IPAC integrates rewarding and environmental memory during the acquisition of morphine CPP

The association between rewarding and drug-related memory is a leading factor for the formation of addiction, yet the neural circuits underlying the association remain unclear. Here, we showed that the interstitial nucleus of the posterior limb of the anterior commissure (IPAC) integrated rewarding and environmental memory information by two different receiving projections from ventral tegmental area (VTA) and nucleus accumbens shell region (NAcSh) to mediate the acquisition of morphine conditioned place preference (CPP). A projection from the VTA GABAergic neurons (VTA GABA ) to the IPAC lateral region GABAergic neurons (IPACL GABA ) mediated the effect of morphine rewarding, whereas the pathway from NAcSh dopamine receptor 1–expressing neurons (NAcSh D1 ) to the IPAC medial region GABAergic neurons (IPACM GABA ) was involved in the acquisition of environmental memory. These findings demonstrated that the distinct IPAC circuits VTA GABA → IPACL GABA and NAcSh D1R → IPACM GABA were attributable to the rewarding and environmental memory during the acquisition of morphine CPP, respectively, and provided the circuit-based potential targets for preventing and treating opioid addiction.