Neonatal 6-OHDA lesions upregulate adult expression of tyrosine hydroxylase mRNA.

We explored the consequences of postnatal day 1 (P1) intrastriatal 6-hydroxydopamine (6-OHDA) lesions on the developing mesostriatal dopamine system by performing in situ hybridization histochemistry for tyrosine hydroxylase (TH) in the substantia nigra-ventral tegmental area (SN-VTA) complex of neonatally-lesioned and non-lesioned animals at P90. There were significant reductions in the expression of TH mRNA from both the rostral and caudal levels of the lateral and medial SNc of 6-OHDA treated animals. The VTA was preferentially spared from the neurotoxic effects of 6-OHDA and showed elevated levels of TH mRNA in the caudal VTA compared with controls. This heterogeneous pattern of TH mRNA expression suggests that early intrastriatal 6-OHDA lesions selectively damage certain DA systems and affect the development of other systems.