MDMA (ecstasy) effects in pubescent rats: Males are more sensitive than females

In Experiment 1, we assessed the effects of 3,4-methylenedioxymethamphetamine (MDMA) on locomotor activity in pubescent male and female Long–Evans rats. Thirty-nine day old rats were injected ip with 10 mg/kg of MDMA (ambient temperature 25 °C) three times at 2 h intervals. Initially, females showed...

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Published in:Pharmacology, biochemistry and behavior biochemistry and behavior, 2005-07, Vol.81 (3), p.635-644
Main Authors: Koenig, Julie, Lazarus, Christine, Jeltsch, Hélène, Ben Hamida, Sami, Riegert, Céline, Kelche, Christian, Jones, Byron C., Cassel, Jean-Christophe
Format: Article
Language:English
Subjects:
3,4-Dihydroxyphenylacetic Acid - metabolism
Animals
Biological and medical sciences
Body Temperature - drug effects
Brain - drug effects
Brain - metabolism
Chromatography, High Pressure Liquid
Dopamine - metabolism
Dose-Response Relationship, Drug
Ecstasy
Female
Hydroxyindoleacetic Acid - metabolism
Lethality
Life Sciences
Locomotor activity
Male
MDMA
Medical sciences
Motor Activity - drug effects
N-Methyl-3,4-methylenedioxyamphetamine - pharmacology
N-Methyl-3,4-methylenedioxyamphetamine - toxicity
Neurobiology
Neurons and Cognition
Norepinephrine - metabolism
Pubescence
Random Allocation
Rats
Rats, Long-Evans
Serotonin - metabolism
Sex Factors
Sexual dimorphism
Sexual Maturation - physiology
Survival Rate
Time Factors
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Summary:In Experiment 1, we assessed the effects of 3,4-methylenedioxymethamphetamine (MDMA) on locomotor activity in pubescent male and female Long–Evans rats. Thirty-nine day old rats were injected ip with 10 mg/kg of MDMA (ambient temperature 25 °C) three times at 2 h intervals. Initially, females showed greater locomotor activation by the drug than males, however after the second injection, males showed greater hyperlocomotion. After the third injection, 3 of 10 females and all of the males died. In the surviving females, we observed serotonin depletion in cortex and hippocampus, but catecholaminergic markers were unaltered. In Experiment 2, male and female rats were repeatedly injected with saline or 2, 5 or 10 mg/kg MDMA and body temperature was measured (ambient temperature 21.5 °C). After the third injection of 10 mg/kg MDMA, the MDMA-induced hyperthermia was greater in males than in females (about + 0.8 °C); at the lower dose, no difference was observed. Probably because of the lower ambient temperature, only 1 female and 2 males succumbed to the MDMA treatment, and MDMA induced less serotonin depletion than in the first experiment, with no difference between females and males. Thus, pubescent males appear to be more sensitive than females to locomotor and hyperpyretic effects of MDMA. This sex-dependent effect, which is at variance with previously reported dimorphisms in psychostimulant effects, is discussed in terms of possible differences in dopamine D 1 and D 2 receptors at pubescence, or other factors related to drug metabolism.
ISSN:0091-3057
1873-5177
DOI:10.1016/j.pbb.2005.04.014