Effects of a 5-HT 4 receptor antagonist in the caudate nucleus on the performance of macaques in a delayed reward task.

Temporal discounting, in which the recipient of a reward perceives the value of that reward to decrease with delay in its receipt, is associated with impulsivity and psychiatric disorders such as depression. Here, we investigate the role of the serotonin 5-HT ₄ receptor (5-HT ₄ R) in modulating temporal discounting in the macaque dorsal caudate nucleus (dCDh), the neurons of which have been shown to represent temporally discounted value. We first mapped the 5-HT ₄ R distribution in macaque brains using positron emission tomography (PET) imaging and confirmed dense expression of 5-HT ₄ R in the dCDh. We then examined the effects of a specific 5-HT ₄ R antagonist infused into the dCDh. Blockade of 5-HT ₄ R significantly increased error rates in a goal-directed delayed reward task, indicating an increase in the rate of temporal discounting. This increase was specific to the 5-HT ₄ R blockade because saline controls showed no such effect. The results demonstrate that 5-HT ₄ Rs in the dCDh are involved in reward-evaluation processes, particularly in the context of delay discounting, and suggest that serotonergic transmission via 5-HT ₄ R may be a key component in the neural mechanisms underlying impulsive decisions, potentially contributing to depressive symptoms.
(© 2024. The Author(s).)