Glucocorticoids and 3,4-methylenedioxymethamphetamine (MDMA)-induced neurotoxicity.
The present study was carried out in order to explore the role of glucocorticoids in 3,4-methylenedio-xymethamphetamine (MDMA)-induced neurotoxicity of the central serotonergic system. The activity of tryptophan hydroxylase (TPH) was used as an index of this drug-induced neuronal degeneration. One week after a single high dose of MDMA (20 mg/kg), a significant decrease in the enzyme activity was measured in both the frontal cortex and hippocampus. Adrenalectomy (ADX) attenuated or blocked this decrease in TPH activity in the hippocampus but not in the frontal cortex. This protective effect of ADX on hippocampal serotonergic neurons disappeared with concurrent administration of corticosterone (CORT) and MDMA administration. The long-term MDMA-induced decreases in hippocampal serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were similarly affected by CORT replacement. However, ADX did not alter the short-term decline in hippocampal TPH activity and 5-HT concentrations measured 3 h after a single dose of MDMA (10 mg/kg s.c.). This study suggests that CORT play a role in the development of neurotoxicity induced by MDMA in the hippocampal serotonergic system, but may be less important in other brain structures.
Johnson
M
M
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112.
Stone
D M
DM
Bush
L G
LG
Hanson
G R
GR
Gibb
J W
JW
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives / Q000633:toxicity*; D000315:Adrenalectomy; D000662:Amphetamines / Q000633:toxicity*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D003345:Corticosterone / Q000494:pharmacology; D005938:Glucocorticoids / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009422:Nervous System Diseases / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000378:metabolism
D000662:Amphetamines; D005938:Glucocorticoids; D012701:Serotonin; D015104:3,4-Methylenedioxyamphetamine; D006897:Hydroxyindoleacetic Acid; D014365:Tryptophan Hydroxylase; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D003345:Corticosterone