Long-term alteration in the central monoaminergic systems of the rat by 2,4,5-trihydroxyamphetamine but not by 2-hydroxy-4,5-methylenedioxymethamphetamine or 2-hydroxy-4,5-methylenedioxyamphetamine.
The long-term effects of three metabolites of 3,4-methylenedioxymethamphetamine (MDMA) on the central monoaminergic systems of the rat were examined. Seven days after the intracerebroventricular administration of 0.25 and 0.5 mumol 2,4,5-trihydroxyamphetamine, hippocampal tryptophan hydroxylase (TPH) activity was reduced to 5 and 1% of control, respectively, while norepinephrine (NE) concentration was depressed to 10 and 18% of control. These two respective dosages also decreased striatal tyrosine hydroxylase (TH) activity to 67 and 10% of control, respectively, while nigral TH activity was reduced to 59 and 20% of control. Striatal TPH activity was reduced to 74 and 81% of control, respectively, while the activity in the dorsal and median raphe remained unaltered. The intracerebroventricular administration of 1 mumol 2-hydroxy-4,5-methylenedioxymethamphetamine (6-OH-MDMA) failed to alter TPH activity, TH activity or NE concentration after 14 days. In contrast, 1 mumol of 2-hydroxy-4,5-methylenedioxyamphetamine (6-OH-MDA) induced a 30% increase in striatal TPH activity and a 50% increase in nigral TH activity. The study of the formation of 2,4,5-trihydroxyamphetamine after MDMA treatment may provide insight as to how MDMA destroys serotonergic nerve terminals.
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112.
I
I
Elayan
J W
JW
Gibb
G R
GR
Hanson
R L
RL
Foltz
H K
HK
Lim
M
M
Johnson
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D000662:Amphetamines / Q000633:toxicity; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000032:analysis; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D000662:Amphetamines; C074079:2,4,5-trihydroxyamphetamine; C073631:6-hydroxy-N-methyl-3,4-methylenedioxyamphetamine; C078244:2-hydroxy-4,5-methylenedioxyamphetamine; D012701:Serotonin; D015104:3,4-Methylenedioxyamphetamine; D014446:Tyrosine 3-Monooxygenase; D014365:Tryptophan Hydroxylase; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine; D009638:Norepinephrine