title: Haloperidol activates tyrosine hydroxylase gene-expression in the rat substantia nigra, pars reticulata.
abstract: 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.
authors.affiliation: Laboratory of Neurochemistry, National Institute for Physiological Sciences, Okazaki, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Stork
authors.forename: T
authors.initials: T
authors.lastname: Hashimoto
authors.forename: K
authors.initials: K
authors.lastname: Obata
mesh_terms: D000818:Animals; D048588:Benzoxazines; D015259:Dopamine Agents / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004789:Enzyme Activation / Q000187:drug effects; D004873:Ergolines / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D010078:Oxazines; D019257:Quinpirole; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology*; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
chemical_list: D048588:Benzoxazines; D015259:Dopamine Agents; D065127:Dopamine D2 Receptor Antagonists; D004873:Ergolines; D010078:Oxazines; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; C028911:cresyl violet; D014446:Tyrosine 3-Monooxygenase; D006220:Haloperidol