μ-Opioid Receptors on Distinct Neuronal Populations Mediate Different Aspects of Opioid Reward-Related Behaviors.

Titleμ-Opioid Receptors on Distinct Neuronal Populations Mediate Different Aspects of Opioid Reward-Related Behaviors.
Publication TypeJournal Article
Year of Publication2020
AuthorsSeverino AL, Mittal N, Hakimian JK, Velarde N, Minasyan A, Albert R, Torres C, Romaneschi N, Johnston C, Tiwari S, Lee AS, Taylor AM, Gaveriaux-Ruff C, Kieffer BL, Evans CJ, Cahill CM, Walwyn WM
JournaleNeuro
Volume7
Issue5
Date Published2020 Sep/Oct
ISSN2373-2822
Abstract

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.

DOI10.1523/ENEURO.0146-20.2020
Alternate JournaleNeuro
PubMed ID32859725
PubMed Central IDPMC7508564