Cornichon Homolog-3 (Cnih3) deletion impairs spatial memory, operant learning, and fentanyl self-administration...

Area of Science:

• Neuroscience
• Genetics
• Pharmacology

Background:

• Opioid misuse is a significant public health issue, with new synthetic opioids emerging.
• Genome-wide association studies (GWAS) are identifying potential genetic targets for opioid use disorder (OUD).
• Cornichon Homolog-3 (CNIH3) is a potential target identified through genetic studies, but its role in opioid use is unknown.

Purpose of the Study:

• To investigate the behavioral role of CNIH3 in opioid use and related behaviors.
• To characterize the effects of CNIH3 deletion on various behavioral domains in mice.

Main Methods:

• Utilized mice with CNIH3 deletion.
• Assessed a battery of behaviors including well-being, affect, memory, learning, and opioid self-administration.
• Employed principal component analysis for unbiased behavioral dimension analysis.

Main Results:

• CNIH3 deletion moderately impaired spatial memory and operant learning (sucrose self-administration).
• CNIH3 deletion delayed fentanyl intravenous self-administration acquisition in females.
• CNIH3 deletion reduced fentanyl intake during self-administration in both sexes.

Conclusions:

• CNIH3 plays a role in modulating spatial memory, learning, and opioid intake.
• CNIH3 is identified as a behaviorally relevant protein in opioid-related plasticity.
• These findings contribute to understanding the genetic underpinnings of OUD and potential therapeutic targets.