%0 Journal Article %T Lack or Inhibition of Dopaminergic Stimulation Induces a Development Increase of Striatal Tyrosine Hydroxylase-Positive Interneurons %A Carla Letizia Busceti %A Domenico Bucci %A Gemma Molinaro %A Paola Di Pietro %A Luca Zangrandi %A Roberto Gradini %A Rosario Moratalla %A Giuseppe Battaglia %A Valeria Bruno %A Ferdinando Nicoletti %A Francesco Fornai %J PLOS ONE %D 2012 %I Public Library of Science (PLoS) %R 10.1371/journal.pone.0044025 %X 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 ¦Á-methyl-p-tyrosine (¦ÁMpT, 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 ¦Á4¦Â2 receptor antagonist dihydro-¦Â-erythroidine (DH¦ÂE) (3.2 mg/kg) also increased the number of TH+ neurons. The evidence that DH¦ÂE 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. %U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0044025