4'-Ethynyl-4-n-[2,3-3H2]propylbicycloorthobenzoate ([3H]EBOB) binding to the GABAA receptor complex was characterized autoradiographically in rat brain and then its binding in human brain was investigated. [3H]EBOB binding was saturable, specific and identified a single population of binding sites. The Kd obtained from saturation studies was 4.59 nM. Picrotoxin produced dose-dependent inhibitio...

Benzodiazepines are the current first-line standard-of-care treatment for status epilepticus but fail to terminate seizures in about one third of cases. Synaptic GABAA receptors, which mediate phasic inhibition in central circuits, are the molecular target of benzodiazepines. As status epilepticus progresses, these receptors are internalized and become functionally inactivated, conferring benzo...

Dopamine is a critical neuromodulator that activates GPCRs in mammals or ligand-gated ion channels in invertebrates. The present study demonstrates that dopamine (0.1-10 mm) exerts novel, opposing effects on different populations of mammalian (rat) GABAA receptors. Using whole-cell patch-clamp electrophysiology, we observed direct dopamine-mediated inhibition of tonic-level (1 μm) GABA-evoked c...

We assessed the contribution of GABAa and GABAc receptors to GABAergic effects on b- and d-wave in frog ERG in a wide range of light stimulation conditions. The amplitude of both b- and d-wave was increased during GABAa receptor blockade by bicuculline as well as during additional GABAc receptor blockade by picrotoxin. The effects of GABAa receptor blockade were more pronounced in light adaptat...

Atomic resolution structures of cys-loop receptors, including one of a γ-aminobutyric acid type A receptor (GABAA receptor) subtype, allow amazing insights into the structural features and conformational changes that these pentameric ligand-gated ion channels (pLGICs) display. Here we present a comprehensive analysis of more than 30 cys-loop receptor structures of homologous proteins that revea...

The present work was performed to show the possible interaction of GAB A, and GABAB receptors in catalepsy. The following results were obtained: 1- Muscimol (MUS), a GABAA agonist, induced catalepsy. This effect was dose-dependent. Baclofen (BAC), a GABAB agonist, had no effect in this respect. 2- Catalepsy induced by muscimol was potentiated by pretreatment of animals with bicuculline (BI...

GABAA receptor α5 subunits, which are heavily expressed in the hippocampus, are potential drug targets for improving cognitive function. They are found at synaptic and extrasynaptic sites and have been shown to mediate tonic inhibition in pyramidal neurons. We tested the hypothesis that α5 subunits also contribute to synaptic inhibition by measuring the effect of diazepam (DZ) on spontaneous an...

Pregnancy needs complex pathways that together play a role in proper growth and protection of the fetus preventing its premature loss. Changes during pregnancy and postpartum period include the manifold machinery of neuroactive steroids that plays a crucial role in neuronal excitability by local modulation of specific inhibitory receptors: the GABAA receptors. Marked fluctuations in both blood ...