Our research focuses on studying the circuit of neurons that project from the dorsal raphe nucleus (DRN) to the ventral tegmental area (VTA). This circuit is important because anatomical studies in rodents have noted the DRN as the densest source of innervation to VTA dopamine neurons, yet the functional role of this circuit is poorly understood. The DRN is the major source of ascending brain serotonin, and it has been presumed that the DRN-VTA circuit is serotonergic. We have found that optogenetic stimulation of DRN serotonin neurons had a weak ability to reinforce instrumental behavior in mice, compared to stimulation of VTA dopamine or DRN non-serotonin populations. These results are in accordance with our experiments using standard behavioral pharmacological analysis of the serotonin- and dopamine- releasing drugs fenfluramine and amphetamine. Using a wide range of doses, we found that fenfluramine failed to produce conditioned place preference using procedures in which amphetamine did so. Similarly, mice self-administered for intravenous injections of amphetamine to a higher degree than mice with access to fenfluramine. Anatomical analysis of non-serotonergic DRN neurons revealed that their primary projection targets are the ventral tegmental area and substantia nigra compacta. Further analysis of these neurons will explore their role in reward behavior.
