Elevated dopamine D1 receptor availability in striatum of Göttingen minipigs after electroconvulsive therapy

Abstract

Electroconvulsive therapy (ECT), a direct form of brain stimulation, is an effective antidepressant. We hypothesized that the beneficial effects of ECT are mediated by increased dopaminergic neurotransmission, in which the baseline activity of D1 receptors may predict the response to ECT. We established a novel model of brain stimulation in Göttingen minipigs based on the protocol of ECT applied in humans. With positron emission tomography (PET), we determined a measure of dopaminergic neurotransmission with the dopamine D1 receptor antagonist [ 11 C]SCH23390. Seven minipigs were anesthetized and completed PET at baseline, prior to the onset of ECT treatment, and at 24–48 h and 8–10 days after the end of a clinical course of ECT, consisting of 10 ECT sessions over a 3.5-week period. In all pigs, the binding of [ 11 C]SCH23390 to striatal D1 receptors had increased by 24–48 h after ECT, and in most, binding returned towards baseline at 8–10 days. Increased binding was observed in inverse proportion to baseline binding rates. Increased binding to dopamine D1 receptors suggests facilitation of dopaminergic neurotransmission, which may contribute to the therapeutic effects of ECT. Importantly, the baseline binding capacity of D1 receptors predicts the magnitude of increased binding, up to a maximum binding capacity.