Different roles of T-type calcium channel isoforms in hypnosis induced by an endogenous neurosteroid epipregnanolone.
Adjuvants, Anesthesia
/ pharmacology
Anesthetics, Inhalation
/ pharmacology
Animals
Behavior, Animal
/ drug effects
Calcium Channels, T-Type
/ drug effects
Electroencephalography
/ drug effects
Hypnotics and Sedatives
/ pharmacology
Isoflurane
/ pharmacology
Isomerism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Pregnanolone
/ pharmacology
Sevoflurane
/ pharmacology
Calcium
Isoflurane
Low-voltage-activated
Righting reflex
Thalamus
Withdrawal reflex
Journal
Neuropharmacology
ISSN: 1873-7064
Titre abrégé: Neuropharmacology
Pays: England
ID NLM: 0236217
Informations de publication
Date de publication:
01 10 2021
01 10 2021
Historique:
received:
19
03
2021
revised:
09
07
2021
accepted:
29
07
2021
pubmed:
3
8
2021
medline:
8
2
2022
entrez:
2
8
2021
Statut:
ppublish
Résumé
Many neuroactive steroids induce sedation/hypnosis by potentiating γ-aminobutyric acid (GABA Here, we utilized electroencephalographic (EEG) recordings to characterize thalamocortical oscillations, as well as behavioral assessment and mouse genetics with wild-type (WT) and different knockout (KO) models of T-channel isoforms to investigate potential sedative/hypnotic and immobilizing properties of EpiP. Consistent with increased oscillations in slower EEG frequencies, EpiP induced an hypnotic state in WT mice when injected alone intra-peritoneally (i.p.) and effectively facilitated anesthetic effects of isoflurane (ISO) and sevoflurane (SEVO). The Ca We posit that EpiP may have an important role as novel hypnotic and/or adjuvant to volatile anesthetic agents. We speculate that distinct hypnotic effects of EpiP across all three T-channel isoforms is due to their differential expression in thalamocortical circuitry.
Sections du résumé
BACKGROUND
Many neuroactive steroids induce sedation/hypnosis by potentiating γ-aminobutyric acid (GABA
METHODS
Here, we utilized electroencephalographic (EEG) recordings to characterize thalamocortical oscillations, as well as behavioral assessment and mouse genetics with wild-type (WT) and different knockout (KO) models of T-channel isoforms to investigate potential sedative/hypnotic and immobilizing properties of EpiP.
RESULTS
Consistent with increased oscillations in slower EEG frequencies, EpiP induced an hypnotic state in WT mice when injected alone intra-peritoneally (i.p.) and effectively facilitated anesthetic effects of isoflurane (ISO) and sevoflurane (SEVO). The Ca
CONCLUSION
We posit that EpiP may have an important role as novel hypnotic and/or adjuvant to volatile anesthetic agents. We speculate that distinct hypnotic effects of EpiP across all three T-channel isoforms is due to their differential expression in thalamocortical circuitry.
Identifiants
pubmed: 34339750
pii: S0028-3908(21)00294-X
doi: 10.1016/j.neuropharm.2021.108739
pmc: PMC8478885
mid: NIHMS1731270
pii:
doi:
Substances chimiques
Adjuvants, Anesthesia
0
Anesthetics, Inhalation
0
Cacna1g protein, mouse
0
Cacna1i protein, mouse
0
Calcium Channels, T-Type
0
Hypnotics and Sedatives
0
Sevoflurane
38LVP0K73A
Pregnanolone
BXO86P3XXW
Isoflurane
CYS9AKD70P
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108739Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM102525
Pays : United States
Organisme : NINDS NIH HHS
ID : P30 NS048154
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM123746
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH115045
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM141802
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
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