EFFECTS OF CGP-28014 ON THE IN-VIVO RELEASE AND METABOLISM OF DOPAMINE IN THE RAT STRIATUM ASSESSED BY BRAIN MICRODIALYSIS

The effects on rat striatal dopamine (DA) metabolism of systemic and l ocal administration of CGP 28014, an inhibitor of catechol-O-methyl-tr ansferase (COMT), were studied by in vivo microdialysis. CGP 28014 (30 mg/kg i.p.) significantly reduced the levels of homovanillic acid (HV A), but did not modify DA and 3,4-dihydroxyphenylacetic acid (DOPAC). The intrastriatal administration (via the microdialysis probe) of 5, 7 .5, 10, and 20 mM of CGP 28014 elicited a concentration-dependent, sev eral-fold increase in extracellular DA but did not alter the levels of HVA and DOPAC. Thus, the effects of CGP 28014 observed after i.p. inj ection (decrease in HVA levels) are different from those measured afte r intrastriatal administration (increase in DA release). Therefore, th e inhibition of COMT is likely to be due to the action of a metabolite of CGP 28014 formed in the periphery and not in the brain.