Shah P C, Trivedi N A, Bhatt J D, Hemavathi K G
Department of Pharmacology, Medical College, Baroda.
Indian J Physiol Pharmacol. 2006 Oct-Dec;50(4):409-15.
The objective of the present study was to evaluate the antidepressant action of Withania somnifera (WS) as well as its interaction with the conventional antidepressant drugs and to delineate the possible mechanism of its antidepressant action using forced swimming model in mice. Effect of different doses of WS, fluoxetine and imipramine were studied on forced swimming test induced mean immobility time (MIT). Moreover effect of WS 100 mg/kg, i.p. was observed at different time intervals. Effect produced by combination of sub therapeutic doses of WS with imipramine (2.5 mg/kg, i.p.) as well as fluoxetine (2.5 mg/kg, i.p.) were also observed. Effect of WS (100 mg/kg, i.p.) as well as combination of WS (37.5 mg/kg, i.p.) with either imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.) were observed in mice pretreated with reserpine (2 mg/kg, i.p.) and clonidine (0.15 mg/kg, i.p.). Effects of prazosin (3 mg/kg, i.p.) or haloperidol (0.1 mg/kg, i.p.) pre-treatment were also observed on WS induced decrease in MIT. WS produced dose dependent decrease in MIT. Maximum effect in MIT was observed after 30 min of treatment with WS 100 mg/kg, i.p. Combination of WS (37.5 mg/kg, i.p.) with imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.) also produced significant decrease in the MIT. Clonidine and reserpine induced increase in MIT, was significantly reversed by treatment with WS (100 mg/kg, i.p.) as well as combination of WS (37.5 mg/kg, i.p.) with either imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.). Pre-treatment with prazosin but not haloperidol, significantly antagonized the WS (100 mg/kg, i.p.) induced decrease in MIT. It is concluded that, WS produced significant decrease in MIT in mice which could be mediated partly through a adrenoceptor as well as alteration in the level of central biogenic amines.
本研究的目的是评估睡茄（WS）的抗抑郁作用及其与传统抗抑郁药物的相互作用，并使用小鼠强迫游泳模型来阐明其抗抑郁作用的可能机制。研究了不同剂量的WS、氟西汀和丙咪嗪对强迫游泳试验诱导的平均不动时间（MIT）的影响。此外，还观察了腹腔注射100 mg/kg WS在不同时间间隔的作用。还观察了亚治疗剂量的WS与丙咪嗪（腹腔注射2.5 mg/kg）以及氟西汀（腹腔注射2.5 mg/kg）联合使用所产生的效果。在预先用利血平（腹腔注射2 mg/kg）和可乐定（腹腔注射0.15 mg/kg）处理的小鼠中，观察了WS（腹腔注射100 mg/kg）以及WS（腹腔注射37.5 mg/kg）与丙咪嗪（腹腔注射2.5 mg/kg）或氟西汀（腹腔注射2.5 mg/kg）联合使用的效果。还观察了哌唑嗪（腹腔注射3 mg/kg）或氟哌啶醇（腹腔注射0.1 mg/kg）预处理对WS诱导的MIT降低的影响。WS使MIT呈剂量依赖性降低。腹腔注射100 mg/kg WS处理30分钟后，观察到MIT的最大效应。WS（腹腔注射37.5 mg/kg）与丙咪嗪（腹腔注射2.5 mg/kg）或氟西汀（腹腔注射2.5 mg/kg）联合使用也使MIT显著降低。可乐定和利血平诱导的MIT增加，通过腹腔注射100 mg/kg WS以及WS（腹腔注射37.5 mg/kg）与丙咪嗪（腹腔注射2.5 mg/kg）或氟西汀（腹腔注射2.5 mg/kg）联合使用进行治疗后得到显著逆转。哌唑嗪预处理而非氟哌啶醇预处理显著拮抗了腹腔注射100 mg/kg WS诱导的MIT降低。得出的结论是，WS使小鼠的MIT显著降低，这可能部分通过α肾上腺素能受体以及中枢生物胺水平的改变介导。
