Serotonin modulates learning content-specific neuroplasticity of functional brain networks

Learning-induced neuroplastic changes, further modulated by content and setting, are mirrored in brain functional connectivity. Animal models emphasized the crucial role of serotonin in neuroplasticity particularly for emotional relearning, but comparable studies in humans are scarce. Assessing the translation of learning effects from animals to humans, 99 healthy subjects underwent six weeks of emotional or semantic learning and subsequent relearning and three resting-state acquisitions for functional connectivity estimation. During relearning, subjects received either a daily dose of the selective serotonin reuptake inhibitor escitalopram or placebo. The influence of escitalopram on functional connectivity was connection- and learning content-dependent, with potentiation of decreases during emotional and increases during semantic learning. The directedness of these effects indicates serotonergic modulation of emotional feedback routes. These results demonstrate that escitalopram intake during relearning facilitates content-dependent network adaptations and support the conclusion that enhanced neuroplasticity might be the major underlying mechanism in psychiatric therapies.