PT  - JOURNAL ARTICLE
AU  - Amie L. Severino
AU  - Nitish Mittal
AU  - Joshua K. Hakimian
AU  - Nathanial Velarde
AU  - Ani Minasyan
AU  - Ralph Albert
AU  - Carlos Torres
AU  - Nicole Romaneschi
AU  - Camille Johnston
AU  - Suchi Tiwari
AU  - Alex S. Lee
AU  - Anna M. Taylor
AU  - Claire Gavériaux-Ruff
AU  - Brigitte L. Kieffer
AU  - Christopher J. Evans
AU  - Catherine M. Cahill
AU  - Wendy M. Walwyn
TI  - μ-Opioid Receptors on Distinct Neuronal Populations Mediate Different Aspects of Opioid Reward-Related Behaviors
AID  - 10.1523/ENEURO.0146-20.2020
DP  - 2020 Sep 01
TA  - eneuro
PG  - ENEURO.0146-20.2020
VI  - 7
IP  - 5
4099  - http://www.eneuro.org/content/7/5/ENEURO.0146-20.2020.short
4100  - http://www.eneuro.org/content/7/5/ENEURO.0146-20.2020.full
SO  - eNeuro2020 Sep 01; 7
AB  - μ-Opioid receptors (MORs) are densely expressed in different brain regions known to mediate reward. One such region is the striatum where MORs are densely expressed, yet the role of these MOR populations in modulating reward is relatively unknown. We have begun to address this question by using a series of genetically engineered mice based on the Cre recombinase/loxP system to selectively delete MORs from specific neurons enriched in the striatum: dopamine 1 (D1) receptors, D2 receptors, adenosine 2a (A2a) receptors, and choline acetyltransferase (ChAT). We first determined the effects of each deletion on opioid-induced locomotion, a striatal and dopamine-dependent behavior. We show that MOR deletion from D1 neurons reduced opioid (morphine and oxycodone)-induced hyperlocomotion, whereas deleting MORs from A2a neurons resulted in enhanced opioid-induced locomotion, and deleting MORs from D2 or ChAT neurons had no effect. We also present the effect of each deletion on opioid intravenous self-administration. We first assessed the acquisition of this behavior using remifentanil as the reinforcing opioid and found no effect of genotype. Mice were then transitioned to oxycodone as the reinforcer and maintained here for 9 d. Again, no genotype effect was found. However, when mice underwent 3 d of extinction training, during which the drug was not delivered, but all cues remained as during the maintenance phase, drug-seeking behavior was enhanced when MORs were deleted from A2a or ChAT neurons. These findings show that these selective MOR populations play specific roles in reward-associated behaviors.