UC San Diego

Opioid drugs are powerful analgesics, however rise in overdoses and deaths led to the United States declaring a public health emergency within the last decade. These drugs in particular can be highly addictive, in part because they activate powerful reward centers in the brain. To investigate the mechanisms by which these pathways work, we anatomically characterized mu opioid receptor (MOR) expressing neurons and glutamatergic, vGlut2- expressing neurons that project to the ventral tegmental area, a canonically known reward center in the brain.I found differentiation in vGlut2 and MOR expressing neuronal inputs to the VTA and surrounding structures from anterior regions of the brain. A majority of vGlut2 inputs to the VTA come from the medial regions of prefrontal cortex such as primary cingulate cortex, prelimbic cortex and infralimbic cortex. In contrast, MOR expressing neuron inputs appear spread more throughout the dorsal and lateral parts of the cortex, with the primary and secondary motor cortexes showing the highest quantities of neurons.These results suggest an alternative to previous ideas that the mPFC is the major source of MOR inputs to VTA and surrounding structures. While we did find MOR labeling in the mPFC, the additional strong presence of MOR expressing neurons in motor and somatosensory cortices raises the question of their importance in opioid effect, and differences between anterior and posterior sections within a given brain region.