Activation of Dorsal Raphe Serotonergic Neurons Promotes Waiting but Is Not Reinforcing

The central neuromodulator serotonin (5-HT) has been implicated in a wide range of behaviors and affective disorders, but the principles underlying its function remain elusive. One influential line of research has implicated 5-HT in response inhibition and impulse control. Another has suggested a role in affective processing. However, whether and how these effects relate to each other is still unclear. Here, we report that optogenetic activation of 5-HT neurons in the dorsal raphe nucleus (DRN) produces a dose-dependent increase in mice’s ability to withhold premature responding in a task that requires them to wait several seconds for a randomly delayed tone. The 5-HT effect had a rapid onset and was maintained throughout the stimulation period. In addition, movement speed was slowed, but photostimulation did not affect reaction time or time spent at the reward port. Using similar photostimulation protocols in place preference and value-based choice tests, we found no evidence of either appetitive or aversive effects of DRN 5-HT neuron activation. These results provide strong evidence that the efficacy of DRN 5-HT neurons in promoting waiting for delayed reward is independent of appetitive or aversive effects and support the importance of 5-HT in behavioral persistence and impulse control. •Optogenetic activation of serotonin neurons promotes waiting for delayed rewards•The effect of serotonin neuron activation is not general to all motor behaviors•Serotonin neuron activation shows no appetitive or aversive effects Fonseca et al. show that optogenetic activation of serotonergic neurons in the dorsal raphe nucleus prolongs waiting for delayed rewards but has no aversive or appetitive effects in several different behavioral assays. These results establish a link between serotonin and impulse control that is independent of reinforcing effects.