored in the presence of naltrexone (NTX, 1 mg/kg, i.p.), and picrotoxin (PTX, 1 mg/kg, i.p.). Gastric damage as possible adverse effect or gastroprotection were also investigated. Whereas DHS acute toxicological study was done
to action potentials, they differ from excitatory synapses in both structure and function. Therefore, we hypothesized that inhibitory synapses may have different organizing principles. We report picrotoxin, a GABAR antagonist, blocks neurotransmission in a use-dependent manner at rat hippocampal synapses and therefore can be used to interrogate synaptic properties. Using this tool, we uncovered partial
groups, respectively. The latency to convulsion was prolonged significantly in the metreleptin 10 mg/kg group compared with the vehicle group. Tonic convulsion was observed in 0, 3, 0, 1, and 2 mice, respectively. Pentylenetetrazole (45 mg/kg) was administered subcutaneously in a similar manner and anticonvulsive effect was examined using picrotoxin (3 mg/kg) as the positive
' endocrine conditions were: a) Low hormone levels (rats in diestrus I and II phases); b) High hormone levels (proestrus/estrus phases); c) No hormones (ovariectomized rats); and d) Rats under progesterone withdrawal (PW). To evaluate the participation of the GABA receptor in the anxiolytic-like action of MT the antagonist picrotoxin was used. Results showed that MT induced dose-dependent anxiolytic-like actions in rats with low hormone level conditions. Also, MT reduced anxiety-like behavior in female rats under PW, in contrast to diazepam which was ineffective. MT's anxiolytic-like effect was blocked by picrotoxin, suggesting the participation of the GABA receptor complex. However, increased anxiety-like behavior was observed in rats with a high hormone level condition and low doses of MT. Beneficial
, AM630). CBR-mediated inhibition in VTA DA neuron firing can be mimicked by M-current opener (10 μM retigabine) and blocked by M-current blocker (30 μM XE991). In addition, enhancement of neuronal cAMP by forskolin (10 μM) reduced M-current and increased DA neuron firing rate. Finally, pharmacological block of synaptic transmission by NBQX (10 μM), D-APV (50 μM) and picrotoxin (100 μM) in VTA slices
picrotoxin abolished the protection afforded by the progestins in vivo and in vitro. For the first time, here, we delineate a potential role of desogestrel and drospirenone, both clinically approved and safe drugs in mitigating the consequences of stroke. Contraception with desogestrel and drospirenone in progestin-only preparations may be particularly beneficial for women at risk of stroke.
. Additionally, inward currents caused by SS in hippocampal CA1 neurons was partially blocked by the GABA receptor antagonist picrotoxin (50 μM), suggesting that SS acts on synaptic/extrasynaptic GABA receptors. These findings indicate that SS may function in a way that is similar to nootropic drugs by inhibiting cholinergic abnormalities, and neuronal apoptosis targets and ultimately increasing the expression
expression in the hindbrain and spinal cord; a finding consistent with the reported expression of GlyR subunits in these tissues from other organisms. Electrophysiological recordings using oocytes revealed that all five α subunits form homomeric receptors activated by glycine, and inhibited by strychnine and picrotoxin. In contrast, ß subunits only formed functional heteromeric receptors when co-expressed with α subunits. Curiously, the second transmembranes of both ß subunits were found to lack a phenylalanine at the sixth position that is commonly associated with conferring picrotoxin resistance to heteromeric receptors. Consistent with the absence of phenylalanines at the sixth position, heteromeric zGlyRs often lacked significant picrotoxin resistance. Subsequent efforts revealed that resistance
levels. Then, we assessed LTP induced by four HFS (4xHFS) and found that this form of LTP was significantly depressed in Ts65Dn slices when compared with LTP in euploid control slices. Memantine, however, did not rescue this phenotype. Because 4xHFS-induced LTP had not yet been characterized in Ts65Dn mice, we also investigated the effects of picrotoxin, amyloid beta oligomers, and soluble recombinant human prion protein (rPrP) on this form of LTP. Whereas ≥10 M picrotoxin increased LTP to control levels, it also caused seizure-like oscillations. Neither amyloid beta oligomers nor rPrP had any effect on 4xHFS-induced LTP in Ts65Dn-derived slices.
. Here we investigated the effect of BAD manipulation on K channel activity and excitability in acute brain slices. We found that BAD's influence on neuronal K channels was cell-autonomous and directly affected dentate granule neuron (DGN) excitability. To investigate the role of neuronal K channels in the anticonvulsant effects of BAD, we imaged calcium during picrotoxin-induced epileptiform activity
, but not by picrotoxin, a type A gamma-aminobutyric acid receptor antagonist. The results indicate that KRG activates non-NMDA glutamate receptors of PVN neurons in mice, suggesting that KRG may be a candidate for use in regulation of stress responses by controlling autonomic nervous system and hormone secretion.
of A. aspera methanolic root extract using acute anticonvulsant models and to evaluate the acute toxicity and neurotoxic potential A. aspera extract. A. aspera methanolic extract was standardized with respect to betaine using HPTLC. The maximal electroshock (MES), pentylenetetrazol (PTZ), picrotoxin and bicuculline induced seizure models were used to evaluate the anticonvulsant potential of standardized A. aspera root extract. The GABA content in cortex and hippocampus of extract treated mice was evaluated using HPLC. Moreover, the animals were also evaluated for acute toxicity study and neurotoxicity test. A significant enhancement in the seizure threshold was observed by A. aspera extract (5 and 10mg/kg) treated mice in PTZ, picrotoxin and bicuculline models as compared to saline treated mice
. The anxiolytic-like effect was evaluated using the Burying Behavior Test (BBT) and the Elevated Plus-Maze Test (PMT). The antidepressant-like effect was evaluated in the Forced Swimming Test (FST), and ambulatory activity was assessed in the Open Field Test (OFT). Employing the behavioral tests, synergism and antagonism experiments with Alprazolam, Muscimol, and Picrotoxin were carried out in the PMT
leaf extract (PME) as well as possible mechanism(s) of action in animal models. Effects of PME was assessed in electroconvulsive (the maximal electroshock and 6-Hz seizures) and chemoconvulsive (pentylenetetrazole-, picrotoxin-, isoniazid-, 4-aminopyridine-, and strychnine-induced seizures) models of epilepsy. In addition, effect of the extract on the nitric oxide pathway and GABA receptor complex was evaluated. The extract (30, 100 and 300mgkg, p.o.) significantly delayed the onset as well as decreased the duration and frequency of pentylenetetrazole-, picrotoxin- and strychnine-induced seizures. In addition, PME pre-treatment significantly improved survival in the 4-aminopyridine- and isoniazid-induced seizure tests. Furthermore, the extract protected against 6-Hz psychomotor seizures but had