Gammahydroxybutyrate (GHB) receptor ligand effects on evoked synaptic field potentials in CA1 of the rat hippocampal slice

King, Michael A.; Thinschmidt, J. S.; Walker, David A.

doi:10.1007/bf01294719

Cited by 12 publications

(10 citation statements)

References 67 publications

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“…Live, acute hippocampal slices were prepared by procedures used routinely to produce slices that can remain electrophysiologically active for up to 12 hr after preparation (King et al, 1997; Thinschmidt et al, 2003). Rats were euthanized by rapid decapitation under general anesthesia induced with an intraperitoneal injection (0.875 ml/kg of 5:9 mixture of 20 mg/ml xylazine:100 mg/ml ketamine).…”

Section: Methodsmentioning

confidence: 99%

Endothelin‐1 modulates anterograde fast axonal transport in the central nervous system

Stokely

Yorio

King

2005

J of Neuroscience Research

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Anterograde fast axonal transport (FAxT) maintains synaptic function and provides materials necessary for neuronal survival. Localized changes in FAxT are associated with a variety of central nervous system (CNS) neuropathies, where they may contribute to inappropriate remodeling, a process more appropriately involved in synaptic plasticity and development. In some cases, developmental remodeling is regulated by localized secretion of endothelins (ETs), neuroinflammatory peptides that are also pathologically elevated in cases of neurologic disease, CNS injury, or ischemia. To investigate the potential role of ETs in these processes, we decided to test whether locally elevated endothelin-1 (ET-1) modulates FAxT in adult CNS tissues. We used the established in vivo rat optic nerve model and a novel ex vivo rat hippocampal slice model to test this hypothesis. In vivo, exogenously elevated vitreal ET-1 significantly affected protein composition of FAxT-cargos as well as the abundance and peak delivery times for metabolically-labeled proteins that were transported into the optic nerve. Proteins with molecular weights of 139, 118, 89, 80, 64, 59, 51, 45, 42, 37, and 25 kDa were evaluated at injection-sacrifice intervals (ISIs) of 24, 28, 32, and 36 hr. In acute hippocampal slices maintained on nonvascular supplies of glucose and oxygen, ET-1 significantly decreased the distance traveled along the Schaffer collateral tract by nonmetabolically-labeled lipid rafts at 5 and 10 min after pulse-labeling. In both models, ET-1 significantly affected transport or targeted delivery of FaxT-cargos, suggesting that ET-1 has the potential to modulate FAxT in adult CNS tissues.

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Section: Methodsmentioning

confidence: 99%

Endothelin‐1 modulates anterograde fast axonal transport in the central nervous system

Stokely

Yorio

King

2005

J of Neuroscience Research

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“…Moreover, King et al (46) revealed that GHB dose-dependently depresses the field potential (FP) in vitro. This action of GHB was depressed by a large concentration of 2-OH-saclofen, but not by NCS-382 at concentrations up to 5 mM.…”

Section: In Vivo and In Vitro Effects Of Ncs-382mentioning

confidence: 98%

“…Accordingly, Xie and Smart (74) showed a hyperpolarization and a small membrane conductance increase when GHB was applied to hippocampal CA1 pyramidal neurons; this effect being completely abolished by the GABA B antagonist, CGP 35348. Moreover, King et al (46) revealed that GHB dose-dependently depresses the field potential (FP) in vitro. This action of GHB was depressed by a large concentration of 2-OH-saclofen, but not by NCS-382 at concentrations up to 5 mM.…”

Section: In Vivo and In Vitro Effects Of Ncs-382mentioning

confidence: 99%

A Review of Pharmacology of NCS‐382, a Putative Antagonist of γ‐Hydroxybutyric Acid (GHB) Receptor

