In nowadays, although the development of new anti-depressant drugs had made great progress in recent two decades for the treatment of this disease, the overall result for the current treatment of depression is less ideal. What is more, about 30% of patients suffering from a major depressive disorder do not respond to the established pharmacological treatments.

In another avenue, as an non-invasive, non-injury alternative therapy, acupuncture has been proven to be an effective treatment for depression ( for review see, Can J Psychiatry. 2012 Jul; 57(7): 397-405 J Affect Disord. 2010 Jul; 124(1-2): 9-21. J. Affect Disord. 2008 Dec; 111(2-3): 125-34, J Affect Disord. 2007 Jan; 97(1-3): 13-22)

However the mechanism is still largely unknown. Recently, people realize that the acupuncture stimulation in the body, especially in the ear may activate the vagus nerve. Activation of the vagus nerve may result in the release of noradrenaline and serotonin, which are two most important neurotransmitters that are decreased in the depressant.

 As we all know that the antidepressant drugs cause noradrenaline and serotonin increases too.  So the question is why acupuncture-induced noradrenaline and serotonin increases produce an antidepressant effect, while drug-induced noradrenaline and serotonin increases remain without an effect in this patient population.

  Dorr and Debonnel from Department of Psychiatry, McGill University suggested that antidepressant agents and VNS enhance the noradrenergic and serotonergic neurotransmission in a different way (Manta et al., 2009). Antidepressant drugs that increase the noradrenaline and/or serotonin concentrations initially decrease the firing rate of the Locus coeruleus (LC) and dorsal raphe nucleus (DRN) neurons due to binding of the neurotransmitters to the somatodendritic autoreceptors on these neurons (Pineyro and Blier, 1999).  Long-term treatment restores the firing activity back to baseline due to desensitization of these receptors while keeping high synaptic availability of noradrenaline and/or serotonin. Antidepressant treatments thus increase the efficacy of the noradrenergic and/or serotonergic neurotransmission via an increase in neurotransmitter release and altered sensitivity of inhibitory autoreceptors (reviewed in (Blier, 2003)).

VNS on the other hand enhances the noradrenergic and serotonergic neurotransmission by inducing an increase in the firing rate of both the LC and the DRN neurons above their baseline activity (Manta et al., 2009, 2012; Dorr and Debonnel, 2006). Moreover, VNS represents the first antidepressant treatment able to induce increased firing activity of both serotonergic and noradrenergic neurons ( Adrienne E. Dorr and Guy Debonne, 2006).