EFFLUX OF DOPAMINE FROM THE SYNAPTIC CLEFT IN THE NUCLEUS-ACCUMBENS OF THE RAT-BRAIN

Synaptic release of dopamine in the nucleus accumbens of the intact ra t brain elicited by a single electrical impulse applied to ascending d opaminergic fibers results in extracellular concentrations sufficient to bind the known dopamine receptors. The dopamine concentration obser ved after four rapid, sequential pulses is exactly four times greater and is unaffected by pharmacological antagonism of dopamine uptake and receptor sites at supramaximal concentrations. Thus, dopamine efflux from the synaptic cleft is not restricted by binding to intrasynaptic proteins on the time scale of the measurements (50-100 msec). The extr acellular concentration, as a result of a single stimulus pulse, is 0. 25 mu M and is rapidly removed by extrasynaptic uptake. This maximal, transient concentration of dopamine is 60 times higher than steady-sta te concentrations reported previously using dialysis techniques, illus trating that dopamine extracellular concentrations are spatially and t emporally heterogenous. In contrast to ACh transmission at the neuromu scular junction, the dopamine synapse in the telencephalon is designed for the effective efflux of dopamine from the synaptic cleft to the e xtrasynaptic compartment during neurotransmission.