et al. 2004

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Gamma-hydroxybutyric acid (GHB), a naturally occurring metabolite of gamma-aminobutyric acid (GABA), has been postulated to act as a specific agonist of GHB receptors and as well as a weak GABA(B) receptor agonist. To date, 6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylideneacetic acid (NCS-382), a semirigid compound structurally related to GHB, is the only compound reported to be an antagonist of the GHB receptor sites. In this article we review the in vivo and in vitro pharmacological properties of NCS-382 and its interaction with GHB and GABA(B) receptors. Binding studies have demonstrated that NCS-382 is a stereoselective ligand for GHB-binding sites, with both, the high and the low component of population, showing the same distribution of GHB receptors. Indeed, this compound did not display affinity for GABA(A), GABA(B), or any other known receptors, while conflicting data have been reported as to its selective antagonist action at GHB receptor. Only a few studies have shown that NCS-382 antagonizes GHB-induced effect, but a re-evaluation of all data reported in the literature suggests that the antagonistic effect of this compound could be due to an indirect action at GABA(B) receptors. As revealed by several behavioral studies, NCS-382 fails to antagonize GHB discriminative stimuli, GHB-induced inhibition of locomotor activity and ataxia or suppression of operant responses. Moreover, it is capable of either eliciting qualitatively similar effects to those of GHB or enhancing some actions of GHB. In addition, the NCS-382-sensitive electrophysiological effects of endogenous and exogenous GHB observed in vivo have not been completely replicated in vitro. The only electrophysiological action of GHB antagonized in vitro by NCS-382 required a previous blockade of GABA(B) receptors. We concluded that NCS-382 is a good ligand but not a selective antagonist for GHB receptor.

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“…This depression was obtained at higher concentrations (10 mM) than those of the present study and it was reversibly blocked by a selective GABA B antagonist. Thus, GHB can also activate presynaptic GABA B receptors to reduce inhibitory and excitatory transmitter release as described in other reports (Xie and Smart, 1992a, b;King et al, 1997). In the presence of TTX (1 mM), no reduction in mIPSCs amplitude and frequency was observed indicating that the depressing effect of GHB on sIPSCs was not due to a reduced postsynaptic sensitivity to GABA but to a presynaptic depression of GABA release.…”

Section: Discussionmentioning

confidence: 71%

“…Spontaneous synaptic currents were recorded from SNc dopaminergic neurons in the presence of the GABA B antagonist CGP 55845A (1 mM) to prevent the effects of GHB on the GABA B receptor (Xie and Smart, 1992a, b;King et al, 1997). This spontaneous activity appeared as rapidly rising inward currents at a frequency of 8.91 7 0.75 Hz and an amplitude of 28.1 7 2.4 pA (n ¼ 8).…”

Section: Effects Of Ghb On Sipscsmentioning

confidence: 99%

Presynaptic Modulation of Spontaneous Inhibitory Postsynaptic Currents by Gamma-hydroxybutyrate in the Substantia Nigra Pars Compacta

Brancucci

Berretta

Mercuri

et al. 2003

Neuropsychopharmacol

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The regulation of GABA release from the inhibitory input to dopamine cells in the substantia nigra pars compacta (SNc) plays a key role in different reward-related behaviors. Gamma-hydroxybutyrate (GHB) has therapeutical properties in various psychiatric disorders, especially in alcohol abuse. GHB is also used as a drug of abuse, which induces sedation and euphoria. Using whole-cell patch-clamp recordings, we studied the effects of GHB on GABA release in the SNc by recording spontaneous inhibitory postsynaptic currents (sIPSCs) in brain slices of 21-to 25-day-old rats. We found that GHB depressed the frequency and amplitude of sIPSCs, while the frequency and the amplitude of miniature inhibitory postsynaptic currents (mIPSCs), recorded in the presence of TTX, were not affected. However, in the presence of high extracellular potassium (15 mM), which increases the contribution of voltage-dependent calcium channels, GHB induced a reduction in the frequency of the mIPSCs without any effect on their amplitude. All of these effects were GABA B -independent and they were blocked by the GHB receptor antagonist NCS-382. The present results indicate that GHB inhibits spontaneous inhibitory synaptic transmission recorded from dopaminergic neurons in the SNc likely by reducing voltage-dependent calcium influx involved in presynaptic GABA release.

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Gammahydroxybutyrate (GHB) receptor ligand effects on evoked synaptic field potentials in CA1 of the rat hippocampal slice

Cited by 12 publications

References 67 publications

Endothelin‐1 modulates anterograde fast axonal transport in the central nervous system

Endothelin‐1 modulates anterograde fast axonal transport in the central nervous system

A Review of Pharmacology of NCS‐382, a Putative Antagonist of γ‐Hydroxybutyric Acid (GHB) Receptor

Presynaptic Modulation of Spontaneous Inhibitory Postsynaptic Currents by Gamma-hydroxybutyrate in the Substantia Nigra Pars Compacta

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