Bacopa monnieri abrogates alcohol abstinence-induced anxiety-like behavior by regulating biochemical and Gabra1, Gabra4, Gabra5 gene expression of GABAA receptor signaling pathway in rats.


Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai, 400 056, India. Electronic address: [Email]


Evidence has revealed a high degree of comorbidity of excessive alcohol intake and abstinence anxiety-like behavior. The ethanolic extracts of Bacopa monnieri (BME) are used in Indian traditional medicines for the management of alcoholic disorders. However, the underlying mechanism(s) associated with the influence of BME on alcohol abstinence-induced anxiety-like behavior have not been adequately addressed. Therefore, the present study was planned to examine the beneficial effects of BME in alcohol abstinence-induced anxiety-like behavior and the underlying mechanism of action subsequent to long-term voluntary drinking of alcohol. For the assessment of the effects of BME, Wistar rats were exposed to voluntary ingestion of 4.5%, 7.5% and 9% v/v alcohol for 15 days. The doses (100, 200, and 500 mg/kg) of BME and diazepam (2 mg/kg) were administered via gavage for three consecutive days in the alcohol abstinence period on the days 16, 17, and 18. The behavioral studies were conducted employing the elevated plus maze test (EPM), and light-dark test on day 18 to determine the effects of BME and diazepam in the ethanol abstinence-induced anxiety-like behavior. Alcohol biomarkers like ALT, AST, ALP, GGT, and MCV were estimated using commercially available kits. The expression of Gabra1, Gabra2, Gabra3, Gabra4, Gabra5 genes of the GABAA receptors subunits in the hippocampus as well as amygdala were also examined by reverse-transcription quantitative polymerase chain reaction. The HPLC analysis demonstrated that BME contained 9.9% bacoside-A as a major component. The results revealed that alcohol abstinence group depicted a reduction in the time spent on the open arms, numbers of entries in the open as well as closed arms in EPM test and similarly decrease in latency to the dark chamber, time spent in light chamber and numbers of transitions in LDT. Further, BME at the doses of 200 mg/kg and 500 mg/kg alleviated anxiety-like behavior which was escalated during alcohol abstinence. However, BME (100 mg/kg) exhibited insignificant protection against alcohol abstinence-induced syndrome. The escalated levels of alcohol-intake biomarkers were also reversed by BME at the dose of 200 mg/kg and 500 mg/kg. The down-regulation of Gabra1, Gabra4, and Gabra5 gene expression following alcohol abstinence were also reversed with a higher dose of BME (200 and 500 mg/kg) treatment. These results show that BME abrogates anxiety-like behavior by modulating alcohol markers and Gabra1, Gabra4, Gabra5 gene expression of GABAA receptor signaling pathway in rats.


ALP,ALT,AST,Alcohol abstinence anxiety-like behavior,Alcohol markers,Bacopa monnieri,GGT,Gene expression,MCV,