Electroconvulsive therapy: a novel hypothesis for the involvement of purinergic signalling

Abstract

It is proposed that ATP is released from both neurons and glia during electroconvulsive therapy (ECT) and that this leads to reduction of depressive behaviour via complex stimulation of neurons and glia directly via P2X and P2Y receptors and also via P1 receptors after extracellular breakdown of ATP to adenosine. In particular, A(1) adenosine receptors inhibit release of excitatory transmitters, and A(2A) and P2Y receptors may modulate the release of dopamine. Sequential ECT may lead to changes in purinoceptor expression in mesolimbic and mesocortical regions of the brain implicated in depression and other mood disorders. In particular, increased expression of P2X7 receptors on glial cells would lead to increased release of cytokines, chemokines and neurotrophins. In summary, we suggest that ATP release following ECT involves neurons, glial cells and neuron-glial interactions acting via both P2 and after breakdown to adenosine via P1 receptors. We suggest that ecto-nucleotidase inhibitors (increasing available amounts of ATP) and purinoceptor agonists may enhance the anti-depressive effect of ECT.

Fig. 1

Schematic hypothesis of purinergic signalling in electroconvulsive therapy. During electroconvulsive therapy, ATP is released from astrocytes, neurons and vascular endothelial cells. The ATP acts upon P2X7, P2Y₁ receptors and also P1 receptors after the extracellular breakdown of ATP to ADO. Activation of P2X7 and ADO receptors on glial cells results in increased release of cytokines, chemokines and neurotrophins, which act upon neurons in regions involved in the control of mood and motivation. Stimulation of P2Y receptors may modulate the release of dopamine (DA), glutamate (Glut) and nitric oxide (NO) all implicated in control of mood