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Effect of Withania somnifera (L.) Dunal aqueous root extract on reinstatement using conditioned place preference and brain GABA and dopamine levels in alcohol dependent animals

Marathe, PA, Satam, SD, Raut, SB, Shetty, YC, Pooja, SG, Raut, AA, Kale, PP and Rege, NN 2021 , 'Effect of Withania somnifera (L.) Dunal aqueous root extract on reinstatement using conditioned place preference and brain GABA and dopamine levels in alcohol dependent animals' , Journal of Ethnopharmacology, vol. 274 , pp. 1-6 , doi: 10.1016/j.jep.2020.113304.

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Abstract

Ethnopharmacological relevance: Withania somnifera (L.) Dunal (WS), a known'Rasayana' (rejuvenating agent) as per Ayurveda is prescribed to promote health, to increase longevity and to hasten recovery in disease convalescent stages. WS has demonstrated protective effect on alcohol dependence and withdrawal anxiety in previous experimental studies.Aim of the study: To evaluate effect of WS on conditioned place behavioral paradigm (model of relapse) and on GABA and dopamine levels in critical brain areas in alcohol dependent animals.Methodology: Following Animal Ethics Committee permission, the mice (n = 24) were divided into the following study groups for experiment 1: 1 -distilled water (vehicle control), 2 -WS and 3 -Naltrexone. They were conditioned on conditioned place preference (CPP) using alcohol (2 gm/kg)/saline (1 ml) administered intraperitoneally for 8 days. WS and Naltrexone were administered during the period of extinction (6-8 days). Effect of WS (650 mg/kg) on reinstating behaviour of mice (time spent in alcohol paired compartment) primed with alcohol injection was noted. In experiment 2, effect of WS (450 mg/kg/) on GABA and dopamine levels in the midbrain, striatum and cortex (ng/gm) were measured in alcohol dependent rats (n = 24) following the first phase of standardisation assay (n = 36). The rats were made alcohol dependent for 15 days (intermittent access model) and WS was administered concurrently. GABA and dopamine levels were measured on Day 16.Results: WS group showed decrease in time spent in alcohol paired compartment alike Naltrexone and it differed significantly compared to the distilled water control group (p Conclusion: somnifera protected animals from relapse and showed beneficial effects on the brain neurotransmitters involved in alcohol dependence. The study provides substantial evidence for its potential application in alcohol use disorder.

Item Type: Article
Authors/Creators:Marathe, PA and Satam, SD and Raut, SB and Shetty, YC and Pooja, SG and Raut, AA and Kale, PP and Rege, NN
Keywords: alcohol use disorder, Ayurveda, GABA, reinstatement, reward pathway, Withania somnifera (L.) Dunal
Journal or Publication Title: Journal of Ethnopharmacology
Publisher: Elsevier Sequoia
ISSN: 0378-8741
DOI / ID Number: 10.1016/j.jep.2020.113304
Copyright Information:

Copyright 2020 Elsevier B.V. All rights reserved.

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