Serotonergic and nonserotonergic participation in reward circuitry
September 25, 2014
Defining Reward Circuitry
Previous research has shown that the Dorsal Raphe Nucleus (DRN) plays a paradoxical role in reward. Although it contains the brain’s largest group of serotonin-producing neurons and projects to regions controlling reward, including the Ventral Tegmental Area (VTA), drugs that boost serotonergic activity in this region (such as antidepressants) have low abuse potential. Yet, electrically stimulating the DRN strongly reinforces conditioned instrumental behaviors (e.g. bar press). To better clarify the role of the DRN in reward and reinforcement learning, researchers at NIDA’s Intramural Research Program used a range of pharmacological and optogenetic methods to test the reinforcing effects of stimulating serotonergic and nonserotonergic neurons in the DRN of transgenic mice. They found that reinforcement was produced through stimulation of nonserotonergic DRN cells and that these make up the bulk of the neurons projecting to the VTA (contrary to earlier views). In addition, they found that GABA-ergic and dopaminergic neurons are not the cells mediating these rewarding effects. From this they inferred that glutamatergic neurons in the DRN-VTA projection are the cells responsible; this was supported by the observation of strong glutamatergic currents produced by stimulating this pathway. This study helps to better define the brain’s reward circuitry and opens up new avenues of investigation related to the neurobiology of addiction.