6-Hydroxydopamine Lesion Prevents Induction of Tyrosine Hydroxylase by Haloperidol in the Rat Substantia Nigra, Pars Reticulata.

Abstract

We investigated the number of tyrosine hydroxylase (TH)-positive neurons in the rat substantia nigra (SN) after unilateral lesion of SN dopamine neurons with intranigral 6-hydroxydopamine (6-OHDA) injection. Non-radioactive in situ hybridization procedure and immunohistochemistry detected much less (<5%) TH-positive neurons in the lesioned SN, compared with the contralateral side. Single administration of a dopamine antagonist haloperidol failed to increase TH labeling on the lesioned side, although it increased that in the contralateral SN pars reticulata (SNr), as in the case of unlesioned animals. These results indicate that 6-OHDA destroyed not only TH-positive SN neurons but also TH-negative but -inducible SNr neurons. It is probable that these "TH inducible" SNr neurons are dopaminergic neurons although they usually do not express TH at detectable levels.