Cytochrome P450 mediates dopamine formation in the brain in vivo

Abstract

The cytochrome P450-mediated synthesis of dopamine from tyramine has been shown in vitro. The aim of the present study was to demonstrate the ability of rat cytochrome P450 (CYP) 2D to synthesize dopamine from tyramine in the brain in vivo. We employed two experimental models using reserpinized rats with a blockade of the classical pathway of dopamine synthesis from tyrosine. Model A estimated dopamine production from endogenous tyramine in brain structures in vivo (ex vivo measurement of a tissue dopamine level), while Model B measured extracellular dopamine produced from exogenous tyramine (an in vivo microdialysis). In Model A, quinine (a CYP2D inhibitor) given intraperitoneally caused a significant decrease in dopamine level in the striatum and nucleus accumbens and tended to fall in the substantia nigra and frontal cortex. In Model B, an increase in extracellular dopamine level was observed after tyramine given intrastructurally (the striatum). After joint administration of tyramine and quinine, the amount of the dopamine formed was significantly lower compared to the group receiving tyramine only. The results of the two complementary experimental models indicate that the hydroxylation of tyramine to dopamine may take place in rat brain in vivo, and that CYP2D catalyzes this reaction.