Potentiation of (DL)‐3,4‐methylenedioxymethamphetamine (MDMA)‐induced toxicity by the serotonin 2A receptior partial agonist d‐lysergic acid diethylamide (LSD), and the protection of same by the serotonin 2A/2C receptor antagonist MDL 11,939

Abstract

To elucidate the role of the serotonin (5-HT)2A/2C receptors in 3,4-methylenedioxymethamphetamine (MDMA)-induced neurotoxicity, MDMA was administered to rats and the presence of the serotonin transporter (5-HTT) was assessed at the protein level with immunohistochemistry (IHC), and the RNA level with a Northern blotting technique. d-lysergic acid diethylamide (LSD) and MDL 11,939 were given in conjunction with MDMA in order to assess the importance of 5-HT receptors in MDMA-induced neurotoxicity. The hypothesis is that the MDMA + LSD-treated animals should have more neurotoxicity as measured by loss of 5-HTTs compared to the MDMA-treated animals. Moreover, the loss of 5-HTTs should be attenuated in animals given the combination of MDMA + MDL 11,939, as the latter drug is a selective 5-HT2A/2C antagonist. The results showed that MDMA-induced neurotoxicity was dose dependently increased by LSD. Moreover, the drug MDL 11,939 attenuated MDMA-induced neurotoxicity, suggesting that 5-HT2A/2C receptors are involved in MDMA-induced neurotoxicity.