PCDH-α, -β, and -γ genes are important for many neuronal processes,65–67 but there have been few behavioral studies of the function of specific PCDH-α, -β, and -γ genes. Mice genetically engineered to express low levels of PCDH-α had abnormal fear-related contextual learning and working memory.68 Using RNA-seq to investigate changes in the mouse nucleus accumbens, Eipper-Mains et al. observed dynamic alterations in PCDH-α, -β, and -γ gene mRNA expression in response to cocaine and cocaine withdrawal.69 McGowan et al. observed that the PCDH-α, -β, and -γ gene cluster was differentially regulated by epigenetic mechanisms in the brains of adult rats following a low versus high early-life maternal care paradigm.70 This well established early-life stress paradigm induces later-life differences in hypothalamic-pituitary-adrenal axis function.70, 71 Interestingly. Suderman et al. found that syntenic regions in the human PCDH-α, -β, and -γ gene cluster were differentially regulated in subjects who had experienced severe abuse during childhood, suggesting a potentially conserved mechanism for responding to early life stressors.72 These findings are concordant with the important role of stress regulation and stress response pathways in nicotine
