Role of the Noradrenergic System in the Regulation of Learning Dynamics: Evaluation of the Effect of a Low-dose Selective Noradrenaline Reuptake Inhibitor (NOISYXETINE)

Condition(s) studied

Investigational drug(s) / intervention(s)

Atomoxetine: One single capsule of atomoxetine 40 mg given at one visit according to the sequence randomly allocated. Placebo of atomoxetine will be administered at the other visit for the participant (according to the sequence randomly allocated)

Placebo: One single capsule of placebo given at one visit according to the sequence randomly allocated.

Study summary

Administration of low-dose selective noradrenaline reuptake inhibitor (sNRI) (e.g. atomoxetine) to healthy subjects is a validated model of increasing cortical noradrenaline levels which, combined with computational modelling of behaviour, allows fine-grained analysis of the impact on learning processes of noradrenaline's fluctuations in the human cortex.

The study goal is to characterize the modifications of certain cognitive processes and associated brain circuits under low-dose sNRI using validated computational learning models. The study will be interested in how subjects will modify their learning under the effect of the drug across two separate investigations; one utilizing in a stable evidence accumulation task and one utilising a changing evidence accumulation task. This approach will help to better understand the link between noradrenaline and accumulation of evidence in healthy subjects, and indirectly in some neuropsychiatric pathologies.

The study is a single centre, double-blinded, randomized, placebo-controlled, cross-over study involving evaluable healthy adults separated in 2 cohorts: A for participants having the stable task and B for those having the changing one. Participants will then be randomized in a 1:1 ratio to one of the following treatment sequences:

* Atomoxetine 40 mg - Placebo (Subgroups A1 or B1);
* Placebo - Atomoxetine 40 mg (Subgroups A2 or B2).

Eligibility

Primary outcome measure(s)

• Apparent Learning rate — From Visit 1 (Day 0) to Visit 2 (Day 7)
  Paired difference in the apparent learning rates (in both environmental contexts: stable task and changing task), between the sNRI (atomoxetine) and control (placebo) conditions. Apparent learning rate will be calculate with the following formula: αt=(vt- vt-(1) )/(xt- vt-1) according to Foucault and Meyniel (Foucault C, Meyniel F (2024) Two Determinants of Dynamic Adaptive Learning for Magnitudes and Probabilities. Open Mind : Discov Cogn Sci 8:615-638) The learning rate measures the amount of update of the learned value (from vt-(1 to vt) induced by the observation xt in proportion to its deviation from the previously learned value.

Trial sites (1)

More Centre Hospitalier St Anne trials in France