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3‐Methoxytyramine Formation Following Monoamine Oxidase Inhibition Is a Poor Index of Dendritic Dopamine Release in the Substantia Nigra
Author(s) -
Elverfors Anders,
Pileblad Erik,
Lagerkvist Sören,
Bergquist Filip,
Jonason Jan,
Nissbrandt Hans
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.69041684.x
Subject(s) - pargyline , reserpine , substantia nigra , dopamine , endocrinology , striatum , chemistry , medicine , amphetamine , monoamine oxidase , dopaminergic , biology , biochemistry , enzyme
This study was undertaken, using microdialysis, to compare the extracellular concentration of 3‐methoxytyramine and dopamine in dialysate from the striatum and substantia nigra, after pargyline (75 mg/kg), after pargyline plus amphetamine (3 mg/kg), and after pargyline plus reserpine (5 mg/kg) administration. Treatment with pargyline alone increased the extracellular dopamine concentration by 70% in the striatum and by 140% in the substantia nigra and induced in both regions a time‐dependent accumulation of 3‐methoxytyramine. The addition of d ‐amphetamine to pargyline increased the extracellular dopamine concentration, compared with pargyline‐treated controls, to the same extent in both the substantia nigra (maximally by 360%) and the striatum (maximally by 400%), but the concomitant increase of 3‐methoxytyramine accumulation in the dialysate was relatively smaller in the substantia nigra compared with the striatum. Reserpine treatment decreased the extracellular dopamine concentration in both regions below the detection level (<10% of basal value). When pargyline was added to reserpine, the striatal extracellular dopamine concentration increased to 50% of pargyline‐treated controls and the striatal 3‐methoxytyramine accumulation was less than in pargyline‐treated controls. However, in the substantia nigra, the addition of pargyline to reserpine resulted in dopamine concentrations as high as after pargyline only and the 3‐methoxytyramine accumulation was not changed compared with pargyline‐treated controls. In summary, our results indicate that dopamine in the substantia nigra is released from reserpine‐sensitive storage sites and that pargyline‐induced 3‐methoxytyramine accumulation is a poor indicator of the local dopamine release. The latter observation may be explained by the fact that the dopamine‐metabolizing enzyme, catechol‐ O ‐methyltransferase, is located inter alia in the dopamine‐containing cell bodies/dendrites in the substantia nigra, in contrast to the situation in the terminals in the striatum where catechol‐ O ‐methyltransferase is located only in nondopaminergic cells.