THE EFFECT OF MDMA (3,4-METHYLENEDIOXYMETHAMPHETAMINE) ON THE 5-HT SYNTHESIS RATE IN THE RAT-BRAIN - AN AUTORADIOGRAPHIC STUDY

The effect of MDMA (3,4-methylenedioxymethamphetamine), a psychotropic amphetamine derivative, treatment on the rate of serotonin (5-hydroxy tryptamine; 5-HT) synthesis in the rat brain was studied by autoradiog raphy using alpha-[C-14]-methyl-L-tryptophan method. Three different t reatment protocols were compared to the control (saline) treated rats: (1) rats treated twice with 10 mg/kg every 12 h (20 mg/kg total) and injected tracer for the synthesis measurements 15 h later; (2) rats tr eated with four injections of 5 mg/kg every 12 h (20 mg/kg total) and injected tracer for the synthesis measurement 17 h after the last dose ; and (3) rats given eight injections of 5 mg/kg every 12 h for four d ays (40 mg/kg) and used in the synthesis study 14 days after the last dose. Results showed a significant decrease in the rate of synthesis i n the majority of cerebral structures examined in the 10 mg/kg group. In contrast the group receiving the same total amount (20 mg/kg) of MD MA but over two days (4 x 5 mg/kg) showed a significant increase in 5- HT synthesis in comparison to controls. The 5-HT synthesis rates measu red 14 days after the last dose (four days, 8 x 5 mg/kg) were signific antly reduced. The findings suggest that MDMA can produce either an in crease or a decrease in the 5-HT synthesis a short time after a total dose of 20 mg/kg depending on the dose fractionation. However, 14 days after total dose of 40 mg/kg given over four days the synthesis rate was significantly reduced in many brain structures. The latter suggest s a possible effect of the MDMA neurotoxicity on the serotonergic neur ons, in addition to a possible influence on 5-HT sysnthesis via a feed back mechanism. (C) 1998 Elsevier Science B.V. All rights reserved.