ArticleThe European journal of neuroscience2009
Inhibition of thalamic excitability by 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-ol: a selective role for delta-GABA(A) receptors.
Article in The European journal of neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 67 citations in OpenAlex.
- An open-label, proof-of-mechanism trial evaluating a neuroactive steroid GABA modulator in tinnitus.Frontiers in neurology · 2025Trial
- Ethanol-induced rapid eye movement sleep suppression in rats: Comparison with subtype-selective GABAJournal of psychopharmacology (Oxford, England) · 2025Article
- Mechanisms of GABAergic and cholinergic neurotransmission in auditory thalamus: Impact of aging.Hearing research · 2021Review
- A multiorganism pipeline for antiseizure drug discovery: Identification of chlorothymol as a novel γ-aminobutyric acidergic anticonvulsant.Epilepsia · 2020Article
- Realising the therapeutic potential of neuroactive steroid modulators of the GABANeurobiology of stress · 2020Article
- Neuroendocrine aspects of improving sleep in epilepsy.Epilepsy research · 2018Review
- Suppression of Harmaline Tremor by Activation of an Extrasynaptic GABATremor and other hyperkinetic movements (New York, N.Y.) · 2018Article
- Neurosteroid biosynthesis down-regulation and changes in GABABritish journal of pharmacology · 2017Review
- Anticonvulsive evaluation of THIP in the murine pentylenetetrazole kindling model: lack of anticonvulsive effect of THIP despite functional δ-subunit-containing GABAPharmacology research & perspectives · 2017Article
- Reduced GABAergic transmission in the ventrobasal thalamus contributes to thermal hyperalgesia in chronic inflammatory pain.Scientific reports · 2017Article
- Reduced tonic inhibition after stroke promotes motor performance and epileptic seizures.Scientific reports · 2016Article
- Effects of gaboxadol on the expression of cocaine sensitization in rats.Experimental and clinical psychopharmacology · 2016Article
- Sex Differences in GABAA Signaling in the Periaqueductal Gray Induced by Persistent Inflammation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Assessment of subunit-dependent direct gating and allosteric modulatory effects of carisoprodol at GABA(A) receptors.Neuropharmacology · 2015Article
- Developmentally regulated neurosteroid synthesis enhances GABAergic neurotransmission in mouse thalamocortical neurones.The Journal of physiology · 2015Article
- Probing α4βδ GABAA receptor heterogeneity: differential regional effects of a functionally selective α4β1δ/α4β3δ receptor agonist on tonic and phasic inhibition in rat brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- The general anaesthetic etomidate inhibits the excitability of mouse thalamocortical relay neurons by modulating multiple modes of GABAA receptor-mediated inhibition.The European journal of neuroscience · 2014Article
- Menthol enhances phasic and tonic GABAA receptor-mediated currents in midbrain periaqueductal grey neurons.British journal of pharmacology · 2014Article
- Altered localization of the δ subunit of the GABAA receptor in the thalamus of α4 subunit knockout mice.Neurochemical research · 2014Article
- Tonic inhibition of accumbal spiny neurons by extrasynaptic α4βδ GABAA receptors modulates the actions of psychostimulants.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
The sedative and hypnotic agent 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-ol (THIP) is a GABA(A) receptor (GABA(A)R) agonist that preferentially activates delta-subunit-containing GABA(A)Rs (delta-GABA(A)Rs). To clarify the role of delta-GABA(A)Rs in mediating the sedative actions of THIP, we utilized mice lacking the alpha(1)- or delta-subunit in a combined electrophysiological and behavioural analysis. Whole-cell patch-clamp recordings were obtained from ventrobasal thalamic nucleus (VB) neurones at a holding potential of -60 mV. Application of bicuculline to wild-type (WT) VB neurones revealed a GABA(A)R-mediated tonic current of 92 +/- 19 pA, which was greatly reduced (13 +/- 5 pA) for VB neurones of delta(0/0) mice. Deletion of the delta- but not the alpha(1)-subunit dramatically reduced the THIP (1 mum)-induced inward current in these neurones (WT, -309 +/- 23 pA; delta(0/0), -18 +/- 3 pA; alpha(1) (0/0), -377 +/- 45 pA). Furthermore, THIP selectively decreased the excitability of WT and alpha(1) (0/0) but not delta(0/0) VB neurones. THIP did not affect the properties of miniature inhibitory post-synaptic currents in any of the genotypes. No differences in rotarod performance and locomotor activity were observed across the three genotypes. In WT mice, performance of these behaviours was impaired by THIP in a dose-dependent manner. The effect of THIP on rotarod performance was blunted for delta(0/0) but not alpha(1) (0/0) mice. We previously reported that deletion of the alpha(1)-subunit abolished synaptic GABA(A) responses of VB neurones. Therefore, collectively, these findings suggest that extrasynaptic delta-GABA(A)Rs vs. synaptic alpha(1)-subunit-containing GABA(A)Rs of thalamocortical neurones represent an important molecular target underpinning the sedative actions of THIP.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.