MDMA (‘ecstasy’) enhances basal acetylcholine release in brain slices of the rat striatum
European Journal of Neuroscience April 1, 2000 H. S. Fischer, Gerald Zernig, Dieter S. Schatz et al. 54 citations
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.