Related Experiment Video

Updated: Jan 27, 2026

Application of a NMDA Receptor Conductance in Rat Midbrain Dopaminergic Neurons Using the Dynamic Clamp Technique
06:42

Application of a NMDA Receptor Conductance in Rat Midbrain Dopaminergic Neurons Using the Dynamic Clamp Technique

Published on: December 21, 2010

12.5K

Increased iNOS and Nitrosative Stress in Dopaminergic Neurons of MDMA-Exposed Rats

Stefania Schiavone1, Margherita Neri2, Angela Bruna Maffione3

  • 1Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli, 20, 71122 Foggia, Italy. stefania.schiavone@unifg.it.

International Journal of Molecular Sciences
|March 16, 2019
PubMed

Insights

3,4-Methylenedioxy-N-methylamphetamine (MDMA) neurotoxicity may stem from inducible nitric oxide synthase (iNOS)-derived nitrosative stress, not reactive oxygen species (ROS) producing NOX enzymes. This highlights specific enzyme roles in MDMA

Area of Science:

  • Neuroscience
  • Toxicology
  • Biochemistry

Background:

  • MDMA neurotoxicity mechanisms are debated, involving reactive oxygen species (ROS), nitric oxide (NO), and reactive nitrogen species (RNS).
  • Sources of ROS, NO, and RNS in the brain contributing to MDMA neurotoxicity remain unclear.
  • Understanding these pathways is crucial for addressing the neurotoxic effects of MDMA abuse.

Purpose of the Study:

  • To investigate alterations in NOX enzymes, NO generators, and oxidative/nitrosative stress markers following MDMA administration in rats.
  • To examine the colocalization of dopamine transporter (DT1) positive cells with neuronal markers and glial cells after MDMA exposure.
  • To determine the specific roles of NOX enzymes versus iNOS in MDMA-induced neurotoxicity.

Main Methods:

  • Rats were administered saline or MDMA and sacrificed at 6, 16, or 24 hours.
  • Immunoreactivity for NOX enzymes (NOX2, NOX1, NOX4), NO generators (iNOS, eNOS, nNOS), 8-hydroxy-2'-deoxyguanosine (8OHdG), and 3-nitrotyrosine (NT) was assessed.
  • Colocalization studies were performed for DT1, neuronal nuclei (NeuN), microglia, astrocytes, and MDMA.

Main Results:

  • MDMA did not alter NOX2, NOX1, or NOX4 expression but significantly enhanced inducible nitric oxide synthase (iNOS) expression.
  • Increased 3-nitrotyrosine (NT) positive cells were observed in MDMA-exposed rats, while 8-hydroxy-2'-deoxyguanosine (8OHdG) levels remained unchanged.
  • MDMA and NT markers colocalized with dopamine transporter (DT1) positive neurons, which were found within NeuN-positive cells, with minimal association with glial cells.

Conclusions:

  • Inducible nitric oxide synthase (iNOS)-derived nitrosative stress, indicated by 3-nitrotyrosine (NT), plays a significant role in MDMA-induced neurotoxicity.
  • Reactive oxygen species (ROS) produced by NOX enzymes do not appear to be the primary drivers of MDMA neurotoxicity.
  • These findings underscore the specific contributions of different enzymatic systems to the neuropathological alterations caused by MDMA abuse.
Keywords:
MDMANADPH oxidasesiNOSnitrosative stressoxidative stress

More Related Videos

Primary Culture of Mouse Dopaminergic Neurons11:58

Primary Culture of Mouse Dopaminergic Neurons

Published on: September 8, 2014

39.2K
Directed Dopaminergic Neuron Differentiation from Human Pluripotent Stem Cells06:40

Directed Dopaminergic Neuron Differentiation from Human Pluripotent Stem Cells

Published on: September 15, 2014

17.2K

Related Concept Videos

Nitrosation of Enols01:19

Nitrosation of Enols

The nitrosation reaction is one of the methods of preparing 1,2-diketones. The enol tautomer of the starting ketone reacts with sodium nitrite in hydrochloric acid, generating the 1,2-diketone after hydrolysis.
9.4K
Increased Body Temperature01:25

Increased Body Temperature

A body temperature above  38°C  (100.4 °F) is known as fever or pyrexia, and a person with fever is termed 'febrile.' Typically, the hypothalamus, a part of the brain that acts as the body's thermostat, regulates body temperature through a thermoregulatory setpoint. It receives signals from cold and warm thermal receptors throughout the body and adjusts the body's temperature accordingly. Fever occurs when this hypothalamic setpoint is altered, usually in...
7.4K
Increased pulse rate01:17

Increased pulse rate

Tachycardia is a condition marked by an abnormally fast or irregular heart rate, surpassing the typical resting rate. In adults, tachycardia is characterized by a pulse rate ranging from 100 to 180 beats per minute. The increased heart rate can result in inadequate blood flow to various body parts, ultimately diminishing the oxygen supply to organs and tissues.
Many factors can elevate the risk of developing tachycardia. These include advanced age, a family history of arrhythmias, and an...
1.2K
Responses to Heat and Cold Stress02:45

Responses to Heat and Cold Stress

Every organism has an optimum temperature range within which healthy growth and physiological functioning can occur. At the ends of this range, there will be a minimum and maximum temperature that interrupt biological processes.
14.7K
Responses to Salt Stress02:02

Responses to Salt Stress

Salt stress—which can be triggered by high salt concentrations in a plant’s environment—can significantly affect plant growth and crop production by influencing photosynthesis and the absorption of water and nutrients.
14.5K
General State of Stress01:21

General State of Stress

The general state of stress within a material can be accurately depicted using a stress tensor. This tensor encapsulates the internal forces distributed within a material subjected to external forces or deformations.
Specifically, consider a tetrahedral element where one face, labeled XYZ, is perpendicular to the line OA, and the remaining faces align with the coordinate axes with point O as the origin. At any point, such as point O, the stress tensor can be used to determine the stress...
643