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Inhibition of MAO-B protects against MDMA-induced neurotoxicity in the striatum

J E Sprague1, D E Nichols

  • 1Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907, USA.

Psychopharmacology
|April 1, 1995
PubMed

Insights

Monoamine oxidase B (MAO-B) inhibitors, L-deprenyl and MDL-72974, protected against 3,4-methylenedioxymethamphetamine (MDMA)-induced neurotoxicity in rats. These findings highlight MAO-B

Area of Science:

  • Neuroscience
  • Pharmacology
  • Toxicology

Background:

  • 3,4-Methylenedioxymethamphetamine (MDMA) can cause neurotoxicity.
  • Monoamine oxidase B (MAO-B) is an enzyme implicated in neurotransmitter metabolism.

Purpose of the Study:

  • To investigate the role of MAO-B in MDMA-induced serotonergic neurotoxicity.
  • To determine if MAO-B inhibitors can mitigate MDMA's toxic effects on serotonin neurons.

Main Methods:

  • Rats were administered MDMA alone or in combination with MAO-B inhibitors (L-deprenyl, MDL-72974).
  • Serotonergic neurotoxicity was assessed by measuring 5-HT uptake sites (Bmax for [3H]paroxetine binding) and levels of 5-HT and 5-HIAA in the striatum.

Main Results:

  • MDMA administration significantly reduced 5-HT uptake sites and levels of 5-HT and 5-HIAA in the striatum.
  • Co-administration of L-deprenyl or MDL-72974 attenuated the MDMA-induced decrease in these serotonergic markers.

Conclusions:

  • MAO-B plays a significant role in the neurotoxic effects of MDMA in the rat striatum.
  • Inhibiting MAO-B may offer a protective strategy against MDMA-induced serotonergic neurotoxicity.

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