UPTAKE OF DOPAMINE RELEASED BY IMPULSE FLOW IN THE RAT MESOLIMBIC ANDSTRIATAL SYSTEMS IN-VIVO

The release of dopamine in the striatum, nucleus accumbens, and olfact ory tubercle of anesthetized rats was evoked by electrical stimulation of the mesolimbic dopaminergic pathway (four pulses at 15 Hz or four pulses at 200 Hz). Carbon fiber electrodes were implanted in these reg ions to monitor evoked dopamine overflow by continuous amperometry. Th e kinetics of dopamine elimination were estimated by measuring the tim e to 50% decay of the dopamine oxidation current after stimulation cea sed. This time ranged from 64 ms in the striatum to 113 ms in the nucl eus accumbens, inhibition of dopamine uptake by nomifensine (2-20 mg/k g), GBR 12909 (20 mg/kg), cocaine (20 mg/kg), mazindol (10 mg/kg), or bupropion (25 mg/kg) enhanced this decay time by up to +602%, Uptake i nhibition also produced an increase in the maximal amplitude of dopami ne overflow evoked by four pulses at 15 Hz. This latter effect was lar ger in the striatum (+420%) than in mesolimbic areas (+140%). These re sults show in vivo that these uptake inhibitors actually slow the clea rance of dopamine released by action potentials and suggest that dopam inergic transmission is both prolonged and potentiated strongly by the se drugs, in particular in the striatum.