OPRM1 and opiate dependence: Repeated exposure to exogenous opioids can lead to receptor desensitization and tolerance that reduces the number of functional receptors.51,52 Opioid-induced changes in MOR signaling within the HP circuit have not been assessed, but MORs in the HP circuit can contribute to the manifestation of behaviors linked to opioid dependence and withdrawal.21,36 Future work must therefore investigate how chronic exposure to exogenous opioids changes the HP circuit, and it will be important to assess how MOR signaling changes within distinct cellular and subcellular compartments.