Selective increase of Nurr1 mRNA expression in mesencephalic dopaminergic neurons of D2 dopamine receptor-deficient mice

The orphan nuclear receptor Nurr1 is critical for the survival of mesenceph alic dopaminergic precursor neurons. Little is known about the mechanisms t hat regulate Nurr1 expression in vivo. Other members of this receptor famil y have been shown to be activated by dopamine. We sought to determine if Nu rr1 expression is also regulated by endogenous dopamine through dopamine re ceptors. Consequently, we investigated the expression of Nurr1 mRNA in gene tically modified mice lacking both functional copies of the D2 dopamine rec eptor gene and in their congenic siblings. Quantitative in situ hybridizati on demonstrated a significant increased expression of Nurr1 mRNA in the sub stantia nigra pars compacta and the ventral tegmental area of D2 dopamine r eceptor -/- mice. No change in Nurr1 expression was detected in other brain regions, such as the habenular nuclei and temporal cortex. Among the cell groups studied, mesencephalic dopaminergic neurons are unique in that they express both Nurr1 and the D2 dopamine receptor, and synthesize dopamine. T hus, it seems plausible that the selective increase in Nurr1 expression obs erved in D2 receptor-deficient mice is the consequence of an impaired dopam ine autoreceptor function. (C) 2000 Elsevier Science B.V. All rights reserv ed.