Electroconvulsive therapy alters dopamine signaling in the striatum of non-human primates

Abstract

Electroconvulsive therapy (ECT) is one of the most effective therapies for depression and has beneficial motor effects in parkinsonian patients. However, little is known about the mechanisms of therapeutic action of ECT for either condition. The aim of this work was to explore the impact of ECT on dopaminergic function in the striatum of non-human primates. Rhesus monkeys underwent a course of six ECT treatments under a human clinical protocol. Longitudinal effects on the dopaminergic nigrostriatal system were studied over 6 weeks using the in vivo capabilities of positron emission tomography (PET). PET scans were performed prior to the onset of ECT treatments and at 24-48 h, 8-10 days, and 6 weeks after the final ECT treatment. Early increases in dopamine transporter and vesicular monoamine transporter 2 binding returned to baseline levels by 6 weeks post-ECT. Transient increases in D1 receptor binding were also observed, whereas the binding potential to D2 receptors was unaltered. The increase in dopaminergic neurotransmission suggested by our results may account in part for the therapeutic effect of ECT in mood disorders and Parkinson's disease.

Figure 1

Graphs showing the binding potentials (BP_ND) for the presynaptic (methylphenidate (DAT) and dihydrotetrabenazine (VMAT2)) and postsynaptic (SCH23390 (DA D1) and raclopride (DA D2)) tracers at baseline, 1–2 days, 8–10 days, and 6 weeks after the end of a course of ECT. Note the quadratic shape of the response of the presynaptic tracers (inverted U shape).

Figure 2

Graphs showing the estimated marginal means obtained from the statistical analysis for the striatum with all four tracers. The x axis shows the four times considered in the analysis: 1=baseline pre-ECT, 2=1–2 days, 3=8–10 days, and 4=6 weeks post-ECT. Note the inverted U shape for MP and DTBZ.