Abstract:
:Evidences have indicated a high degree of comorbidity of alcoholism and depression. N-acetylcysteine (NAC) has shown its clinical efficiency in the treatment of several psychiatric disorders and is identified as a multi-target acting drug. The ability of NAC to prevent alcohol abstinence-induced depression-like effects and underlying mechanism(s) have not been adequately addressed. This study was aimed to investigate the beneficial effects of NAC in the alcohol abstinence-induced depression developed following long-term voluntary alcohol intake. For evaluation of the effects of NAC, Sprague-Dawley rats were enabled to voluntary drinking of 4.5%, 7.5% and 9% v/v alcohol for fifteen days. NAC (25, 50, and 100 mg/kg) and fluoxetine (5 mg/kg) were injected intraperitoneally for three consecutive days during the alcohol abstinence period on the days 16, 17, 18. The behavioral studies were conducted employing forced swim test (FST), and tail suspension test (TST) on day 18 to determine the effects of N-acetylcysteine and fluoxetine in the ethanol withdrawal induced-depression. Blood alcohol concentration, alcohol biomarkers like SGPT, SGOT, ALP, GGT, and MCV were estimated by using commercially available kits. Serotonin concentrations were measured in the plasma, hippocampus and pre-frontal cortex using the rat ELISA kit. The expression of GRIN1, GRIN2A, GRIN2B genes for the N-methyl d-aspartate receptors (NMDAR) subunits in the hippocampus and the prefrontal cortex were also examined by reverse-transcription quantitative polymerase chain reaction. The results revealed that alcohol abstinence group depicted increased immobility time in FST and TST. Further, NAC exerted significant protective effect at the doses 50 mg/kg and 100 mg/kg, but 25 mg/kg showed insignificant protection against alcohol abstinence-induced depression. The increased level of biochemical parameters following ethanol abstinence were also reversed by NAC at the dose of 100 mg/kg. The significant reversal effect of NAC on the serotonin level following alcohol abstinence was greater in the hippocampus as compared to the third-day alcohol withdrawal group. The increased expression levels of GRIN2A and GRIN2B following ethanol abstinence were reversed with a higher dose of NAC (100 mg/kg) treatment. In conclusion, the results of the study reveal that NAC has remarkable protective effects in the alcohol abstinence-induced depression by modulating alcohol markers, serotonin levels and GRIN2A, GRIN2B gene expression of NMDAR signaling pathway in rats.
journal_name
Neurochem Intjournal_title
Neurochemistry internationalauthors
Yawalkar R,Changotra H,Gupta GLdoi
10.1016/j.neuint.2018.04.011subject
Has Abstractpub_date
2018-09-01 00:00:00pages
73-81eissn
0197-0186issn
1872-9754pii
S0197-0186(18)30062-7journal_volume
118pub_type
杂志文章abstract::Stroke causes neuronal cell death and destruction of neuronal circuits in the brain and spinal cord. Injury to the brain tissue induces sterile inflammation triggered by the extracellular release of endogenous molecules, but cerebral inflammation after stroke is gradually resolved within several days. In this pro-reso...
journal_title:Neurochemistry international
pub_type: 杂志文章,评审
doi:10.1016/j.neuint.2018.10.013
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journal_title:Neurochemistry international
pub_type: 杂志文章,评审
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journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2007.10.004
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journal_title:Neurochemistry international
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journal_title:Neurochemistry international
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