The neurocircuitry of incubation of relapse to opioid seeking

The main challenge in opioid addiction treatment is high relapse rates.

To date, preclinical studies of opioid relapse are limited and have used animal models in which the abstinence period prior to relapse testing is forced.

In contrast, abstinence in humans is often self-imposed and drug-seeking episodes during abstinence typically involve a conflict situation where the drug user chooses between the desire to experience the drug’s rewarding effects and the adverse consequences of seeking the drug.

I have developed a rat model to study opioid relapse after voluntary abstinence due to adverse concequenses of drug seeking and showed a role of ventral subiculum (vSub) and dorsomedial striatum (DMS) in relapse to oxycodone.

I propose to use this new rat model to determine the role of molecular mechanisms within activated vSub neurons, and within inputs to vSub or DMS activated during oxycodone relapse.

First, I will use fluorescently activated cell sorting plus RNA-sequencing, and viral approaches to identify molecular mechanisms within activated vSub neurons that promots oxycodone relapse (Aim 1).

Next, I will combine brain imaging, immunohistochemistry, and retrograde tracing methods to identify neuronal projections to vSub or DMS that are activated during oxycodone relapse (Aim 2).

Finally, I will use a chemogenetic-based projection-specific inhibition method to determine the causal role of the identified neuronal projections to vSub or DMS in oxycodone relapse (Aim 3).