C/EBPβ couples dopamine signalling to substance P precursor gene expression in striatal neurones

Abstract

Dopamine-induced changes in striatal gene expression are thought to play an important role in drug addiction and compulsive behaviour. In this study we report that dopamine induces the expression of the transcription factor CCAAT/Enhancer Binding Protein β (C/EBP)-β in primary cultures of striatal neurones. We identifed the preprotachykinin-A (PPT-A) gene coding for substance P and neurokinin-A as a potential target gene of C/EBPβ. We demonstrated that C/EBPβ physically interacts with an element of the PPT-A promoter, thereby facilitating substance P precursor gene transcription. The regulation of PPT-A gene by C/EBPβ could subserve many important physiological processes involving substance P, such as nociception, neurogenic inflammation and addiction. Given that substance P is known to increase dopamine signalling in the striatum and, in turn, dopamine increases substance P expression in medium spiny neurones, our results implicate C/EBPβ in a positive feedback loop, changes of which might contribute to the development of drug addiction. © 2006 The Authors.