Potentiation of 3,4-methylenedioxymethamphetamine-induced dopamine release and serotonin neurotoxicity by 5-HT2 receptor agonists.
European journal of pharmacology – November 03, 1994
Source: PubMed
Summary
Administering 5-HT2 receptor agonists DOI (2 mg/kg) and 5-MeODMT (15 mg/kg) significantly enhanced MDMA-induced dopamine release in the striatum of rats, as measured by in vivo microdialysis. While MDMA alone (10 mg/kg) led to a minor decrease in serotonin (5-HT) levels after seven days, combining DOI with MDMA resulted in a significant reduction of 5-HT compared to those treated with MDMA or controls. This highlights the crucial role of 5-HT2 receptors in both immediate dopamine spikes and long-term serotonin depletion following MDMA use.
Abstract
The effects of the 5-HT2 receptor agonists 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) on 3,4-methylenedioxymethamphetamine (MDMA)-induced dopamine release and 5-HT depletion in the striatum were studied. The MDMA-induced increase in the extracellular concentration of dopamine in the striatum was enhanced significantly in rats treated with either DOI (2 mg/kg, ip.) or 5-MeODMT (15 mg/kg, ip.), as assessed using in vivo microdialysis. Neither DOI nor 5-MeODMT alone altered the extracellular concentration of dopamine in the striatum. The striatal concentration of 5-HT was decreased, but not significantly, 7 days following a single administration of MDMA (10 mg/kg, sc.). However, 7 days following the concomitant treatment with DOI and MDMA the striatal concentration of 5-HT was significantly less than that in rats treated with MDMA alone or the vehicle-treated controls. It is concluded that activation of 5-HT2 receptors is an important determinant of the acute increase in extracellular dopamine and, consequently, the long-term depletion of brain 5-HT produced by MDMA.