DOES MONOAMINE-OXIDASE INHIBITION BY PARGYLINE INCREASE EXTRACELLULARDOPAMINE CONCENTRATIONS IN THE STRIATUM

The present study examined the possibility that pargyline-induced stim ulation of dopamine neurotransmission in the striatum measured by intr acerebral microdialysis may be related to alterations in the function of dopamine nerve terminals in close proximity to the implanted microd ialysis probe. Changes in extracellular concentrations of dopamine wer e determined bilaterally in the striata of awake rats by microdialysis with concentric dialysis probes and by chronoamperometry with electro chemical (stearate-graphite paste) recording electrodes, after inhibit ion of monoamine oxidase by pargyline and subsequent blockade of dopam ine uptake by nomifensine. Pargyline (75 mg/kg, i.p.) increased dopami ne overflow by 14 nM from a mean basal value of 9 nM as determined fro m dialysis probes implanted in the right striatum. Pargyline failed, h owever, to increase basal concentrations of dopamine measured by elect rochemical electrodes implanted alone in the contralateral striatum. I n contrast, 3 h following pargyline, administration of nomifensine (10 mg/kg, i.p.) increased extracellular dopamine concentrations to a sim ilar magnitude above baseline levels in both right and left striata (1 35 and 127 nM, respectively). In a separate group of rats, electrochem ical electrodes were implanted in the left striatum with the tip of th e electrode placed directly adjacent to the lumen of a dialysis probe. In contrast to pargyline's inability to increase basal extracellular dopamine measured at individually implanted electrochemical electrodes in the striatum, pargyline administration increased dopamine concentr ations measured at electrodes implanted adjacent to non-perfused dialy sis probes to an extent similar to that observed by dialysis alone (25 vs 14 nM, respectively). The present study indicates that pargyline i ncreases dopamine concentrations in the region of striatal tissue imme diately adjacent to the shaft of a permanently implanted dialysis prob e, but not at the tip of an electrochemical electrode. The former effe ct appears to reflect an interaction between monoamine oxidase inhibit ion and the effects elicited by the physical presence of the dialysis probe in tissue. Copyright (C) 1996 IBRO.