The Systemic Administration of the Histamine H 1 Receptor Antagonist/Inverse Agonist Chlorpheniramine to Pregnant Rats Impairs the Development of Nigro-Striatal Dopaminergic Neurons

• Published in: Frontiers in neuroscience Vol. 13; p. 360
• Main Authors: Márquez-Valadez, Berenice, Aquino-Miranda, Guillermo, Quintero-Romero, Mijail-Oliver, Papacostas-Quintanilla, Helena, Bueno-Nava, Antonio, López-Rubalcava, Carolina, Díaz, Néstor Fabián, Arias-Montaño, José-Antonio, Molina-Hernández, Anayansi
• Format: Journal Article
• Language: English
• Published: Switzerland 16.04.2019
• Subjects: substantia nigra pars compacta development; histamine; H1 receptor; chlorpheniramine; dopaminergic neurons; motor activity
• ISSN: 1662-4548; 1662-453X
• DOI: 10.3389/fnins.2019.00360

The dopaminergic and histaminergic systems are the first to appear during the development of the nervous system. Through the activation of H receptors (H Rs), histamine increases neurogenesis of the cortical deep layers, while reducing the dopaminergic phenotype (cells immunoreactive to tyrosine hydroxylase, TH ) in embryo ventral mesencephalon. Although the function of histamine in neuronal differentiation has been studied, the role of H Rs in neurogenesis has not been addressed. For this purpose, the H R antagonist/inverse agonist chlorpheniramine was systemically administered (5 mg/kg, i.p.) to pregnant Wistar rats (gestational days 12-14, E12-14), and control and experimental embryos (E14 and E16) and pups (21-day-old) were evaluated for changes in nigro-striatal development. Western blot and immunohistochemistry determinations showed a significant increase in the dopaminergic markers' TH and PITX3 in embryos from chlorpheniramine-treated rats at E16. Unexpectedly, 21-day-old pups from the chlorpheniramine-treated group, showed a significant reduction in TH immunoreactivity in the substantia nigra and dorsal striatum. Furthermore, striatal dopamine content, evoked [ H]-dopamine release and methamphetamine-stimulated motor activity were significantly lower compared to the control group. These results indicate that H R blockade at E14-E16 favors the differentiation of dopaminergic neurons, but hampers their migration, leading to a decrease in dopaminergic innervation of the striatum in post-natal life.