دورية أكاديمية
أعرض في EDS

Combination administration of alprazolam and N-Ethylmaleimide synergistically enhances sleep behaviors in mice with no potential CNS side effects.

التفاصيل البيبلوغرافية
العنوان: Combination administration of alprazolam and N-Ethylmaleimide synergistically enhances sleep behaviors in mice with no potential CNS side effects.
المؤلفون: Zhu S; State Key Laboratory of NBC Protection for Civilian, Beijing, China., Shi J; State Key Laboratory of NBC Protection for Civilian, Beijing, China., Zhang Y; State Key Laboratory of NBC Protection for Civilian, Beijing, China., Chen X; State Key Laboratory of NBC Protection for Civilian, Beijing, China., Shi T; State Key Laboratory of NBC Protection for Civilian, Beijing, China., Li L; State Key Laboratory of NBC Protection for Civilian, Beijing, China.
المصدر: PeerJ [PeerJ] 2024 May 07; Vol. 12, pp. e17342. Date of Electronic Publication: 2024 May 07 (Print Publication: 2024).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: PeerJ Inc Country of Publication: United States NLM ID: 101603425 Publication Model: eCollection Cited Medium: Internet ISSN: 2167-8359 (Electronic) Linking ISSN: 21678359 NLM ISO Abbreviation: PeerJ Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Corte Madera, CA : PeerJ Inc.
مواضيع طبية MeSH: Alprazolam*/pharmacology , Alprazolam*/administration & dosage , Drug Synergism* , Sleep*/drug effects, Animals ; Mice ; Male ; Electroencephalography/drug effects ; Proto-Oncogene Proteins c-fos/metabolism ; Brain/drug effects ; Brain/metabolism ; Reflex, Righting/drug effects ; Hypnotics and Sedatives/pharmacology ; Hypnotics and Sedatives/administration & dosage
مستخلص: Background: N-Ethylmaleimide (NEM), an agonist of the potassium chloride cotransporters 2 (KCC2) receptor, has been correlated with neurosuppressive outcomes, including decreased pain perception and the prevention of epileptic seizures. Nevertheless, its relationship with sleep-inducing effects remains unreported.
Objective: The present study aimed to investigate the potential enhancement of NEM on the sleep-inducing properties of alprazolam (Alp).
Methods: The test of the righting reflex was used to identify the appropriate concentrations of Alp and NEM for inducing sleep-promoting effects in mice. Total sleep duration and sleep quality were evaluated through EEG/EMG analysis. The neural mechanism underlying the sleep-promoting effect was examined through c-fos immunoreactivity in the brain using immunofluorescence. Furthermore, potential CNS-side effects of the combination Alp and NEM were assessed using LABORAS automated home-cage behavioral phenotyping.
Results: Combination administration of Alp (1.84 mg/kg) and NEM (1.0 mg/kg) significantly decreased sleep latency and increased sleep duration in comparison to administering 1.84 mg/kg Alp alone. This effect was characterized by a notable increase in REM duration. The findings from c-fos immunoreactivity indicated that NEM significantly suppressed neuron activation in brain regions associated with wakefulness. Additionally, combination administration of Alp and NEM showed no effects on mouse neural behaviors during automated home cage monitoring.
Conclusions: This study is the first to propose and demonstrate a combination therapy involving Alp and NEM that not only enhances the hypnotic effect but also mitigates potential CNS side effects, suggesting its potential application in treating insomnia.
Competing Interests: The authors declare there are no competing interests.
(©2024 Zhu et al.)
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فهرسة مساهمة: Keywords: Alprazolam; Combination; Enhanced; KCC2; N-Ethylmaleimide; Side effect; Sleep behaviors
المشرفين على المادة: YU55MQ3IZY (Alprazolam)
0 (Proto-Oncogene Proteins c-fos)
0 (Hypnotics and Sedatives)
تواريخ الأحداث: Date Created: 20240513 Date Completed: 20240513 Latest Revision: 20240514
رمز التحديث: 20240514
مُعرف محوري في PubMed: PMC11086308
DOI: 10.7717/peerj.17342
PMID: 38737745
قاعدة البيانات: MEDLINE
الوصف
تدمد:2167-8359
DOI:10.7717/peerj.17342