Electroacupuncture combined with clomipramine enhances antidepressant effect in rodents

Abstract

The present study was designed to evaluate the antidepressant effect of electroacupuncture (EA) and the potential additive or synergistic effects of EA and clomipramine (CLO, a tricyclic antidepressant) in the mouse forced swimming test (FST) and chronic mild stress (CMS) induced depression-model rats. The FST is an antidepressant screening procedure performed initially to observe the immediate effects of EA and/or CLO on the immobility time. CLO (2.5, 5, 10, 20 and 60mg/kg intraperitoneally) were administered at 23, 6 and 1h respectively prior to each test. EA was given at the 'Bai-Hui' (Du 20) and unilateral 'An-Mian' (EX 17) acupoints 1h before each test. Immobility time was significantly reduced by EA and CLO at 2.5, 5, 10, 20 or 60mg/kg, respectively. EA combined with 2.5mg/kg CLO exhibited additive effects on the immobility time. In addition, rats were exposed chronically (1st-11th week) to a variety of mild unpredictable stressors. Depressed mood and anhedonia were recognized as a decrease in sucrose intake in the CMS rats. CLO at 2.5, 5mg/kg and EA at the same acupoints and parameters were administrated on the CMS rats once every other day for 6 weeks (5th-11th week). The intake of 1% sucrose solution was reduced by CMS, which was restored to normal level after 6 weeks treatment with 5mg/kg CLO or EA combined with 2.5mg/kg CLO. However, neither the sucrose intake nor the sucrose preference in the depressive rats was significantly changed by the treatment with EA or 2.5mg/kg CLO alone. These results demonstrated that EA combined with CLO at low doses has an additive or synergistic antidepressant action, and this combination may provide an effective strategy for depression management.