Impact of an early serotonergic lesion by MDMA (Ecstasy) on anxious-like behavior in non-human primates (NHP)

Objective: To investigate the causal impact of an early serotonergic lesion on the expression of anxious-like behavior.

Methods: The serotonergic lesion was performed on NHP by using 3,4-methylenedioxy-N-methamphetamine (MDMA or Ecstasy) and evaluated by PET imaging using the [11C]DASB radioligand. Behavioral assessment was made with an instrumental delay task with positive or negative outcomes and two conditions (choice or imperative). The monkeys were trained to associate conditioned stimuli (CS) with appetitive (marker of motivation; juice) or aversive (marker of anxiety; airpuff) outcome.

Results: We observed decrease of binding of this tracer about 31 % on average in both subcortical and cortical areas. No impact of MDMA was observed for all monkeys in the choice condition of the task. However, for the imperative condition, the performances of the monkeys were rapidly altered after MDMA in aversive single-cue trials. We observed for all monkeys an increase of premature responses and/or non-initiated actions, two behavioral markers of aversive sensibility. These alterations did not persist as the performances of the monkeys returned to baseline around two weeks after MDMA intoxication.

Conclusion: Altogether, these results suggest that the early serotonergic lesion does not alter motivation (no link with apathy) but rather induces an anxious-like behavior, which is revealed by the appearance of a hypersensibility to the aversive outcome.