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Chunk #23 — Discussion

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ELK1 transcription factor linked to dysregulated striatal mu opioid receptor signaling network and OPRM1 polymorphism in human heroin abusers.
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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 hours following heroin self-administration is generally associated with enhanced stress response that involves the activation of the hypothalamic-pituitary axis and glucocorticoid receptor system.(59, 60) Interestingly, glucocorticoid receptor stimulation increases pELK1 (61), suggesting that increased pELK1 24 hours after heroin may be a result of withdrawal-induced stress. Such time course changes could also have distinct functional relevance depending on the cellular localization of pELK1 at these periods since ELK1 localization in dendritic, cytoplasmic and nuclear compartments has significant implications regarding its effects on dendritic sprouting and transcriptional regulation. (62–64)