Abstract
Our aim was to study the specific role of the postsynaptic D1 receptors on dopaminergic response and analyze the metabolized dopamine (DA) in the rat striatum. We used male Wistar rats to evaluate the effects of different doses of a D1 agonist (SKF-38393) and a D1 antagonist (SCH-23390), and their co-administration. The levels of DA and L-3, 4-dihydroxyphenylacetic acid (DOPAC) were measured using high performance liquid chromatography. The systemic injection of SKF-38393 alone at 1, 5 and 10 mg/kg did not alter the DA and DOPAC levels or the DOPAC/DA ratio. In contrast, injection of SCH-23390 alone at 0.25, 0.5 and 1 mg/kg significantly increased the DA and DOPAC levels, as well as the DOPAC/DA ratio, compared with the respective control groups. The co-administration of SCH-23390+SKF-38393 did not alter the DA or DOPAC levels, but it did significantly inhibit the SCH-23390-induced increase of the DA and DOPAC levels. The SCH-23390+SKF-38393 and the SCH-23390-only groups showed an increase in the DOPAC/DA ratio. The co-administration of SCH-23390+PARGYLINE significantly decreased the DOPAC levels and the DOPAC/DA ratio compared with the control and SCH-23390 groups. Taken together, our results showed that selective inhibition with SCH-23390 produced an increase in metabolized DA via striatal monoamine oxidase. These findings also contribute to the understanding of the role of postsynaptic D1 receptors in the long-loop negative feedback system in the rat striatum.
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Acknowledgments
This study is from the first author as a member of the Doctorate Program in Biological Science at the Universidad Autónoma Metropolitana Iztapalapa-Xochimilco. Bueno-Nava was supported by the scholarship No. 47133 from CONACYT in Mexico. The technical assistance of J.L. Cortés-Altamirano and I. Villafaña-Rivera is greatly appreciated. The authors wish to thank Dra. Ivonne M. Heuze de Icasa for his support with the experimental animals.
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The authors declare that there are no conflicts of interest.
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Bueno-Nava, A., Gonzalez-Pina, R., Alfaro-Rodriguez, A. et al. The Selective Inhibition of the D1 Dopamine Receptor Results in an Increase of Metabolized Dopamine in the Rat Striatum. Neurochem Res 37, 1783–1789 (2012). https://doi.org/10.1007/s11064-012-0790-5
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DOI: https://doi.org/10.1007/s11064-012-0790-5