The viruses used in this article from BrainVTA are in the table below

Both the ventral tegmental area (VTA) and dorsal raphe nucleus (DRN) are involved in affective control and reward-related behaviors. Moreover, the neuronal activities of the VTA and DRN are modulated by opioids. However, the precise circuits from the VTA to DRN and how opioids modulate these circuits remain unknown. Here, we found that neurons projecting from the VTA to DRN are primarily GABAergic. Rostral VTA (rVTA) GABAergic neurons preferentially innervate DRN GABAergic neurons, thus disinhibiting DRN serotonergic neurons. Optogenetic activation of this circuit induces aversion. In contrast, caudal VTA (cVTA) GABAergic neurons mainly target DRN serotonergic neurons, and activation of this circuit promotes reward. Importantly,μ-opioid receptors (MOPs) are selectively expressed at rVTA/DRN GABAergic synapses, and morphine depresses the synaptic transmission. Chronically elevating the activity of the rVTA/DRN pathway specifically interrupts morphine-induced conditioned place preference. This opioid-modulated inhibitory circuit may yield insights into morphine reward and dependence pathogenesis.

Figure 1. DRN Serotonergic and GABAergic Neurons Received Dense Projections from Caudal and Rostral VTA GABAergic Neurons

The authors investigated the precise connections between the VTA and DRN and the functions of these circuits using rabies virus tracing, electrophysiology, and behavioral assays, identifying distinct pathways that specifically modulate morphine reward without affecting the analgesic effects of morphine.
 
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