Acute and long-term effects of a single dose of MDMA on aggression in Dark Agouti rats

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.

Dissociation of the Neurochemical and Behavioral Toxicology of MDMA (‘Ecstasy’) by Citalopram

“…However, the same studies showed that aggressive mood was elevated during the mid-week period following a weekend of Ecstasy use, a phenomenon that could be related to MDMA-induced depletion of 5-HT (Krakowski, 2003;Miczek et al, 2002). In accordance with the human literature, rats given relatively low doses of MDMA showed increased social interaction and decreased aggressive behavior while the drug is still 'on board' (Morley and McGregor, 2000), whereas 5-HT-depleting doses of MDMA produced later increases in aggressiveness in the social interaction test (Ando et al, 2006), though not in the resident-intruder paradigm (Kirilly et al, 2005). When the social interaction test was carried out in the present study, many of the control (SAL/SAL) rats fought when confronted with an unfamiliar male, whereas the animals in the SAL/MDMA group unexpectedly showed significantly less of this behavior.…”

The novelty-seeking phenotype modulates the long-lasting effects of adolescent MDMA exposure

“…Although several reports have associated MDMA and aggressive behavior [64], a single administration of MDMA in rats was shown not to affect aggression after 3 weeks [65], although chronic intermittent administration of MDMA during adolescence reduced social behavior and aggression in adult mice [24]. In line with the present results, Wallinga et al [64] reported an increase in aggression 23 days after chronic MDMA treatment only in low aggressive and not in medium or high aggressive rats.…”

Consequences of concurrent and simultaneous amphetamine-type stimulant and alcohol use among young adults: hazardous drinking, antisocial behaviour, and contact with police

“…This is consistent with the existing evidence indicating that acute ecstasy intoxication may reduce aggression (Curran et al, 2004;Kirilly et al, 2006;Machalova et al, 2012). My findings build on previous research by indicating that even when combined with alcohol ecstasy still does not appear to be associated with aggression.…”

“…Preclinical studies have shown MDMA to cause a dose-dependent reduction in aggression (Kirilly et al, 2006;Machalova, Slais, Vrskova, & Sulcova, 2012). Reductions in selfreported aggression during ecstasy intoxication have also been reported in human studies (Curran, Rees, Hoare, Hoshi, & Bond, 2004).…”

“…Poly-drug use is common among methamphetamine users, with users consuming a range of other licit and illicit substances including alcohol (as discussed above), cannabis, ecstasy, and cocaine (Degenhardt & Topp, 2003;Herbeck et al, 2013 Preclinical studies have shown MDMA to cause a dose-dependent reduction in aggression (Kirilly et al, 2006;Machalova et al, 2012). Reductions in self-reported aggression during ecstasy intoxication have also been reported in human studies (Curran et al, 2004).…”