MDMA (ecstasy) is a common illegal drug among European adolescents who are typically inexperienced with hard drugs like cocaine. In rats, the reinforcing effect of intravenously self-administered MDMA did not differ between drug-naive animals and those previously trained with cocaine. MDMA sensitized rats to its own rate-increasing effect but not to that of cocaine. No carryover of cocaine's reinforcing effect to MDMA was observed, indicating that MDMA and cocaine produce distinct interoceptive stimuli in rats.
MDMA (ecstasy) increases the release of the neurotransmitter acetylcholine in rat striatal brain slices in a dose-dependent manner, with a half-maximal effect at about 30 µM. This effect requires calcium and is blocked by tetrodotoxin, indicating it depends on neuronal firing. Blocking glutamate, dopamine D2, serotonin 5-HT1, 5-HT2, 5-HT3C, or muscarinic acetylcholine receptors did not alter MDMA's effect, but blocking histamine H1 receptors completely abolished the acetylcholine release. The findings suggest MDMA directly activates histamine H1 receptors to stimulate striatal cholinergic neurons, revealing a previously unknown neurochemical pathway for MDMA's acute effects.