Lack or Inhibition of Dopaminergic Stimulation Induces a Development Increase of Striatal Tyrosine Hydroxylase-Positive Interneurons

Carla Letizia Busceti, Domenico Bucci, Gemma Molinaro, Paola Di Pietro, Luca Zangrandi, Roberto Gradini, Rosario Moratalla, Giuseppe Battaglia, Valeria Bruno, Ferdinando Nicoletti, Francesco Fornai

Research output: Contribution to journalArticle

Abstract

We examined the role of endogenous dopamine (DA) in regulating the number of intrinsic tyrosine hydroxylase-positive (TH+) striatal neurons using mice at postnatal day (PND) 4 to 8, a period that corresponds to the developmental peak in the number of these neurons. We adopted the strategy of depleting endogenous DA by a 2-day treatment with α-methyl-p-tyrosine (αMpT, 150 mg/kg, i.p.). This treatment markedly increased the number of striatal TH+ neurons, assessed by stereological counting, and the increase was highly correlated to the extent of DA loss. Interestingly, TH+ neurons were found closer to the clusters of DA fibers after DA depletion, indicating that the concentration gradient of extracellular DA critically regulates the distribution of striatal TH+ neurons. A single i.p. injection of the D1 receptor antagonist, SCH23390 (0.1 mg/kg), the D2/D3 receptor antagonist, raclopride (0.1 mg/kg), or the D4 receptor antagonist, L-745,870 (5 mg/kg) in mice at PND4 also increased the number of TH+ neurons after 4 days. Treatment with the D1-like receptor agonist SKF38393 (10 mg/kg) or with the D2-like receptor agonist, quinpirole (1 mg/kg) did not change the number of TH+ neurons. At least the effects of SCH23390 were prevented by a combined treatment with SKF38393. Immunohistochemical analysis indicated that striatal TH+ neurons expressed D2 and D4 receptors, but not D1 receptors. Moreover, treatment with the α4β2 receptor antagonist dihydro-β-erythroidine (DHβE) (3.2 mg/kg) also increased the number of TH+ neurons. The evidence that DHβE mimicked the action of SCH23390 in increasing the number of TH+ neurons supports the hypothesis that activation of D1 receptors controls the number of striatal TH+ neurons by enhancing the release of acetylcholine. These data demonstrate for the first time that endogenous DA negatively regulates the number of striatal TH+ neurons by direct and indirect mechanisms mediated by multiple DA receptor subtypes.

Original languageEnglish
Article numbere44025
JournalPLoS One
Volume7
Issue number9
DOIs
Publication statusPublished - Sep 18 2012

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tyrosine 3-monooxygenase
Corpus Striatum
interneurons
Tyrosine 3-Monooxygenase
Interneurons
Neurons
neurons
dopamine
Dopamine
receptors
antagonists
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
agonists
3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3-b)pyridine
Raclopride
Quinpirole
Therapeutics
mice
Dopamine Receptors
acetylcholine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lack or Inhibition of Dopaminergic Stimulation Induces a Development Increase of Striatal Tyrosine Hydroxylase-Positive Interneurons. / Busceti, Carla Letizia; Bucci, Domenico; Molinaro, Gemma; Di Pietro, Paola; Zangrandi, Luca; Gradini, Roberto; Moratalla, Rosario; Battaglia, Giuseppe; Bruno, Valeria; Nicoletti, Ferdinando; Fornai, Francesco.

In: PLoS One, Vol. 7, No. 9, e44025, 18.09.2012.

Research output: Contribution to journalArticle

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AU - Di Pietro, Paola

AU - Zangrandi, Luca

AU - Gradini, Roberto

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