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The Role of Acid-Sensing Ion Channel 1A (ASIC1A) in the Behavioral and Synaptic Effects of Oxycodone and Other Opioids

Summary

This study examines how a specific type of brain channel called ASIC1A affects how the brain responds to opioid drugs like oxycodone and morphine. Researchers found that mice without this channel showed stronger attraction to opioid-paired locations and had unusual changes in brain connections related to opioid use. The findings suggest that targeting ASIC1A could potentially be a new way to treat opioid addiction by reducing the brain’s sensitivity to these drugs.

Background

Opioid use disorder is a major public health challenge with over 100,000 overdose deaths annually in the United States. Opioid-seeking behaviors depend on glutamatergic plasticity in the nucleus accumbens core, and dendritic spine morphology and AMPAR/NMDAR ratios are critical for substance use disorders. ASIC1A channels have been implicated in drug-seeking behaviors for cocaine and morphine, but their role in oxycodone responses has not been fully elucidated.

Objective

This study investigated whether acid-sensing ion channel 1A (ASIC1A) influences behavioral and synaptic effects of opioids, including oxycodone, morphine, and heroin. The researchers tested ASIC1A disruption on opioid-seeking behavior, dendritic spine morphology, and glutamatergic synaptic transmission in the nucleus accumbens.

Results

ASIC1A disruption increased behavioral responses to acute opioid administration and opioid-seeking behavior in conditioned place preference, with the nucleus accumbens identified as a key site of action. Oxycodone withdrawal reduced spine volume but not density in both genotypes. ASIC1A knockout mice exhibited paradoxical decreased AMPAR/NMDAR ratios following opioid withdrawal compared to increased ratios in wild-type mice, and a single oxycodone dose was sufficient to produce this effect.

Conclusion

ASIC1A plays an important role in behavioral and synaptic responses to opioids, with effects distinct from cocaine. The paradoxical AMPAR/NMDAR ratio changes in ASIC1A knockout mice may underlie their elevated behavioral sensitivity to opioids. ASIC1A may constitute a potential therapeutic target for developing novel therapies for opioid use disorder.
  • Published in:International Journal of Molecular Sciences,
  • Study Type:Experimental Animal Study,
  • Source: PMID: 39519136, DOI: 10.3390/ijms252111584
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