ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Midazolam inhibits hippocampal long-term potentiation and learning through dual central and peripheral benzodiazepine receptor activation and neurosteroidogenesis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 98 citations in OpenAlex.
- Distinct Modulation of High- and Low-Frequency Activity by Midazolam and Neurosteroids in Neocortical Slices.International journal of molecular sciences · 2026Article
- Synaptic correlates of benzodiazepine tolerance.Molecular psychiatry · 2026Review
- Benzodiazepines for anxiety and depression: an updated overview of current use and major outcomes.Molecular biology reports · 2026Review
- Effects of acute pro-inflammatory stimulation and 25-hydroxycholesterol on hippocampal plasticity and learning involve NLRP3 inflammasome and cellular stress responses.Scientific reports · 2025Article
- Sertraline modulates hippocampal plasticity via sigma 1 receptors, cellular stress and neurosteroids.Translational psychiatry · 2024Article
- Article
- Association of Neonatal Midazolam Exposure With Hippocampal Growth and Working Memory Performance in Children Born Preterm.Neurology · 2023Article
- The herbicide glyphosate inhibits hippocampal long-term potentiation and learning through activation of pro-inflammatory signaling.Scientific reports · 2023Article
- Neurosteroid influence on affective tone.Neuroscience and biobehavioral reviews · 2023Review
- Neurosteroid enantiomers as potentially novel neurotherapeutics.Neuroscience and biobehavioral reviews · 2023Review
- Neurosteroids as stress modulators and neurotherapeutics: lessons from the retina.Neural regeneration research · 2023Review
- Article
- SSRIs differentially modulate the effects of pro-inflammatory stimulation on hippocampal plasticity and memory via sigma 1 receptors and neurosteroids.Translational psychiatry · 2023Article
- Nitrous Oxide, a Rapid Antidepressant, Has Ketamine-like Effects on Excitatory Transmission in the Adult Hippocampus.Biological psychiatry · 2022Article
- Acrylamide inhibits long-term potentiation and learning involving microglia and pro-inflammatory signaling.Scientific reports · 2022Article
- Midazolam Exposure Impedes Oligodendrocyte Development via the Translocator Protein and Impairs Myelination in Larval Zebrafish.Molecular neurobiology · 2022Article
- A Proinflammatory Stimulus Disrupts Hippocampal Plasticity and Learning via Microglial Activation and 25-Hydroxycholesterol.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Oxysterols Modulate the Acute Effects of Ethanol on HippocampalThe Journal of pharmacology and experimental therapeutics · 2021Article
- Inhibitors of cellular stress overcome acute effects of ethanol on hippocampal plasticity and learning.Neurobiology of disease · 2020Article
- Voltage dependent allosteric modulation of IPSCs by benzodiazepines.Brain research · 2020Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Benzodiazepines (BDZs) enhance GABA(A) receptor inhibition by direct actions on central BDZ receptors (CBRs). Although some BDZs also bind mitochondrial receptors [translocator protein (18 kDa) (TSPO)] and promote the synthesis of GABA-enhancing neurosteroids, the role of neurosteroids in the clinical effects of BDZs is unknown. In rat hippocampal slices, we compared midazolam, an anesthetic BDZ, with clonazepam, an anticonvulsant/anxiolytic BDZ that activates CBRs selectively. Midazolam, but not clonazepam, increased neurosteroid levels in CA1 pyramidal neurons without changing TSPO immunostaining. Midazolam, but not clonazepam, also augmented a form of spike inhibition after stimulation adjacent to the pyramidal cell layer and inhibited induction of long-term potentiation. These effects were prevented by finasteride, an inhibitor of neurosteroid synthesis, or 17PA [17-phenyl-(3α,5α)-androst-16-en-3-ol], a blocker of neurosteroid effects on GABA(A) receptors. Moreover, the synaptic effects were mimicked by a combination of clonazepam with FGIN (2-[2-(4-fluorophenyl)-1H-indol-3-yl]-N,N-dihexylacetamide), a selective TSPO agonist, or a combination of clonazepam with exogenous allopregnanolone. Consistent with these in vitro results, finasteride abolished the effects of midazolam on contextual fear learning when administrated 1 d before midazolam injection. Thus, dual activation of CBRs and TSPO appears to result in unique actions of clinically important BDZs. Furthermore, endogenous neurosteroids are shown to be important regulators of pyramidal neuron function and synaptic plasticity.
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Registered trials
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.