Electroconvulsive shock decreases binding to 5-HT2 receptors in nonhuman primates: An in vivo positron emission tomography study with [18F]setoperone

Background Dysfunction within the serotonin (5-HT) system plays a major role in the etiology of human depression, and treatment with antidepressant drugs downregulates 5-HT2 receptors in rodents and humans. The consequences of another effective antidepressant treatment, electroconvulsive therapy (ECT), on 5-HT2 receptors are less established. Methods We studied the effects of a course of electroconvulsive shock (ECS) on 5-HT2 receptor binding in nonhuman primates in vivo using positron emission tomography (PET) and the radiotracer [18F]setoperone. Seven adult male rhesus monkeys received two bilateral ECS treatments per week for 3 weeks; PET scans were performed before treatment, and 24 hours, 1 week, and 4–6 weeks after completion of the course of ECS. Regions of interest were placed throughout the cortex, and the data analyzed as the ratio of specific:nonspecific radioactivity accumulation, with the cerebellum used as a measure of nonspecific binding. Results Serotonin 5-HT2 binding was significantly decreased at 24 hours and 1 week post-ECS, but returned to baseline 4–6 weeks posttreatment. Conclusions These results show for the first time in a primate species that chronic ECS decreases binding to 5-HT2 receptors and indicate that 5-HT2 receptor downregulation may be a common effect of both pharmacologic and nonpharmacologic antidepressant treatments.