Effects of pentobarbital on GABA-activated currents in acutely-isolated rat dentate gyrus granule neurons

Lim, M.; Lindquist, Catarina; Birnir, Bryndis

doi:10.1016/j.neulet.2003.09.025

Cited by 5 publications

(3 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Barbiturates, and particularly pentobarbital (PtB), greatly increase the duration of mIPSCs in neonatal hippocampal slices (40,41). The concentration of PtB that produces the maximal allosteric effect is difficult to determine because PtB also directly activates chloride channels in the adult brain (42–45). However, in rat hippocampal neurons, a value of 100 μ M is considered to maximally increase GABA A receptor–mediated response by an allosteric mechanism (42,46).…”

Section: Resultsmentioning

confidence: 99%

“…The concentration of PtB that produces the maximal allosteric effect is difficult to determine because PtB also directly activates chloride channels in the adult brain (42–45). However, in rat hippocampal neurons, a value of 100 μ M is considered to maximally increase GABA A receptor–mediated response by an allosteric mechanism (42,46). At this concentration, in immature pyramidal neurons, PtB (n = 10) considerably increased the decay‐time constant (335 ± 14%; p < 0.0001) but not the frequency of mIPSCs (p = 0.27; Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Stiripentol, a Putative Antiepileptic Drug, Enhances the Duration of Opening of GABA_A‐Receptor Channels

Quilichini¹,

Chiron²,

Ben-Ari³

et al. 2006

Epilepsia

142

105

View full text Add to dashboard Cite

Summary:Purpose: Stiripentol (STP) is currently an efficient drug for add-on therapy in infantile epilepsies because it improves the efficacy of antiepileptic drugs (AEDs) through its potent inhibition of liver cytochromes P450. In addition, STP directly reduces seizures in several animal models of epilepsy, suggesting that it might also have anticonvulsive effects of its own. However, its underlying mechanisms of action are unknown.Methods: We examined the interactions of STP with γ -aminobutyric acid (GABA) transmission by using patch-clamp methods in CA3 pyramidal neurons in the neonatal rat.Results: STP markedly increased miniature inhibitory postsynaptic current (mIPSC) decay-time constant in a concentrationdependent manner. The prolongation of mIPSC duration does not result from an interaction with GABA transporters because it persisted in the presence of GAT-1 inhibitors (SKF-89976A and NO-711). An interaction with benzodiazepine or neurosteroid binding sites also was excluded because STP-mediated increase of decay time was still observed when these sites were initially saturated (by clobazam, zolpidem, or pregnanolone) or blocked (by flumazenil or dehydroepiandrosterone sulfate), respectively. In contrast, saturating barbiturate sites with pentobarbital clearly occluded this effect of STP, suggesting that STP and barbiturates interact at the same locus. This was directly confirmed by using outside-out patches, because STP increased the duration and not the frequency of opening of GABA A channels.Conclusions: At clinically relevant concentrations, STP enhances central GABA transmission through a barbiturate-like effect, suggesting that STP should possess an antiepileptic effect by itself.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Stiripentol, a Putative Antiepileptic Drug, Enhances the Duration of Opening of GABA_A‐Receptor Channels

Quilichini¹,

Chiron²,

Ben-Ari³

et al. 2006

Epilepsia

142

105

View full text Add to dashboard Cite

show abstract

“…Barbiturates, including pentobarbital, act at a modulatory site on the GABA A ‐R to increase Cl ‐ channel open probability in response to endogenous GABA or, at higher concentrations (>1 mM), to open the GABA A ‐R channel directly. This generally suppresses neuronal activity (Lim et al, 2003). Tonic inhibition of the pontine inhibitory area may be at least partially mediated by GABA released by afferents from distant GABAergic neurons as well as from local interneurons.…”

Section: Discussionmentioning

confidence: 99%

Movement suppression during anesthesia: Neural projections from the mesopontine tegmentum to areas involved in motor control

Sukhotinsky

Hopkins

Lü

et al. 2005

J of Comparative Neurology

View full text Add to dashboard Cite

Microinjection of pentobarbital and GABA(A)-receptor agonists into a brainstem region we have called the mesopontine tegmental anesthesia area (MPTA; Devor and Zalkind [2001] Pain 94:101-112) induces a general anesthesia-like state. As in systemic general anesthesia, rats show loss of the righting reflex, atonia, nonresponsiveness to noxious stimuli, and apparent loss of consciousness. GABA(A) agonist anesthetics acting on the MPTA might suppress movement by engaging endogenous motor regulatory systems previously identified in research on decerebrate rigidity and REM sleep atonia. Anterograde and retrograde tracing revealed that the MPTA has multiple descending projections to pontine and medullary areas known to be associated with motor control and atonia. Prominent among these are the dorsal pontine reticular formation and components of the rostral ventromedial medulla (RVM). The MPTA also has direct projections to the intermediate gray matter and ventral horn of the spinal cord via the lateral and anterior funiculi. These projections show a rostrocaudal topography: neurons in the rostral MPTA project to the RVM, but only minimally to the spinal cord, while those in the caudal MPTA project to both targets. Finally, the MPTA has ascending projections to motor control areas including the substantia nigra, subthalamic nucleus, and the caudate-putamen. Projections are bilateral with an ipsilateral predominance. We propose that GABA(A) agonist anesthetics induce immobility at least in part by acting on these endogenous motor control pathways via the MPTA. Analysis of MPTA connectivity has the potential for furthering our understanding of the neural circuitry responsible for the various functional components of general anesthesia.

show abstract

Networks for the Modulation of Acute and Chronic Pain

Sukhotinsky

Devor

2014

Neuronal Networks in Brain Function, CNS Disorders, and Therapeutics

View full text Add to dashboard Cite

Effects of pentobarbital on GABA-activated currents in acutely-isolated rat dentate gyrus granule neurons

Cited by 5 publications

References 13 publications

Stiripentol, a Putative Antiepileptic Drug, Enhances the Duration of Opening of GABA_A‐Receptor Channels

Stiripentol, a Putative Antiepileptic Drug, Enhances the Duration of Opening of GABA_A‐Receptor Channels

Movement suppression during anesthesia: Neural projections from the mesopontine tegmentum to areas involved in motor control

Networks for the Modulation of Acute and Chronic Pain

Contact Info

Product

Resources

About

Effects of pentobarbital on GABA-activated currents in acutely-isolated rat dentate gyrus granule neurons

Cited by 5 publications

References 13 publications

Stiripentol, a Putative Antiepileptic Drug, Enhances the Duration of Opening of GABAA‐Receptor Channels

Stiripentol, a Putative Antiepileptic Drug, Enhances the Duration of Opening of GABAA‐Receptor Channels

Movement suppression during anesthesia: Neural projections from the mesopontine tegmentum to areas involved in motor control

Networks for the Modulation of Acute and Chronic Pain

Contact Info

Product

Resources

About

Stiripentol, a Putative Antiepileptic Drug, Enhances the Duration of Opening of GABA_A‐Receptor Channels

Stiripentol, a Putative Antiepileptic Drug, Enhances the Duration of Opening of GABA_A‐Receptor Channels