Constraint of Motivation and Value by Limbic Opioidergic Systems

Abstract

The mesolimbic pathway connects the ventral tegmental area (VTA) to the nucleus accumbens (NAc) and has been extensively studied for its role in processing rewards, mediating reinforcement learning and promoting motivated behavior. The role of small molecule neurotransmitters such as dopamine (DA), glutamate and GABA has been extensively studied in the mesolimbic pathway within the context of reward and motivation. However, there are many opioid peptide systems that directly modulate neuronal populations within the mesolimbic pathway that have yet to be thoroughly investigated for their contribution to reward behavior. DA neurons in VTA highly express nociceptin opioid peptide receptors (NOPR) that are endogenously activated by the nociceptin ligand. Downstream of VTA DA neurons in NAc, there are two principal spiny projection neuron (SPN) cell types that express either excitatory dopamine receptors (D1R) or inhibitory dopamine receptors (D2R). D1R-SPNs also express and release the endogenous opioid dynorphin, while D2R-SPNs express another critical endogenous opioid, enkephalin. The presented studies investigate how these opioid-expressing neuronal populations are involved in facilitating reward behavior and motivation.