Direct serotonin release in humans shapes decision computations within aversive environments

Abstract

The role of serotonin in human behaviour is critically informed by approaches which allow in vivo modification of synaptic serotonin. However, characterising the effects of increased serotonin signalling in human models of behaviour is challenging given the limitations of available experimental probes (e.g., SSRIs). Here we use a now accessible approach to directly increase synaptic serotonin in humans - a selective serotonin releasing agent - and examine its influence on domains of behaviour historically considered core functions of serotonin. Computational techniques including reinforcement learning and drift diffusion modelling were fit to observed behaviour. Reinforcement learning models revealed that increased synaptic serotonin reduced sensitivity specifically for outcomes in aversive but not appetitive contexts. Furthermore, increasing synaptic serotonin enhanced behavioural inhibition, and shifted bias towards impulse control during exposure to aversive emotional probes. These effects were seen in the context of overall improvements in memory for neutral verbal information. Our findings highlight the direct effects of increased synaptic serotonin on human behaviour, underlining its critical role in guiding decision-making within aversive and neutral contexts, and offering broad implications for longstanding theories of central serotonin function.