Haloperidol activates tyrosine hydroxylase gene-expression in the rat substantia nigra, pars reticulata

The cellular distribution of tyrosine hydroxylase (TH) and TH mRNA in the rat substantia nigra (SN) was investigated using immunohistochemistry (IMHC) and non-radioactive in situ hybridization histochemistry (ISH), respectively. Number and density of both TH immunoreactive and TH cRNA labeled cells were increased in the pars reticulata of the substantia nigra (SNr) 8 h after single administration of a dopamine antagonist haloperidol. At the same time number and density of TH positive cells remained unchanged in a ventro-medial, dorso-medial or lateral part of the pars compacta (SNc) and in the pars lateralis (SNl) of the substantia nigra. A D2 receptor-specific agonist, quinpirole, was without effect on either ISH or IMHC in any of these areas, including the SNr. These results reveal the existence of a population of TH-negative neurons in the SNr, in which TH gene-expression can be activated through a dopamine receptor-mediated mechanism, leading to detectable levels of both TH and TH mRNA. Furthermore they suggest that TH gene-expression in these neurons normally is inhibited by dopamine released from somata and dendrites in the SNr.