Electroacupuncture combined with clomipramine enhances antidepressant effect in rodents

Department of Integrative Medicine and Neurobiology, Institute of Acupuncture Research (WHO Collaborating Center for Traditional Medicine), Shanghai Medical College, Fudan University, Shanghai 200032, China.
Neuroscience Letters (Impact Factor: 2.03). 07/2007; 421(1):5-9. DOI: 10.1016/j.neulet.2007.02.052
Source: PubMed


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.

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    • "Reduced preference for sucrose solution over water is a widely used animal model of anhedonia. Anhedonia in both experimental models and depressed patients implies a defective reward system [37] that can be effectively treated by the tricyclic antidepressants (TCAs) [38],[39]. The major difference between tree shrews and rodents is the concentration of sucrose needed to demonstrate stress-induced anhedonia. "
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    ABSTRACT: Chronic stress is the major cause of clinical depression. The behavioral signs of depression, including anhedonia, learning and memory deficits, and sleep disruption, result from the damaging effects of stress hormones on specific neural pathways. The Chinese tree shrew (Tupaia belangeri chinensis) is an aggressive non-human primate with a hierarchical social structure that has become a well-established model of the behavioral, endocrine, and neurobiological changes associated with stress-induced depression. The tricyclic antidepressant clomipramine treats many of the core symptoms of depression in humans. To further test the validity of the tree shrew model of depression, we examined the effects of clomipramine on depression-like behaviors and physiological stress responses induced by social defeat in subordinate tree shrews. Social defeat led to weight loss, anhedonia (as measured by sucrose preference), unstable fluctuations in locomotor activity, sustained urinary cortisol elevation, irregular cortisol rhythms, and deficient hippocampal long-term potentiation (LTP). Clomipramine ameliorated anhedonia and irregular locomotor activity, and partially rescued the irregular cortisol rhythm. In contrast, weight loss increased, cortisol levels were even higher, and in vitro LTP was still impaired in the clomipramine treatment group. These results demonstrate the unique advantage of the tree shrew social defeat model of depression.
    Full-text · Article · Dec 2013 · PLoS ONE
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    • "In the present study, we found that sucrose preference and immobility time in the model rats were not significantly affected by EA treatment, even though there was a tendency of increase or reduction after 3 weeks of stimulation. These results are in agreement with several previous studies that were also performed on the CUS model rats [54–56]. Liu and his colleagues demonstrated that 3 weeks of EA stimulation produced a significant increase in the number of crossing in the OFT and a nonsignificant increase in the sucrose intake [55]. "
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    ABSTRACT: Currently, antidepressants are the dominative treatment for depression, but they have limitations in efficacy and may even produce troublesome side effects. Electroacupuncture (EA) has been reported to have therapeutic benefits in the treatment of depressive disorders. The present study was conducted to determine whether EA could enhance the antidepressant efficacy of a low dose of citalopram (an SSRI antidepressant) in the chronic unpredictable stress-induced depression model rats. Here, we show that a combined treatment with 2 Hz EA and 5 mg/kg citalopram for three weeks induces a significant improvement in depressive-like symptoms as detected by sucrose preference test, open field test, and forced swimming test, whereas these effects were not observed with either of the treatments alone. Further investigations revealed that 2 Hz EA plus 5 mg/kg citalopram produced a remarkably increased expression of BDNF and its receptor TrkB in the hippocampus compared with those measured in the vehicle group. Our findings suggest that EA combined with a low dose of citalopram could produce greater therapeutic effects, thereby, predictive of a reduction in drug side effects.
    Full-text · Article · May 2013 · Evidence-based Complementary and Alternative Medicine
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    • "Recently, evidence from clinical and experimental studies have indicated that acupuncture may alleviate the symptoms of depression [5] [6] [7]. However, the underlying mechanism remains unknown. "
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    ABSTRACT: Adenylyl cyclase (AC)-cyclic adenosine monophosphate (cAMP)-cAMP-dependent protein kinase A (PKA) cascade is considered to be associated with the pathogenesis and treatment of depression. The present study was conducted to explore the role of the cAMP cascade in antidepressant action of electroacupuncture (EA) treatment for chronic mild stress (CMS)-induced depression model rats. The results showed that EA improved significantly behavior symptoms in depression and dysfunction of AC-cAMP-PKA signal transduction pathway induced by CMS, which was as effective as fluoxetine. Moreover, the antidepressant effects of EA rather than Fluoxetine were completely abolished by H89, a specific PKA inhibitor. Consequently, EA has a significant antidepressant treatment in CMS-induced depression model rats, and AC-cAMP-PKA signal transduction pathway is crucial for it.
    Full-text · Article · May 2012 · Evidence-based Complementary and Alternative Medicine
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