Mu opioid receptors on vGluT2‐expressing glutamatergic neurons modulate opioid reward
dc.contributor.author | Reeves, Kaitlin C. | |
dc.contributor.author | Kube, Megan J. | |
dc.contributor.author | Grecco, Gregory G. | |
dc.contributor.author | Fritz, Brandon M. | |
dc.contributor.author | Muñoz, Braulio | |
dc.contributor.author | Yin, Fuqin | |
dc.contributor.author | Gao, Yong | |
dc.contributor.author | Haggerty, David L. | |
dc.contributor.author | Hoffman, Hunter J. | |
dc.contributor.author | Atwood, Brady K. | |
dc.contributor.department | Pharmacology and Toxicology, School of Medicine | en_US |
dc.date.accessioned | 2023-01-31T15:34:55Z | |
dc.date.available | 2023-01-31T15:34:55Z | |
dc.date.issued | 2021-05 | |
dc.description.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. | en_US |
dc.eprint.version | Final published version | en_US |
dc.identifier.citation | Reeves KC, Kube MJ, Grecco GG, et al. Mu opioid receptors on vGluT2-expressing glutamatergic neurons modulate opioid reward. Addict Biol. 2021;26(3):e12942. doi:10.1111/adb.12942 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/31063 | |
dc.language.iso | en_US | en_US |
dc.publisher | Wiley | en_US |
dc.relation.isversionof | 10.1111/adb.12942 | en_US |
dc.relation.journal | Addiction Biology | en_US |
dc.rights | Attribution 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.source | PMC | en_US |
dc.subject | Electrophysiology | en_US |
dc.subject | Glutamate | en_US |
dc.subject | Mu opioid receptor | en_US |
dc.subject | Reward | en_US |
dc.subject | Transgenic mice | en_US |
dc.subject | vGluT2 | en_US |
dc.title | Mu opioid receptors on vGluT2‐expressing glutamatergic neurons modulate opioid reward | en_US |
dc.type | Article | en_US |