(+)3,4-Methylenedioxymethamphetamine ('ecstasy') transiently increases striatal 5-HT1B binding sites without altering 5-HT1B mRNA in rat brain

(+) 3,4-Methylenedioxymethamphetamine (MDMA) is a psychedelic drug of abuse that causes selective degeneration of serotonergic fibers of dorsal raphe neurons that project throughout the forebrain. Previous studies using pharm acological and behavioral approaches suggested that MDMA treatment leads to desensitization of 5-HT1B,, receptors. We proposed to test whether this oc curs by downregulation of 5-HT1B,, messenger RNA in dorsal raphe, striatum or CA1 hippocampal neurons and/or 5-HT1B,, binding site density in hippocam pus and basal ganglia. in Experiment 1, rats were treated with MDMA using s everal dosing protocols (2.5 or 10 mg kg(-1) day(-1) s.c. given a single ti me or twice daily for 4 days). The animals were killed 24 h after the last dose. [H-3]-citalopram binding to serotonin transporters in hippocampus was reduced in the high dose protocol, indicating degeneration of forebrain se rotonergic fibers. Despite the extensive reduction in serotonergic content, 5-HT1B,, mRNA did not change from control levels in any region when measur ed by in situ hybridization. [I-125]-lodocyanopindolol binding to 5-HT1B,, sites in hippocampus was also not changed. In Experiment II, high dose MDMA had no effect on 5-HT1B,, mRNA in any brain region either I or 14 days aft er treatment. However, [I-125]-iodocyanopindolol binding more than doubled in striatum 1 day after MDMA treatment but returned to control levels by 14 days. This may have been a transient compensation to early neuronal damage caused by MDMA exposure. These results suggest that previously described c hanges in 5-HT1B,, function following MDMA treatment involve only posttrans criptional changes in receptor regulation and do not alter 5-HT1B,, mRNA le vels.