Behavioral and neurochemical effects of orally administered MDMA in the rodent and nonhuman primate.
MDMA (methylenedioxymethamphetamine) is a recreational drug of abuse known as "Ecstasy" which markedly decreases regional brain serotonin (5-HT) content and produces 5-HT nerve terminal degeneration in forebrain areas of the rat. In order to determine the acute and chronic behavioral effects of MDMA, adult rats were given MDMA at 0, 5 or 10 mg/kg, po for 4 consecutive days. Alternatively, parachloroamphetamine (PCA) at 5 mg/kg was administered under the same regimen. Within 30 min after the first dose, the MDMA-treated rats exhibited the serotonin motor syndrome consisting of straub tail and splayed hindlimbs comparable to that seen in the PCA-treated rats. This serotonin motor syndrome, with a duration of about 2 hr, was less pronounced after subsequent doses. At 2-4 wk after the last dose, no significant differences between control and treated rats were seen in emergence, hot plate response, auditory startle response or complex maze behavior even though a significant dose-related decrease (50%) in 5-HT concentration was observed in the frontal cortex and hippocampus of these rats 4 wks after the last dose. Adult female monkeys dosed po with 5 or 10 mg/kg of MDMA twice/day for 4 consecutive days demonstrated no spontaneous behavioral changes or weight loss compared to controls, but forebrain 5-HT concentration was reduced by 80% 1 mon after dosing. These data indicate that at doses only 2-3 times the human dose, MDMA produces significant forebrain 5-HT decreases but does not produce detectable residual behavioral alterations as assessed by these behavioral paradigms.
Slikker
W
W
Division of Reproductive and Developmental Toxicology, National Center for Toxicological Research, Jefferson, Arkansas 72079.
Holson
R R
RR
Ali
S F
SF
Kolta
M G
MG
Paule
M G
MG
Scallet
A C
AC
McMillan
D E
DE
Bailey
J R
JR
Hong
J S
JS
Scalzo
F M
FM
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives / Q000633:toxicity*; D000662:Amphetamines / Q000633:toxicity*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015306:Biogenic Monoamines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D005260:Female; D008253:Macaca mulatta; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D013216:Reflex, Startle / Q000187:drug effects; D012737:Sex Factors; D001615:beta-Endorphin / Q000378:metabolism; D010133:p-Chloroamphetamine / Q000633:toxicity
D000662:Amphetamines; D015306:Biogenic Monoamines; D015104:3,4-Methylenedioxyamphetamine; D001615:beta-Endorphin; D010133:p-Chloroamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine