Studies on the role of dopamine in the degeneration of 5‐HT nerve endings in the brain of Dark Agouti rats following 3,4‐methylenedioxymethamphetamine (MDMA or ‘ecstasy’) administration
British Journal of Pharmacology – February 01, 1999
Source: OpenAlex
Summary
MDMA, commonly known as ecstasy, dramatically increases dopamine levels in the brain—by an astonishing 800% after administration. In a study involving Dark Agouti rats, administering haloperidol before and after MDMA reduced neurotoxic loss of serotonin seven days later. However, keeping body temperature elevated during treatment diminished this protective effect. Interestingly, while L-DOPA enhanced dopamine levels post-MDMA, it did not affect neurodegeneration. These findings suggest that MDMA's impact on dopamine may stem from its influence on re-uptake and serotonin release rather than direct neurotoxicity.
Abstract
We investigated whether dopamine plays a role in the neurodegeneration of 5‐hydroxytryptamine (5‐HT) nerve endings occurring in Dark Agouti rat brain after 3,4‐methylenedioxymethamphetamine (MDMA or ‘ecstasy’) administration. Haloperidol (2 mg kg −1 i.p.) injected 5 min prior and 55 min post MDMA (15 mg kg −1 i.p.) abolished the acute MDMA‐induced hyperthermia and attenuated the neurotoxic loss of 5‐HT 7 days later. When the rectal temperature of MDMA+haloperidol treated rats was kept elevated, this protective effect was marginal. MDMA (15 mg kg −1 ) increased the dopamine concentration in the dialysate from a striatal microdialysis probe by 800%. L ‐DOPA (25 mg kg −1 i.p., plus benserazide, 6.25 mg kg −1 i.p.) injected 2 h after MDMA (15 mg kg −1 ) enhanced the increase in dopamine in the dialysate, but subsequent neurodegeneration was unaltered. L ‐DOPA (25 mg kg −1 ) injected before a sub‐toxic dose of MDMA (5 mg kg −1 ) failed to induce neurodegeneration. The MDMA‐induced increase in free radical formation in the hippocampus (indicated by increased 2,3‐ and 2,5‐dihydroxybenzoic acid in a microdialysis probe perfused with salicylic acid) was unaltered by L ‐DOPA. The neuroprotective drug clomethiazole (50 mg kg −1 i.p.) did not influence the MDMA‐induced increase in extracellular dopamine. These data suggest that previous observations on the protective effect of haloperidol and potentiating effect of L ‐DOPA on MDMA‐induced neurodegeneration may have resulted from effects on MDMA‐induced hyperthermia. The increased extracellular dopamine concentration following MDMA may result from effects of MDMA on dopamine re‐uptake, monoamine oxidase and 5‐HT release rather than an ‘amphetamine‐like’ action on dopamine release, thus explaining why the drug does not induce degeneration of dopamine nerve endings. British Journal of Pharmacology (1999) 126 , 911–924; doi: 10.1038/sj.bjp.0702373