3,4-Methylenedioxy-N-methamphetamine (ecstasy) promotes the survival of fetal dopamine neurons in culture.
Jack W Lipton, Emeline G Tolod, Valerie B Thompson, Lin Pei, Katrina L Paumier, Brian T Terpstra, Kaari A Lynch, Timothy J Collier, Caryl E Sortwell
Neuropharmacology October 2008 DOI: 10.1016/j.neuropharm.2008.06.062 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro cell culture and in vivo animal study Peer reviewed |
|---|---|
| Population | Fetal midbrain dopamine neurons in culture and prenatally MDMA-exposed animals examined on postnatal day 35 |
| Interventions | MDMA methylphenidate |
| Topics | MDMA |
| Key points | MDMA, at concentrations observed in fetal brain, increased dopamine neuron survival in culture without affecting neurite outgrowth, and this effect appeared to be mediated by MDMA's action at the dopamine transporter, since methylphenidate blocked and then restored the effect as its concentration was reduced. Prenatally exposed animals showed increased tyrosine hydroxylase-positive neurons in the substantia nigra but not the ventral tegmental area. |
Abstract
The current study examined whether modest concentrations of MDMA could increase the survival and/or neurite outgrowth of fetal midbrain dopamine (DA) neurons in vitro since increased DA neurite outgrowth has been previously observed in vivo from prenatal exposure. MDMA concentrations in fetal brain were quantified to determine relevant in vivo concentrations to employ in vitro. A dose response study in vitro demonstrated that MDMA, at concentrations observed in vivo, resulted in increased, DA-specific, neuron survival. Higher doses resulted in non-specific neurotoxicity. MDMA application immediately after culture establishment resulted in greater survival than delayed application, however both were superior to control. MDMA significantly increased the expression of the slc6a3 gene (dopamine transporter; DAT) in culture. Co-application of the DAT reuptake inhibitor methylphenidate (MPH) with MDMA attenuated this effect. Progressive reductions in MPH concentrations restored the MDMA-induced survival effect. This suggests that MDMA's action at DAT mediates the survival effect. Neurite density per neuron was unaffected by MDMA in vitro suggesting that MDMA promotes DA neuron survival but not neurite outgrowth in culture. Finally, animals prenatally exposed to MDMA and examined on postnatal day 35 showed an increase in tyrosine hydroxylase-positive (TH+) neurons in the substantia nigra but not in the ventral tegmental area. These data suggest that during development, MDMA can increase the survival of DA neurons through its action at its transporter. Understanding how MDMA increases DA neuron survival may provide insight into normal DA neuron loss during development.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cites 9
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- (±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Studies in Animals Neuropsychobiology 2000
- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
- Lasting Neuropsychiatric Sequelae of (??)Methylenedioxymethamphetamine (???Ecstasy???) in Recreational Users Journal of Clinical Psychopharmacology October 1, 1991
- MDMA administration to pregnant Sprague-Dawley rats results in its passage to the fetal compartment. Neurotoxicology and Teratology 2006
and 4 more in the library