Another enzyme showing association with acute stimulant drug responses is casein kinase 1 epsilon (CSNK1E). CSNK1E encodes an enzyme that phosphorylates dopamine and cAMP-regulated phosphoprotein (DAARP-32; PPP1R1B), a second messenger that integrates dopaminergic and glutamatergic signaling (Greengard 2001). We have previously reported that a quantitative trait locus (QTL) for methamphetamine sensitivity co-maps with an expression QTL for Csnk1e in mice, suggesting that the latter might cause the former (Palmer et al. 2005). Furthermore, pharmacological inhibition of Csnk1e blocks the locomotor response to methamphetamine in mice (Bryant et al. 2009) and rats (unpublished data). Mice with a null allele for Csnk1e exhibit paradoxically higher response to methamphetamine (unpublished data). We have also investigated the effects of SNPs in CSNK1E on subjective amphetamine response in humans (Veenstra-VanderWeele et al. 2006). The C allele of rs135745, which is located in the 3′-UTR of the gene, was associated with the response to amphetamine at 10 mg (but not 20 mg) as measured by the DEQ Feel Drug and ARCI Euphoria scales. Interestingly, other SNPs in CSNK1E have been associated with both heroin addiction in
