D1 Antagonists and D2 Agonists Have Opposite Effects on the Metabolism of Dopamine in the Rat Striatum

The striatum is known to possess high levels of D-1-like and D-2-like receptors (D(1)Rs and D(2)Rs, respectively). We have previously shown that selective inhibition of D(1)Rs increases the dopaminergic metabolic response and proposed that this effect is associated with the concomitant activation of postsynaptic D(2)Rs by endogenous dopamine (DA). Here, we examined whether activation of D(2)Rs modulates the metabolism and synthesis of DA in the striatum. We used male Wistar rats to evaluate the effects of the systemic administration of a D2R agonist (bromocriptine), a D1R antagonist (SCH-23390), and the co-administration of these compounds with pargyline on the inhibition of monoamine oxidase. DA and l-3,4-dihidroxyphenylacetic acid (DOPAC) levels and 3,4-dihydroxy-l-phenylalanine (l-DOPA) content were measured using high performance liquid chromatography. The systemic administration of SCH-23390 alone, at 0.25, 0.5, 1 or 2 mg/kg, significantly (P < 0.05) increased DOPAC levels and the DOPAC/DA ratio. At 2, 4 and 8 mg/kg, the administration of bromocriptine alone significantly (P < 0.05) decreased DOPAC levels, l-DOPA content and the DOPAC/DA ratio, whereas at 2 mg/kg, it decreased DA levels. In both groups, co-administration of either SCH-23390 or bromocriptine with pargyline decreased DOPAC levels and the DOPAC/DA ratio by approximately 70 % compared to the levels observed in the control groups. In conclusion, administration of the D2R agonist bromocriptine decreased dopaminergic synthesis and metabolism in the striatum; in contrast, administration of the D1R antagonist SCH-23390 induced the opposite effects.