Cornichon Family Homolog 3 (CNIH3)
A 2016 genome-wide association study (GWAS) by Nelson et al. identified single nucleotide polymorphisms (SNPs) in cornichon family homolog 3 (CNIH3) to be strongly associated with reduced risk of developing opioid use disorder (OUD) after prior exposure to opioid drugs (Mol Psychiatry, 2016). CNIH3 is an AMPA receptor (AMPAR) auxiliary protein which is highly expressed in the hippocampus, a key region for memory acquisition and retrieval.
Sex Differences
Through the utilization of a range of mouse models with diverse Cnih3 expression profiles, we identified a unique interaction between sex and CNIH3-mediated effects on spatial memory and memory-associated mechanisms in the hippocampus. In these studies, we found that Cnih3 knockdown, knockout, and overexpression only affected memory and hippocampal function in female animals. Upon revisiting the original data included in the human GWAS, we found that the protective haplotypes of the CNIH3 SNPs were significantly stronger in predicting OUD resistance in women than in men.
Current Projects
We are currently conducting studies to determine whether CNIH3 modulates opioid-associated learning and memory in a sex-specific manner in mouse models.
Written by Hannah Frye.