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  • Title: Increased CRE-binding activity and tryptophan hydroxylase mRNA expression induced by 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in the rat frontal cortex but not in the hippocampus.
    Author: García-Osta A, Del Río J, Frechilla D.
    Journal: Brain Res Mol Brain Res; 2004 Jul 26; 126(2):181-7. PubMed ID: 15249142.
    Abstract:
    A single administration of either 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") or p-chloroamphetamine (PCA) produced a rapid and marked reduction of serotonin (5-HT) content in rat frontal cortex and hippocampus. In the cortex of MDMA-treated rats, 5-HT levels returned to control values 48 h after drug administration. This recovery was correlated with an induction of CRE-binding activity and an enhanced expression of tryptophan hydroxylase (TPH) mRNA, the rate-limiting enzyme in 5-HT biosynthesis, suggesting that MDMA may up-regulate the TPH gene through a CREB-dependent mechanism. In the cortex of PCA-treated rats, neither a recovery of 5-HT levels nor changes in DNA-binding or TPH mRNA were found at the same time point. In the hippocampus of rats receiving either PCA or MDMA a decrease in TPH mRNA levels was found at all times, along with a reduced CRE-binding at the 8-h time point. The results show region-specific effects of MDMA. In the frontal cortex, the increased TPH expression suggests a compensatory response to MDMA-induced loss of serotonergic function.
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