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Effect of Lipopolysaccharide on the Duration of Zolpidem-Induced Loss of Righting Reflex in Mice.
- Source :
-
Acta medica Okayama [Acta Med Okayama] 2024 Jun; Vol. 78 (3), pp. 227-235. - Publication Year :
- 2024
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Abstract
- Zolpidem, a non-benzodiazepine hypnotic, is primarily used to treat insomnia. In a previous study, pior treatment with non-benzodiazepine receptor agonists was associated with inflammation. The present study aimed to clarify the association between the effects of zolpidem and inflammation in mice treated with lipopolysaccharide (LPS), a known model of inflammation. We assessed the zolpidem-induced loss of righting reflex (LORR) duration 24 h after LPS treatment in mice. Additionally, the expressions of γ-aminobutyric acid (GABA)A receptor subunit and K+-Cl- cotransporter isoform 2 (KCC2) mRNA in the hippocampus and frontal cortex were examined in LPS-treated mice. Pretreatment with LPS was associated with significantly prolonged duration of zolpidem-induced LORR compared to control mice. This effect was significantly attenuated by administering bicuculline, a GABAA receptor antagonist, or flumazenil, a benzodiazepine receptor antagonist, in LPS-treated mice. Compared to controls, LPS-treated mice showed no significant change in the expression of GABAA receptor subunits in the hippocampus or frontal cortex. Bumetanide, an Na+-K+-2Cl- cotransporter isoform 1 blocker, attenuated the extended duration of zolpidem-induced LORR observed in LPS-treated mice. LPS significantly decreased Kcc2 mRNA expression in the hippocampus and the frontal cortex. These findings suggest that inflammation increases zolpidem-induced LORR, possibly through a reduction in KCC2 expression.<br />Competing Interests: No potential conflict of interest relevant to this article was reported.
- Subjects :
- Animals
Mice
Male
Hippocampus drug effects
Hippocampus metabolism
K Cl- Cotransporters
Hypnotics and Sedatives pharmacology
Inflammation chemically induced
Frontal Lobe drug effects
Frontal Lobe metabolism
Zolpidem pharmacology
Lipopolysaccharides
Pyridines pharmacology
Receptors, GABA-A metabolism
Receptors, GABA-A drug effects
Symporters genetics
Symporters metabolism
Reflex, Righting drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0386-300X
- Volume :
- 78
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Acta medica Okayama
- Publication Type :
- Academic Journal
- Accession number :
- 38902210
- Full Text :
- https://doi.org/10.18926/AMO/67197