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-HT(2) receptors in rodents and humans. The consequences of another effective antidepressant treatment, electroconvulsive therapy (ECT), on 5-HT(2) receptors are less established.


METHODS
We studied the effects of a course of electroconvulsive shock (ECS) on 5-HT(2) receptor binding in nonhuman primates in vivo using positron emission tomography (PET) and the radiotracer [(18)F]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-HT(2) 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-HT(2) receptors and indicate that 5-HT(2) receptor downregulation may be a common effect of both pharmacologic and nonpharmacologic antidepressant treatments.
Strome
Elissa M
EM
Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada. strome@interchange.ubc.ca
Clark
Campbell M
CM
Zis
Athanasios P
AP
Doudet
Doris J
DJ
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004597:Electroshock / Q000379:methods*; D005462:Fluorine Radioisotopes / Q000494:pharmacology; D008253:Macaca mulatta; D008297:Male; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects / Q000528:radiation effects; D011744:Pyrimidinones / Q000494:pharmacology*; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism*; D012640:Seizures / Q000209:etiology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013997:Time Factors; D014055:Tomography, Emission-Computed / Q000379:methods
D005462:Fluorine Radioisotopes; D011744:Pyrimidinones; D044348:Receptors, Serotonin, 5-HT2; D012702:Serotonin Antagonists; C045359:setoperone