Ethanol Reversal of Oxycodone Tolerance in Dorsal Root Ganglia Neurons

Molecular Pharmacology
Joanna C JacobHamid I Akbarali

Abstract

Oxycodone is a semisynthetic opioid compound that is widely prescribed, used, and abused today, and has a well-established role in shaping the current opioid epidemic. Previously, we have shown that tolerance develops to the antinociceptive and respiratory depressive effects of oxycodone in mice, and that a moderate dose of acute ethanol or a protein kinase C (PKC) inhibitor reversed that tolerance. To investigate further if tolerance was occurring through neuronal mechanisms, our aims for this study were to assess the effects of acute and prolonged oxycodone in isolated dorsal root ganglia (DRG) neurons and to determine if this tolerance was reversed by either ethanol or a PKC inhibitor. We found that an acute exposure to 3 μM oxycodone reduced neuronal excitability, as measured by increased threshold potentials and reduced action potential amplitude, without eliciting measurable changes in resting membrane potential. Exposure to 10 μM oxycodone for 18-24 hours prevented oxycodone's effect on neuronal excitability, indicative of tolerance development. The development of opioid tolerance was mitigated in DRG neurons from β-arrestin 2 knockout mice. Oxycodone tolerance was reversed in isolated DRG neurons by the acute applicatio...Continue Reading

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Citations

Apr 9, 2021·Peptides·Richard J Bodnar
Nov 12, 2020·Canadian Journal of Physiology and Pharmacology·Cheng-Wei LuSu-Jane Wang

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