Journal article
The Role of Acid-Sensing Ion Channel 1A (ASIC1A) in the Behavioral and Synaptic Effects of Oxycodone and Other Opioids
International journal of molecular sciences, Vol.25(21), 11584
10/29/2024
DOI: 10.3390/ijms252111584
PMCID: PMC11545886
PMID: 39519136
Abstract
Opioid-seeking behaviors depend on glutamatergic plasticity in the nucleus accumbens core (NAcc). Here we investigated whether the behavioral and synaptic effects of opioids are influenced by acid-sensing ion channel 1A (ASIC1A). We tested the effects of ASIC1A on responses to several opioids and found that Asic1a−/− mice had elevated behavioral responses to acute opioid administration as well as opioid seeking behavior in conditioned place preference (CPP). Region-restricted restoration of ASIC1A in NAcc was sufficient to reduce opioid CPP, suggesting NAcc is an important site of action. We next tested the effects of oxycodone withdrawal on dendritic spines in NAcc. We found effects of oxycodone and ASIC1A that contrasted with changes previously described following cocaine withdrawal. Finally, we examined α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated and N-methyl-D-aspartic acid (NMDA) receptor-mediated synaptic currents in NAcc. Oxycodone withdrawal, like morphine withdrawal, increased the AMPAR/NMDAR ratio in Asic1a+/+ mice, whereas oxycodone withdrawal reduced the AMPAR/NMDAR ratio in Asic1a−/− mice. A single dose of oxycodone was sufficient to induce this paradoxical effect in Asic1a−/− mice, suggesting an increased sensitivity to oxycodone. We conclude that ASIC1A plays an important role in the behavioral and synaptic effects of opioids and may constitute a potential future target for developing novel therapies.
Details
- Title: Subtitle
- The Role of Acid-Sensing Ion Channel 1A (ASIC1A) in the Behavioral and Synaptic Effects of Oxycodone and Other Opioids
- Creators
- Margaret J. Fuller - University of IowaNoah R. R. Andrys - University of IowaSubhash C. Gupta - University of IowaAli Ghobbeh - University of IowaCollin J. Kreple - University of Wisconsin–MadisonRong Fan - University of IowaRebecca J. Taugher-Hebl - University of IowaJason J. Radley - University of IowaRyan T. Lalumiere - University of IowaJohn A. Wemmie - University of Iowa
- Resource Type
- Journal article
- Publication Details
- International journal of molecular sciences, Vol.25(21), 11584
- DOI
- 10.3390/ijms252111584
- PMID
- 39519136
- PMCID
- PMC11545886
- NLM abbreviation
- Int J Mol Sci
- ISSN
- 1422-0067
- eISSN
- 1422-0067
- Publisher
- MDPI
- Grant note
- National Institute on Drug AbuseDepartment of Veterans Affairs: IO1BX004440 Roy J. Carver Charitable TrustNational Institute of General Medical Sciences: 3T32GM139776 University of Iowa Medical Scientist Training Program
J.A.W. was supported by the National Institute on Drug Abuse (R01DA052953, 5R01DA037216), Department of Veterans Affairs (Merit Award, IO1BX004440), and Roy J. Carver Charitable Trust. M.J.F. was supported by the National Institute of General Medical Sciences (3T32GM139776) through the University of Iowa Medical Scientist Training Program and by the University of Utah psychiatry residency program Research Track.
- Language
- English
- Date published
- 10/29/2024
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neurosurgery
- Record Identifier
- 9984740060002771
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