Related Experiment Video
Updated: Aug 16, 2026
Social Defeat Stress Model for Adolescent C57BL/6 Male and Female Mice
Published on: March 15, 2024
Acute and long-term effects of a single dose of MDMA on aggression in Dark Agouti rats
Eszter Kirilly1, Anita Benko, Linda Ferrington
1Laboratory of Neurochemistry and Experimental Medicine and Department of Vascular Neurology, Semmelweis University, National Institute of Psychiatry and Neurology, Budapest, Hungary.
Abstract:
MDMA causes selective depletion of serotonergic terminals in experimental animals and the consequent decrease in synaptic 5-HT may, inter alia, increase impulsivity. To study the effects of MDMA upon brain function, the behaviour of male Dark Agouti rats exposed to MDMA (15 mg/kg i.p.), two 5-HT1B agonists (CGS-12066A and CP-94,253, both 5 mg/kg i.p.) or saline were investigated in the resident-intruder test. Studies were performed in drug-naive rats and also in rats exposed to MDMA (15 mg/kg i.p.) 21 d earlier. In parallel experiments the functional neuroanatomy of MDMA effects were assessed using 2-deoxyglucose imaging of local cerebral metabolic rate of glucose utilization (LCMRGlu) and neurotoxicity was assessed by measuring [3H]paroxetine binding. There was no significant difference in aggressive behaviour (biting, boxing, wrestling and their latencies) between drug-naive rats and rats previously exposed to MDMA 21 d earlier, despite reduced social behaviour, decreased LCMRGlu in several brain areas involved in aggression, and reductions in paroxetine binding by 30-60% in the forebrain. CGS-12066A, CP-94,253 and acute MDMA produced marked decreases in aggressive behaviours, especially in biting, boxing and kicking found in drug-naive rats. In animals previously exposed to the drug, acute anti-aggressive effects of MDMA were, in general, preserved as were MDMA-induced increases in LCMRGlu. Our studies provide evidence that in the resident-intruder test, where social isolation is a requirement, aggressive behaviour and acute anti-aggressive effects of MDMA and 5-HT1B receptor agonists remain intact 3 wk after a single dose of the drug despite significant damage to the serotonergic system.
Insights
MDMA
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- MDMA (3,4-methylenedioxymethamphetamine) depletes serotonin (5-HT) in animals, potentially increasing impulsivity.
- The 5-HT1B receptor plays a role in regulating behavior.
Purpose of the Study:
- To investigate the long-term effects of MDMA on aggressive behavior and brain function in rats.
- To assess the impact of MDMA-induced serotonergic damage on behavioral responses to MDMA and 5-HT1B agonists.
Main Methods:
- Rats were tested in the resident-intruder test after acute MDMA or saline administration.
- Some rats received a single MDMA dose 21 days prior to testing.
- Brain activity was measured using 2-deoxyglucose imaging (LCMRGlu) and neurotoxicity was assessed via [3H]paroxetine binding.
Main Results:
- MDMA, 5-HT1B agonists, and acute MDMA significantly reduced aggressive behaviors in drug-naive rats.
- Rats previously exposed to MDMA showed preserved anti-aggressive effects of acute MDMA and maintained MDMA-induced increases in LCMRGlu.
- Despite significant serotonergic damage (30-60% reduction in paroxetine binding), aggressive behavior and acute anti-aggressive effects remained intact 3 weeks after a single MDMA dose.
Conclusions:
- Aggressive behavior and the anti-aggressive effects of MDMA and 5-HT1B agonists persist three weeks after a single MDMA dose, despite substantial serotonergic system damage.
- These findings suggest that the serotonergic system's role in aggression may be more complex than previously thought, with potential compensatory mechanisms at play.
