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 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 D1 and D2 receptors at pubescence, or other factors related to drug metabolism.