The behavioural effects of the serotonin 1A receptor agonist buspirone on reward processing in healthy volunteers: A randomised, placebo-controlled study

Background: The 5-HT_1A receptor is widely expressed throughout the brain and is implicated in reward processing; however, the acute effects of 5-HT_1A receptor agonism on reward and aversive processing in humans remain unclear. Aims: We investigate whether acute 5-HT_1A receptor agonism influences various stages of reward and aversive processing, specifically consummation, motivation and learning. Methods: In a double-blind, placebo-controlled study using a single 20 mg dose of buspirone, a serotonin 5-HT_1A receptor partial agonist, 62 healthy volunteers underwent 3 tasks: a taste task, an effort-expenditure decision task and a probabilistic instrumental learning task (PILT). Results: In healthy volunteers, acute buspirone increases the aversiveness of bitter tastes, non-significantly reduces willingness to exert effort and increases optimal choice during loss trials in the PILT. Conclusions: Speculatively, this could indicate that acute 5-HT_1A agonism may worsen several stages of aversive processing, with minimal effect on reward processing. The study was pre-registered (clinicaltrials.gov, Serotonin-receptor Agonism in Reward Processing, NCT05357547).