Department of Pharmacology & Therapeutics, Seth Gordhandas Sundardas Medical College & King Edward Memorial Hospital, Parel, Mumbai, 400 012, India.
School of Psychological Sciences, College of Health and Medicine, University of Tasmania, Launceston, 7250, Australia.
J Ethnopharmacol. 2021 Jun 28;274:113304. doi: 10.1016/j.jep.2020.113304. Epub 2020 Sep 10.
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.
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.
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.
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 < 0.05) Alcohol-dependent rats showed significant decrease in GABA and increase in dopamine levels vs distilled water in the midbrain, striatum and cortex. WS and Naltrexone administration showed rise in GABA and fall in dopamine in all the isolated brain parts in the respective groups (p < 0.05 vs alcohol treated group).
Withania 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.
根据阿育吠陀医学，睡茄（Withania somnifera（L.）Dunal，WS）是一种已知的“Rasayana”（ rejuvenating agent），被用于促进健康、延长寿命和加速疾病康复阶段的恢复。WS 在以前的实验研究中显示出对酒精依赖和戒断焦虑的保护作用。
评估 WS 对条件性位置行为范式（复发模型）和酒精依赖动物关键脑区 GABA 和多巴胺水平的影响。
根据动物伦理委员会的许可，将小鼠（n=24）分为以下研究组进行实验 1：1-蒸馏水（载体对照）、2-WS 和 3-纳曲酮。它们通过腹腔内给予酒精（2gm/kg）/生理盐水（1ml）进行 8 天的条件性位置偏好（CPP）条件。WS 和纳曲酮在消退期（6-8 天）给药。观察 WS（650mg/kg）对酒精注射引发的小鼠再巩固行为（在酒精配对隔室中花费的时间）的影响。在实验 2 中，在标准测定的第一阶段（n=36）后，测量 WS（450mg/kg/）对酒精依赖大鼠（n=24）中中脑、纹状体和皮质（ng/gm）中 GABA 和多巴胺水平的影响。大鼠连续 15 天（间歇性接入模型）形成酒精依赖，同时给予 WS。第 16 天测量 GABA 和多巴胺水平。
WS 组在酒精配对隔室中花费的时间减少，与纳曲酮相似，与蒸馏水对照组相比差异显著（p<0.05）。酒精依赖大鼠的中脑、纹状体和皮质中 GABA 水平显著降低，多巴胺水平升高，与蒸馏水组相比。WS 和纳曲酮给药后，各组分离脑区的 GABA 升高，多巴胺降低（与酒精处理组相比，p<0.05）。
睡茄可保护动物免受复发，并对与酒精依赖相关的脑神经递质产生有益影响。该研究为其在酒精使用障碍中的潜在应用提供了充分的证据。
