Reserpine pretreatment prevents increases in extracellular striatal dopamine following L-DOPA administration in rats with nigrostriatal denervation

The influence of L-DOPA and reserpine on extracellular dopamine (DA) levels in the striatum of intact and dopaminergic denervated rats was studied usi ng 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 rat s. In rats with 6-hydroxydopamine-induced lesion of the nigrostriatal dopam inergic system, basal levels of extracellular DA were low but markedly incr eased by L-DOPA (50 mg/kg i.p.). In 6-hydroxydopamine-lesioned rats, pretre atment with reserpine (5 mg/kg s.c.) diminished L-DOPA (50 mg/kg i.p.)-indu ced increases in extracellular DA levels to 16% of those obtained in denerv ated animals not pretreated with reserpine (p < 0.01). These results sugges t that in the intact striatum, extracellular DA stems mainly from vesicular storage sites and that in the striatum with dopaminergic denervation, a la rge part of the L-DOPA-derived extracellular DA is also derived from a vesi cular pool that is released by an exocytosis mechanism.