Limited insights are available regarding the role of ELK1 in neuropsychiatric disorders, but its molecular regulation has been described. Phosphorylation of ELK1 by ERK1/2 is critical for its translocation into the nucleus where it can exert effects on chromatin and gene expression.(58) The fact that total ELK1 was increased in the putamen of human heroin abusers concomitant with a decrease in pELK1 levels suggested that less ELK1 is trafficked to the nucleus and transcription of ELK1 target genes may be decreased. Indeed, total ELK1 was positively correlated to heroin at 1 hour after heroin intake in animals that directly self-administered heroin, similar to human abusers, and pELK1 levels were negatively correlated with heroin use, irrespective of the time of death following the last drug intake. These findings emphasize an important contribution of the history of repeated heroin use on ELK1 phosphorylation. Interestingly, the absolute levels of pELK1 were elevated 24 hours after heroin use, indicative of an acute withdrawal effect or a potential compensation to counter reduction of pELK1 as a consequence of repeated heroin use. Acute opiate withdrawal 24
