Mu opioid receptors on vGluT2-expressing glutamatergic neurons modulate opioid reward.
Mu opioid receptor
electrophysiology
glutamate
reward
transgenic mice
vGluT2
Journal
Addiction biology
ISSN: 1369-1600
Titre abrégé: Addict Biol
Pays: United States
ID NLM: 9604935
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
06
07
2020
received:
11
04
2020
accepted:
07
07
2020
pubmed:
21
7
2020
medline:
3
11
2021
entrez:
21
7
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32686251
doi: 10.1111/adb.12942
pmc: PMC7854952
mid: NIHMS1623985
doi:
Substances chimiques
Receptors, Opioid, mu
0
Slc17a6 protein, mouse
0
Vesicular Glutamate Transport Protein 2
0
Oxycodone
CD35PMG570
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12942Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR002529
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA027214
Pays : United States
Organisme : NIAAA NIH HHS
ID : T32 AA007462
Pays : United States
Organisme : NIAAA NIH HHS
ID : F32 AA026488
Pays : United States
Informations de copyright
© 2020 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.
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