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Stoichiometry of Tyrosine Hydroxylase Phosphorylation in the Nigrostriatal and Mesolimbic Systems In Vivo
Author(s) -
Salvatore Michael F.,
GarciaEspana Antonio,
Goldstein Menek,
Deutch Ariel Y.,
Haycock John W.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0750225.x
Subject(s) - ventral tegmental area , raclopride , haloperidol , tyrosine hydroxylase , nucleus accumbens , chemistry , striatum , endocrinology , medicine , substantia nigra , dopamine , biology , dopaminergic
; Electrical stimulation of the medial forebrain bundle increases 32 P incorporation into striatal tyrosine hydroxylase (TH) at Ser 19 , Ser 31 , and Ser 40 . In the present studies, the effects of acute haloperidol and related drugs on sitespecific TH phosphorylation stoichiometry (PS) in the nigrostriatal and mesolimbic systems were determined by quantitative blot immunolabeling using phosphorylation statespecific antibodies. The striatum (Str), substantia nigra (SN), nucleus accumbens (NAc), and ventral tegmental area (VTA) from Sprague‐Dawley rats were harvested 30‐40 min after a single injection of either vehicle, haloperidol (2 mg/kg), raclopride (2 mg/kg), clozapine (30 mg/kg), or SCH23390 (0.5 mg/kg). In vehicle‐injected control rats, Ser 19 PS was 1.5‐ to 2.5‐fold lower in Str and NAc than in SN and VTA, Ser 31 PS was two‐to fourfold higher in Str and NAc than in SN and VTA, and Ser 40 PS was similar between the terminal field and cell body regions. After haloperidol, Ser 40 PS increased twofold in Str and NAc, whereas a smaller increase in SN and VTA was observed. The effects of haloperidol on Ser 19 PS were similar to those on Ser 40 in each region ; however, haloperidol treatment increased Ser 31 PS at least 1.6‐fold in all regions. The effects of raclopride on TH PS were comparable to those of haloperidol, whereas clozapine treatment increased TH PS at all sites in all regions. By contrast, the effects of SCH23390 on TH PS were relatively small and restricted to the NAc. The stoichiometries of site‐specific TH phosphorylation in vivo are presented for the first time. The nigrostriatal and mesolimbic systems have common features of TH PS, distinguished by differences in TH PS between the terminal field and cell body regions and by dissimilar increases in TH PS in the terminal field and cell body regions after acute haloperidol.