D sub(1) Antagonists and D sub(2) Agonists Have Opposite Effects on the Metabolism of Dopamine in the Rat Striatum

The striatum is known to possess high levels of D sub(1)-like and D sub(2)-like receptors (D sub(1)Rs and D sub(2)Rs, respectively). We have previously shown that selective inhibition of D sub(1)Rs increases the dopaminergic metabolic response and proposed that this effect is associated with the concomitant activation of postsynaptic D sub(2)Rs by endogenous dopamine (DA). Here, we examined whether activation of D sub(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 D sub(2)R agonist (bromocriptine), a D sub(1)R 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 D sub(2)R agonist bromocriptine decreased dopaminergic synthesis and metabolism in the striatum; in contrast, administration of the D sub(1)R antagonist SCH-23390 induced the opposite effects.