BIOCHEMISTRY OF SOMATODENDRITIC DOPAMINE RELEASE IN SUBSTANTIA-NIGRA - AN IN-VIVO COMPARISON WITH STRIATAL DOPAMINE RELEASE

The somatodendritic release of dopamine in substantia nigra previously has been suggested to be nonvesicular in nature and thus to differ fr om the classical, exocytotic release of dopamine described for the dop aminergic nerve terminal in striatum. We have compared the effects of reserpine, a compound that disrupts vesicular sequestration of monoami nes, on the storage and release of dopamine in substantia nigra and st riatum of rats. Reserpine administration (5 mg/kg, i.p.) significantly decreased the tissue level of dopamine in substantia nigra pars retic ulata, substantia nigra pars compacta, and striatum. In these brain ar eas, reserpine-induced reductions in tissue dopamine level occurred wi thin 2 h and persisted at 24 h postdrug. In vivo measurements using mi crodialysis revealed that reserpine administration rapidly decreased t he extracellular dopamine concentration to nondetectable levels in sub stantia nigra as well as in striatum. In both structures, it was obser ved that reserpine treatment significantly attenuated the release of d opamine evoked by a high dose of amphetamine (10 mg/kg, i.p.) given 2 h later. in contrast, dopamine efflux in response to a low dose of amp hetamine (2 mg/kg, i.p.) was not altered by reserpine pretreatment eit her in substantia nigra or in striatum. The present data suggest the e xistence, both at the somatodendritic and at the nerve terminal level, of a vesicular pool of dopamine that is the primary site of transmitt er storage and that can be displaced by high but not low doses of amph etamine. The physiological release of dopamine in substantia nigra and in striatum is dependent on the integrity of this vesicular store.