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CC BY-NC-ND 4.0 · Arq Neuropsiquiatr 2021; 79(03): 216-221
DOI: 10.1590/0004-282X-ANP-2019-0393
ARTICLE

Phytohormone abscisic acid boosts pentobarbital-induced sleep through activation of GABA-A, PPARβ and PPARγ receptor signaling

O fito-hormônio ácido abscísico estimula o sono induzido por fenobarbital por meio de ativação da sinalização de receptores GABA-A, PPARβ e PPARγ
Mohammad MADADZADEH 
1   Shahid Bahonar University of Kerman, Faculty of Sciences, Department of Biology, Kerman, Iran.
,
Mehdi ABBASNEJAD 
1   Shahid Bahonar University of Kerman, Faculty of Sciences, Department of Biology, Kerman, Iran.
,
Mahtab MOLLASHAHI 
1   Shahid Bahonar University of Kerman, Faculty of Sciences, Department of Biology, Kerman, Iran.
,
Ali Mohammad POURRAHIMI 
2   Kerman University of Medical Sciences, Institute of Neuropharmacology, Kerman Neuroscience Research Center, Kerman, Iran.
,
Saeed ESMAEILI-MAHANI 
1   Shahid Bahonar University of Kerman, Faculty of Sciences, Department of Biology, Kerman, Iran.
› InstitutsangabenGefördert durch: Shahid Bahonar University of Kerman 9711
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ABSTRACT

Background: Sleep disorders induce anxiety and forgetfulness and change habits. The chemical hypnotic drugs currently used have serious side effects and, therefore, people are drawn towards using natural compounds such as plant-based healing agents. Abscisic acid (ABA) is produced in a variety of mammalian tissues and it is involved in many neurophysiological functions. Objective: To investigate the possible effect of ABA on pentobarbital-induced sleep and its possible signaling through GABA-A and PPAR (γ and β) receptors, in male Wistar rats. Methods: The possible effect of ABA (5 and 10 μg/rat, intracerebroventricularly) on sleep onset latency time and duration was evaluated in a V-maze model of sleep. Pentobarbital sodium (40 mg/kg, intraperitoneally) was injected to induce sleep 30 min after administration of ABA. PPARβ (GSK0660, 80 nM/rat), PPARγ (GW9662, 3 nM/rat) or GABA-A receptor (bicuculline, 6 μg/rat) antagonists were given 15 min before ABA injection. Diazepam (2 mg/kg, intraperitoneally) was used as a positive control group. Results: ABA at 5 μg significantly boosted the pentobarbital-induced subhypnotic effects and promoted induction of sleep onset in a manner comparable to diazepam treatment. Furthermore, pretreatment with bicuculline significantly abolished the ABA effects on sleep parameters, while the amplifying effects of ABA on the induction of sleep onset was not significantly affected by PPARβ or PPARγ antagonists. The sleep prolonging effect of ABA was significantly prevented by both PPAR antagonists. Conclusions: The data showed that ABA boosts pentobarbital-induced sleep and that GABA-A, PPARβ and PPARγ receptors are, at least in part, involved in ABA signaling.

RESUMO

Introdução: Os distúrbios do sono induzem a ansiedade e esquecimento e mudam hábitos. Os medicamentos hipnóticos químicos utilizados atualmente têm efeitos colaterais graves e, portanto, as pessoas são atraídas para o uso de compostos naturais, como agentes de cura à base de plantas. O ácido abscísico (ABA) é produzido em uma variedade de tecidos de mamíferos e está envolvido em muitas funções neurofisiológicas. Objetivo: Investigar o possível efeito do ABA no sono induzido por pentobarbital e sua possível sinalização por meio dos receptores GABA-A e PPAR (γ e β), em ratos Wistar machos. Métodos: O possível efeito do ABA (5 e 10 μg/rato, intracerebroventricularmente) no tempo de latência e duração do início do sono foi avaliado em um modelo de labirinto em V de sono. Pentobarbital sódico (40 mg/kg, intraperitonealmente) foi injetado para induzir o sono 30 minutos após a administração de ABA. PPARβ (GSK0660, 80 nM/rato), PPARγ (GW9662, 3 nM/rato) ou antagonistas do receptor GABA-A (bicuculina, 6 μg/rato) foram administrados 15 minutos antes da injeção de ABA. Diazepam (2 mg/kg, intraperitonealmente) foi utilizado como grupo de controle positivo. Resultados: ABA a 5 μg aumentou significativamente os efeitos sub-hipnóticos induzidos por pentobarbital e promoveu a indução do início do sono de forma comparável ao tratamento com diazepam. Além disso, o pré-tratamento com bicuculina aboliu significativamente os efeitos do ABA nos parâmetros do sono, ao passo que os efeitos amplificadores do ABA na indução do início do sono não foram significativamente afetados pelos antagonistas do PPARβ ou PPARγ. O efeito de prolongamento do sono do ABA foi significativamente prevenido por ambos os antagonistas do PPAR. Conclusões: Os dados mostraram que o ABA estimula o sono induzido por pentobarbital e que os receptores GABA-A, PPARβ e PPARγ estão, pelo menos em parte, envolvidos na sinalização ABA.

Keywords:

Abscisic Acid - Sleep - Pentobarbital - PPAR beta - Receptors, GABA-A - Rats

Palavras-chave:

Ácido Abscísico - Sono - Pentobarbital - PPAR-beta - Receptores de GABA-A - Ratos

Authors’ contributions:

MA: supervised the study and edited the manuscript. MM: preformed the experiments. MM: analyzed the data and drafted the manuscript. AMP and SEM: co-wrote the manuscript.




Publikationsverlauf

Eingereicht: 29. Oktober 2019

Angenommen: 22. Juli 2020

Artikel online veröffentlicht:
07. Juni 2023

© 2021. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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