The Selective Inhibition of the D^sub 1^ Dopamine Receptor Results in an Increase of Metabolized Dopamine in the Rat Striatum

• Published in: Neurochemical research Vol. 37; no. 8; p. 1783
• Main Authors: Bueno-nava, A, Gonzalez-pina, R, Alfaro-rodriguez, A, Avila-luna, A, Arch-tirado, E, Alonso-spilsbury, M
• Format: Journal Article
• Language: English
• Published: New York Springer Nature B.V 01.08.2012
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-012-0790-5

Our aim was to study the specific role of the postsynaptic D^sub 1^ 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 D^sub 1^ agonist (SKF-38393) and a D^sub 1^ 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 D^sub 1^ receptors in the long-loop negative feedback system in the rat striatum.[PUBLICATION ABSTRACT]