The involvement of dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) in blocking the therapeutic effect of electroconvulsive shocks in an animal model of depression.
Depressed patients with resistance to electroconvulsive treatment (ECT) had high basal serum levels of dehydroepiandrosterone (DHEA) sulfate (DHEAS). To clarify the role of DHEA/S in the ECT resistance, Flinder Sensitive Line (FSL) rats, which are a genetic animal model of depression, were injected i.p. with 2 mg/kg DHEA daily for 13 days to overload their serum and brain DHEA/S levels. Thereafter, rats were exposed to electroconvulsive shock (ECS), which is analogue to ECT in humans. Both ECS and DHEA displayed an antidepressive-like effect, as assessed by immobility time in forced swim test. However, combined DHEA and ECS treatment abolished these antidepressive-like effects. In addition, the levels of neurosteroids, corticosterone and adrenocorticotropin in selected brain regions were evaluated and compared to serum levels. The present study supports our assumption that high basal levels of DHEA/S play a role in the resistance to ECS and maybe ECT in humans.
Maayan
Rachel
R
Biological Psychiatry Laboratory, Felsenstein Medical Research Center and Sackler Faculty of Medicine, Tel Aviv University, Beilinson Campus, Petah Tikva, Israel.
Morad
Oren
O
Dorfman
Pnina
P
Overstreet
David H
DH
Weizman
Abraham
A
Yadid
Gal
G
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D003600:Cytosol / Q000201:enzymology; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood / Q000378:metabolism*; D003863:Depression / Q000097:blood / Q000235:genetics / Q000628:therapy*; D004597:Electroshock; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011284:Pregnenolone / Q000097:blood / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015238:Sulfotransferases / Q000378:metabolism
D009419:Nerve Tissue Proteins; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D011284:Pregnenolone; D000324:Adrenocorticotropic Hormone; D015238:Sulfotransferases; C044251:steroid sulfotransferase; D006854:Hydrocortisone