Effects of MDMA Injections on the Behavior of Socially-Housed Long-Tailed Macaques (Macaca fascicularis)

Abstract

3,4-methylenedioxy-N-methyl amphetamine (MDMA) is one of the few known molecules to increase human and rodent prosocial behaviors. However, this effect has never been assessed on the social behavior of non-human primates. In our study, we subcutaneously injected three different doses of MDMA (1.0, 1.5 or 2.0mg/kg) to a group of three, socially housed, young male long-tailed macaques. More than 200 hours of behavioral data were recorded, during 68 behavioral sessions, by an automatic color-based video device that tracked the 3D positions of each animal and of a toy. This data was then categorized into 5 exclusive behaviors (resting, locomotion, foraging, social contact and object play). In addition, received and given social grooming was manually scored. Results show several significant dose-dependent behavioral effects. At 1.5mg/kg only, MDMA induces a significant increase in social grooming behavior, thus confirming the prosocial effect of MDMA in macaques. Additionally, at 1.5 and 2.0 mg/kg MDMA injection substantially decreases foraging behavior, which is consistent with the known anorexigenic effect of this compound. Furthermore, at 2.0 mg/kg MDMA injection induces an increase in locomotor behavior, which is also in accordance with its known stimulant property. Interestingly, MDMA injected at 1.0mg/kg increases the rate of object play, which might be interpreted as a decrease of the inhibition to manipulate a unique object in presence of others, or, as an increase of the intrinsic motivation to manipulate this object. Together, our results support the effectiveness of MDMA to study the complex neurobiology of primates’ social behaviors.

3,4-Methylenedioxymethamphetamine Increases Affiliative Behaviors in Squirrel Monkeys in a Serotonin 2A Receptor-Dependent Manner

“…Studies have shown that MDMA increases feelings of sociability in humans and increases social interaction in rodents (Kamilar-Britt and Bedi, 2015). The only study to examine the social effects of MDMA in nonhuman primates also found that MDMA increases social grooming in longtailed macaques (Ballesta et al, 2016). In concordance with this research, the present experiments found that MDMA significantly increases huddling and affiliative calls in squirrel monkeys.…”

“…Further, squirrel monkeys have a pharmacokinetic profile for MDMA similar to humans (Mueller et al, 2009), providing considerable translational relevance, given the concern that different pharmacokinetic processing can alter the effects of MDMA (Green et al, 2012). Despite these advantages, only one study has examined the social effects of MDMA in nonhuman primates (Ballesta et al, 2016), and no studies have used nonhuman primates to analyze the mechanisms underlying the social effects of MDMA. Here behavioral and vocal changes were examined following administration of MDMA, its enantiomers, or methamphetamine.…”

Development of social systems neuroscience using macaques

“… 174 ) Furthermore, the assessment of social behavioral changes induced by drug injections has also been started under group settings. 175 ) Further refinements of experimental procedures, for both behavioral and neural data collection, are expected with technological advancements. The effective combination of the group-based experimental strategy, which is suitable for screening individual social behavioral traits, and the two-monkey laboratory testing strategy, which is suitable for in-depth electrophysiological investigations, will provide a fruitful platform for future social neuroscience research using macaques.…”

A Systematic Review of the MDMA Model to Address Social Impairment in Autism

“…Since dosage effects are different between species, we will observe each animal model in turn. Four studies tested the behavioural effects of MDMA on monkeys [ 98 - 101 ]. They found that chronic administration of 1.5 mg/kg s.c. [ 98 ], or singular dose of 0.03-3 mg/kg i.m.…”

“…Four studies tested the behavioural effects of MDMA on monkeys [ 98 - 101 ]. They found that chronic administration of 1.5 mg/kg s.c. [ 98 ], or singular dose of 0.03-3 mg/kg i.m. [ 100 ] increased prosocial behaviour.…”