{"doi":"10.1111/adb.12942","title":"Mu opioid receptors on vGluT2‐expressing glutamatergic neurons modulate opioid reward","abstract":"The role of Mu opioid receptor (MOR)-mediated regulation of GABA transmission in opioid reward is well established. Much less is known about MOR-mediated regulation of glutamate transmission in the brain and how this relates to drug reward. We previously found that MORs inhibit glutamate transmission at synapses that express the Type 2 vesicular glutamate transporter (vGluT2). We created a transgenic mouse that lacks MORs in vGluT2-expressing neurons (MORflox-vGluT2cre) to demonstrate that MORs on the vGluT2 neurons themselves mediate this synaptic inhibition. We then explored the role of MORs in vGluT2-expressing neurons in opioid-related behaviors. In tests of conditioned place preference, MORflox-vGluT2cre mice did not acquire place preference for a low dose of the opioid, oxycodone, but displayed conditioned place aversion at a higher dose, whereas control mice displayed preference for both doses. In an oral consumption assessment, these mice consumed less oxycodone and had reduced preference for oxycodone compared with controls. MORflox-vGluT2cre mice also failed to show oxycodone-induced locomotor stimulation. These mice displayed baseline withdrawal-like responses following the development of oxycodone dependence that were not seen in littermate controls. In addition, withdrawal-like responses in these mice did not increase following treatment with the opioid antagonist, naloxone. However, other MOR-mediated behaviors were unaffected, including oxycodone-induced analgesia. These data reveal that MOR-mediated regulation of glutamate transmission is a critical component of opioid reward.","journal":"Addiction Biology","year":2020,"id":94874,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":472562,"name":"Megan J. Kube","orcid":null,"position":1,"is_corresponding":false},{"id":471961,"name":"Gregory G. Grecco","orcid":"0000-0002-0700-8633","position":2,"is_corresponding":false},{"id":471962,"name":"Brandon M. Fritz","orcid":"0000-0001-5856-0527","position":3,"is_corresponding":false},{"id":469453,"name":"Braulio Muñoz","orcid":"0000-0003-4442-975X","position":4,"is_corresponding":false},{"id":472563,"name":"Fuqin Yin","orcid":null,"position":5,"is_corresponding":false},{"id":211006,"name":"Yong Gao","orcid":null,"position":6,"is_corresponding":false},{"id":471963,"name":"David L. Haggerty","orcid":"0000-0002-1455-2557","position":7,"is_corresponding":false},{"id":472564,"name":"Hunter Hoffman","orcid":null,"position":8,"is_corresponding":false},{"id":285573,"name":"Brady K. Atwood","orcid":"0000-0002-7441-2724","position":9,"is_corresponding":false},{"id":471960,"name":"Kaitlin C. Reeves","orcid":"0000-0003-3284-5246","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-18T22:33:00.770265Z","pmid":"32686251","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}