Reserpine Pretreatment Prevents Increases in Extracellular Striatal Dopamine Following L-DOPA Administration in Rats with Nigrostriatal Denervation

Authors


  • Abbreviations used: DA, dopamine; L-DOPA, L-3,4-dihydroxyphenylalanine; DOPAC, 3,4-dihydroxyphenylacetic acid; HVA, homovanillic acid; 6-OHDA, 6-hydroxydopamine.

Address correspondence and reprint requests to Dr. K. Kannari at Third Department of Medicine, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8216, Japan. E-mail: kkanhki@umin.ac.jp

Abstract

Abstract: The influence of L-DOPA and reserpine on extracellular dopamine (DA) levels in the striatum of intact and dopaminergic denervated rats was studied using the brain microdialysis technique. In intact rats, reserpine (5 mg/kg s.c.) reduced extracellular DA levels to 4% of basal values. L-DOPA (50 mg/kg i.p.) had no effect on extracellular DA levels in reserpine-pretreated rats. In rats with 6-hydroxydopamine-induced lesion of the nigrostriatal dopaminergic system, basal levels of extracellular DA were low but markedly increased by L-DOPA (50 mg/kg i.p.). In 6-hydroxydopamine-lesioned rats, pretreatment with reserpine (5 mg/kg s.c.) diminished L-DOPA (50 mg/kg i.p.)-induced increases in extracellular DA levels to 16% of those obtained in denervated animals not pretreated with reserpine (p < 0.01). These results suggest that in the intact striatum, extracellular DA stems mainly from vesicular storage sites and that in the striatum with dopaminergic denervation, a large part of the L-DOPA-derived extracellular DA is also derived from a vesicular pool that is released by an exocytosis mechanism.

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