Acute and long-term effects of a single dose of MDMA on aggression in Dark Agouti rats
The International Journal of Neuropsychopharmacology – August 01, 2005
Source: OpenAlex
Summary
MDMA significantly impacts brain function, leading to notable changes in behavior. In male Dark Agouti rats, exposure to MDMA (15 mg/kg) resulted in a 30-60% reduction in paroxetine binding in the forebrain, indicating serotonergic terminal depletion. Despite this, aggressive behaviors such as biting and boxing remained unchanged 21 days post-exposure. Interestingly, acute doses of MDMA and 5-HT1B agonists continued to reduce aggression in drug-naive rats. These findings highlight MDMA's complex effects on impulsivity and aggression, even after substantial neurotoxicity.
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.