Does monoamine oxidase inhibition by pargyline increase extracellular dopamine concentrations in the striatum?

The present study examined the possibility that pargyline-induced stimulation of dopamine neurotransmission in the striatum measured by intracerebral microdialysis may be related to alterations in the function of dopamine nerve terminals in close proximity to the implanted microdialysis probe. Changes in extracellular concentrations of dopamine were determined bilaterally in the striata of awake rats by microdialysis with concentric dialysis probes and by chronoamperometry with electrochemical (stearate-graphite paste) recording electrodes, after inhibition of monoamine oxidase by pargyline and subsequent blockade of dopamine uptake by nomifensine. Pargyline (75 mg/kg, i.p.) increased dopamine overflow by 14 nM from a mean basal value of 9 nM as determined from dialysis probes implanted in the right striatum. Pargyline failed, however, to increase basal concentrations of dopamine measured by electrochemical electrodes implanted alone in the contralateral striatum. In contrast, 3 h following pargyline, administration of nomifensine (10 mg/kg, i.p.) increased extracellular dopamine concentrations to a similar magnitude above baseline levels in both right and left striata (135 and 127 nM, respectively). In a separate group of rats, electrochemical electrodes were implanted in the left striatum with the tip of the 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 concentrations measured at electrodes implanted adjacent to non-perfused dialysis probes to an extent similar to that observed by dialysis alone (25 vs 14 nM, respectively). The present study indicates that pargyline increases dopamine concentrations in the region of striatal tissue immediately adjacent to the shaft of a permanently implanted dialysis probe, but not at the tip of an electrochemical electrode. The former effect appears to reflect an interaction between monoamine oxidase inhibition and the effects elicited by the physical presence of the dialysis probe in tissue.