Acute Negative Allosteric Modulation of M5 Muscarinic Acetylcholine Receptors Inhibits Oxycodone Self-Administration and Cue-Induced Reactivity with no effect on Antinociception
2019
Opioid use disorder(OUD) is a debilitating neuropsychiatric condition characterized by compulsive
opioiduse, dependence, and repeated relapse after periods of abstinence. Given the high risk of developing OUD following prescription
opioiduse, the continued need for
opioid-induced analgesia, and the limitations of current OUD treatments, it is necessary to develop novel, non-
opioid-based treatments for OUD and decrease abuse potential of prescription
opioids. Recent evidence suggests that negative
allosteric modulation(NAM) of the M5
muscarinic acetylcholine receptor(
M5mAChR) may provide an alternative therapeutic approach for the treatment of OUD. Previous studies demonstrated localization of M5 mAChR expression within the mesocorticolimbic reward circuitry and that the selective M5 NAM ML375 attenuates both cocaine and alcohol
self-administrationin rats. In the present study, the effects of ML375 were evaluated in rats self-administering the μ-
opioid agonists
oxycodoneor
remifentanilon a progres...
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