(Ecstasy) Induces c-fos-Like Protein and mRNA in Rat Organotypic Dorsal Striatal Slices

3,4-Methylenedioxymetamphetamine (MDMA, ‘‘ecstasy’’) is an increasingly abused drug, which has significant effects on the dopamine system in the striatum. The isolated single organotypic slice model allows investigation of the effects of drugs of abuse on the expression of transcription factors in the striatum without dopaminergic and glutamatergic interactions. In this study the effects of MDMA on the expression of c-fos mRNA by in situ hybridization as well as the c-fos-like protein by immunohistochemistry in isolated dorsal striatum was investigated. It was shown that 100 μM MDMA induced c-fos mRNA expression 30 min after treatment. Expression of c-fos-like protein was transiently detected 3 h afterwards. The c-fos expression was inhibited by MK 801 and metoclopramide, indicating the involvement of dopaminergic D2 receptors and glutamatergic NMDA receptors. The dopaminergic D1 receptor antagonist SCH 23390 did not affect c-fos expression. We conclude that MDMA treatment leads to the induction of c-fos expression in isolated rat striatal slices. This effect is independent of extrinsic neuronal circuitry and seems to be associated with direct interactions between MDMAand the dopamine/glutamate receptor system. Synapse 36:75–83, 2000. r 2000 Wiley-Liss, Inc.