Modulation of dihydroxyphenylacetaldehyde extracellular levels in vivo in the rat strictum after different kinds of pharmacological treatment

We recently identified the direct product of dopamine (DA) by monoamine-oxi dose (MAO) activity, dihydroxyphenylacetaldehyde (DOPALD) in the trans-stri atal dialysate. Based on these findings, in this work, we directly measured the variations in DOPALD levels after various kinds of pharmacological tre atment in rat striatal extracellular fluid. Using both reversible and irrev ersible MAO inhibitors, we found that MAO-A inhibition suppressed, whereas MAO-B inhibition did not modify DOPALD levels in the dialysate. The vesicul ar DA uptake blocker Ro 4-1284 led to an increase in extracellular DA and D OPALD, whereas the increase in extracellular DA obtained after administrati on of the plasma membrane DA uptake blocker GBR-12909 occurred without conc omitant changes in DOPALD extracellular levels. Microinfusions of DA throug h the dialysis probe or systemic administration of L-DOPA increased striata l DOPALD to a greater extent compared with other DA metabolites, both in in tact and in 6-hydroxydopamine (6-OHDA)-lesioned striatum. This study indica tes that the direct product of MAO activity within the rat striatum derives from the activity of the isoenzyme MAO-A. The assay of DOPALD, together wi th DOPAC, represents a reliable tool to measure directly, in freely moving animals, DA oxidative metabolism, As recent studies have shown that microin fusions of exogenous DOPALD might induce cell death, pharmacological modula tion of DOPALD levels might also be relevant for an understanding of the me chanisms involved in DA neurotoxicity. (C) 2000 Elsevier Science B.V. All r ights reserved.