The Effects of MDMA ('Ecstasy') on Serotonin Transporter mRNA Expression in Rat Brain: a Model for Human Drug Abuse

Abstract

MDMA (3,4-methylenedioxymethamphetamine) is a class I illicit substance that has gained popularity as a 'rave' or party drug because of its ability to produce euphoria, reduce fears and increase sexual awareness. These effects are largely thought to be mediated through the serotonergic system in conjunction with the dopaminergic system. MDMA abuse causes axonal damage of the serotonergic pathways in rats, non human primates and humans. The number of MDMA users in New Zealand has doubled from 1.5% in 1998 to 3.4% in 2001, and continues to grow. The serotonin transporter is central to the neurotoxic effect of MDMA. Previous studies have shown changes in the serotonin transporter protein but to date only one study has looked at changes in mRNA expression. This study is one of the first to quantitatively analyze changes in serotonin transporter mRNA expression in response to MDMA pretreatment. Adult male Sprague Dawley rats were given 4 injections (10 mg/kg) of MDMA or saline (control) at two hour intervals and sacrificed two weeks later. The brains were analyzed using quantitative fluorescence in situ hybridization (FISH) to measure changes in serotonin transporter (SERT) mRNA throughout the brain. No difference was found in SERT mRNA expression between saline and MDMA treated rats in any of the 13 nuclei analysed in this study. The 13 nuclei analysed could be divided into 3 distinct levels of SERT mRNA expression, further expanding on the findings of previous studies which only distinguish the dorsal and median raphe nuclei from all other established SERT mRNA expressing nuclei. The distribution of SERT mRNA expression found in this study has shown that FISH, as expected, is more sensitive than RISH and the results obtained in this study are consistent with distribution patterns established by RT-PCR methods. Two novel SERT mRNA expressing nuclei (the inferior olive and the lateral anterior olfactory nucleus) have also been identified in this study.