TY - JOUR
T1 - The neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine on serotonin, dopamine, and GABA-ergic terminals
T2 - An in-vitro autoradiographic study in rats
AU - Armstrong, Brian D.
AU - Noguchi, Kevin K.
N1 - Funding Information:
We would like to thank Dr. Gaylord Ellison for his generosity in support of this study. Research sponsored by NIDA Grant DA 07344.
PY - 2004/12
Y1 - 2004/12
N2 - Damage to serotonin (5-HT) terminals following doses of 3,4-methylenedioxymethamphetamine (MDMA) is well documented, and this toxicity is thought to be related to dopamine release that is potentiated by the 5-HT2A/2C agonist effects of the drug [Neurotoxicology 19 (3) (1998) 427]. Although MDMA and methamphetamine (METH) have some similar dopaminergic activities, they differ in their 5-HT agonistic properties. It is reasoned that the study of the resultant toxicity following equimolar doses of MDMA and METH on both dopamine and 5-HT terminals should offer a comparison of the ability of these drugs to induce neurotoxicity. In order to measure the toxic effects to the brain, rats were given equimolar doses of MDMA (40 mg/kg/day) and METH (32 mg/kg/day) in subcutaneously implanted osmotic minipumps for a period of 5 days, and in-vitro autoradiography using [3H]-paroxetine, [ 3H]-mazindol, [3H]-methylspiperone, and [ 3H]-flunitrazepam, was performed on brain sections. The results showed that METH was more toxic to 5-HT terminals than MDMA in forebrain regions, including the anterior cingulate, caudate nucleus, nucleus accumbens, and septum. METH was also more toxic than MDMA to dopamine terminals in the habenula, and posterior retrosplenial cortex. Therefore, we find that METH was more toxic to 5-HT and dopamine terminals in specific brain regions in both pre and post-synaptic sites following continuous equimolar dosing.
AB - Damage to serotonin (5-HT) terminals following doses of 3,4-methylenedioxymethamphetamine (MDMA) is well documented, and this toxicity is thought to be related to dopamine release that is potentiated by the 5-HT2A/2C agonist effects of the drug [Neurotoxicology 19 (3) (1998) 427]. Although MDMA and methamphetamine (METH) have some similar dopaminergic activities, they differ in their 5-HT agonistic properties. It is reasoned that the study of the resultant toxicity following equimolar doses of MDMA and METH on both dopamine and 5-HT terminals should offer a comparison of the ability of these drugs to induce neurotoxicity. In order to measure the toxic effects to the brain, rats were given equimolar doses of MDMA (40 mg/kg/day) and METH (32 mg/kg/day) in subcutaneously implanted osmotic minipumps for a period of 5 days, and in-vitro autoradiography using [3H]-paroxetine, [ 3H]-mazindol, [3H]-methylspiperone, and [ 3H]-flunitrazepam, was performed on brain sections. The results showed that METH was more toxic to 5-HT terminals than MDMA in forebrain regions, including the anterior cingulate, caudate nucleus, nucleus accumbens, and septum. METH was also more toxic than MDMA to dopamine terminals in the habenula, and posterior retrosplenial cortex. Therefore, we find that METH was more toxic to 5-HT and dopamine terminals in specific brain regions in both pre and post-synaptic sites following continuous equimolar dosing.
KW - Autoradiography
KW - Crystal METH
KW - Ecstasy
KW - MDMA
KW - Neurotoxicity
UR - https://www.scopus.com/pages/publications/5044234467
U2 - 10.1016/j.neuro.2004.06.003
DO - 10.1016/j.neuro.2004.06.003
M3 - Article
C2 - 15474609
AN - SCOPUS:5044234467
SN - 0161-813X
VL - 25
SP - 905
EP - 914
JO - NeuroToxicology
JF - NeuroToxicology
IS - 6
ER -