Agomelatine attenuates alcohol craving and withdrawal symptoms by modulating the Notch1 signaling pathway in rats.
Life Sci
; 284: 119904, 2021 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-34453945
ABSTRACT
AIM:
Alcohol abuse is a significant causative factor of death worldwide. The Notch1 signaling pathway is involved in alcohol tolerance, withdrawal and dependence. Agomelatine is a known antidepressant acting as a melatonin receptor (MT1/2) agonist and a 5-hydroxytryptamine receptor-2C antagonist. However, its effects on alcohol cravings and alcohol withdrawal symptoms have not been investigated. In this study, we assessed the possibility of using agomelatine for the treatment of these symptoms in a rat model of alcoholism and the possible role of Notch1 signaling. MAINMETHODS:
We induced alcoholism in rats using a free-choice drinking model for 60 days. From day 61, free-choice was continued until day 82 for the craving model, whereas only water was offered in the withdrawal model. Meanwhile, the treated groups for both models received agomelatine (50 mg/kg/day) orally from day 61 to 82, followed by behavioral, histopathological and biochemical assessment. KEYFINDINGS:
Agomelatine treatment caused significant decrease in alcohol consumption with a positive effect on anxiety-like behavior in the open field, memory in the Morris water maze and immobility in the forced swim test. Moreover, agomelatine induced the expression of Notch1 pathway markers, including Notch1, NICD, CREB, CCNE-2, Hes-1, both total and phosphorylated ERK1/2, MMP9, Per2and RGS-2 in the hippocampal formation. By contrast, NMDAR expression was reduced. Furthermore, agomelatine normalized the serum levels of BDNF, cortisol, dopamine and glutamate which were disrupted by alcohol consumption.SIGNIFICANCE:
Based on these findings, agomelatine reversed alcohol cravings and withdrawal symptoms associated with alcohol dependence by modulating the Notch1 signaling pathway.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Abstinência a Substâncias
/
Transdução de Sinais
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Bebidas Alcoólicas
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Receptor Notch1
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Fissura
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Acetamidas
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Life Sci
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Egito