Abstract

Introduction In humans, empathy is expressed through various prosocial behaviours between individuals that may be enhanced after intake of the synthetic entactogen MDMA (3,4-methylenedioxymethamphetamine, "Ecstasy") as the behavioural expression of the so-called entactogenic syndrome. Rodents may also exhibit empathy-like behaviours, such as social interaction and helping behaviour. In this regard, while social interaction has been reported to be enhanced by MDMA, the effects of this drug on helping behaviour remain unexplored. Nevertheless, because helping behaviour is considered as part of the prosocial repertoire, it may be hypothesised that MDMA should enhance it.Methods In the present study, the evaluation of a subtoxic dose range (0.25 mg/kg, 0.5 mg/kg, 1 mg/kg, 5 mg/kg, and 10 mg/kg i.p.) of MDMA on helping behaviour in adult male rats has been conducted using a standardised behavioural setup based on the intrinsic aversion of these animals to water. In addition, as helping behaviour may require a complex interaction between motivational and higher cognitive processes, the neuroplastic effects of MDMA (10 mg/kg i.p.) on cortical and subcortical loci were studied in vivo in anaesthetised rats.Results and discussion Behavioural data indicated that 5 mg/kg and 10 mg/kg of MDMA fully suppressed helping behaviour; 1 mg/kg and 0.5 mg/kg induced partial inhibition only after interchanging roles; and 0.25 mg/kg had no effect. The inhibitions observed at the highest doses (5 mg/kg, and 10 mg/kg) were not reversed after interchanging roles. Electrophysiological data showed that MDMA reinforced long-term depression (LTD) elicited in the nucleus accumbens (NAc) core following stimulation of the dorsal raphe nucleus (DRN). In addition, MDMA increased transcallosal-evoked long-term potentiation (LTP) in the anterior cingulate cortex (ACC) in a serotonin (5-HT)- and oxytocin (OXT)-dependent manner. Taken together, these data support the notion that MDMA disrupts helping behaviour, even though the neuroplastic effects elicited by the drug align with the mechanisms described to promote prosocial/empathic behaviours. The results may suggest a negative modulation of MDMA on neural processes that are essential for the execution of helping behaviour without affecting the willingness to help.