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
Mi. Colado et al., 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, BR J PHARM, 126(4), 1999, pp. 911-924
1 We investigated whether dopamine plays a role in the neurodegeneration of
5-hydroxytryptamine (5-HT) nerve endings occurring in Dark Agouti rat brai
n after 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') administratio
n.
2 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 atten
uated the neurotoxic loss of 5-HT 7 days later. When the rectal temperature
of MDMA + haloperidol treated rats was kept elevated, this protective effe
ct was marginal.
3 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., pl
us 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 neurode
generation was unaltered. L-DOPA (25 mg kg(-1)) injected before a sub-toxic
dose of MDMA (5 mg kg(-1)) failed to induce neurodegeneration.
4 The MDMA-induced increase in free radical formation in the hippocampus (i
ndicated by increased 2,3- and 2,5-dihydroxybenzoic acid in a microdialysis
probe perfused with salicylic acid) was unaltered by L-DOPA.
5 The neuroprotective drug clomethiazole (50 mg kg(-1) i.p.) did not influe
nce the MDMA-induced increase in extracellular dopamine.
6 These data suggest that previous observations on the protective effect of
haloperidol and potentiating effect of L-DOPA on MDMA-induced neurodegener
ation may have resulted from effects on MDMA-induced hyperthermia.
7 The increased extracellular dopamine concentration following MDMA may res
ult 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 endi
ngs.