The regulation of dopamine release from nigrostriatal neurons in conscious rats: the role of somatodendritic autoreceptors

Abstract

Drugs were infused into the substantia nigra of the rat brain via a microdialysis probe, and the extracellular concentration of dopaminc (DA) and 3,4-dihydroxyphenylacelic acid was recorded from a second dialysis probe implanted in the ipsilateral striatum. This approach allowed the evaluation of the sensitivity of nigral autoreceptors to various d 1 and D 2 agonists and antagonists in conscious animals. Intranigral administration of the specific D 2 agonists. quinpirole (LY 171555: 1, 10 and 50 μmol/l) and (−)-N-0437 (10 μmol/l), decreased the output of striatal dopamine, whereas the specific D 2 antagonist, (—)-sulpiridc (10 and 50 μmol/l), stimulated slightly the release of dopamine from the ipsilateral corpus striatum. Intranigral administration of the D 1 agonist, SKF 38393 (100 μmol/l). and the D 1 antagonist, SCH 23390 (KM) μmol/l), was without effect on the release of striatal dopamine. The results indicate that release-controlling autoreceptors on nerve terminals and autoreceptors controlling impulse flow in the nigra contribute equally to the decrease of striatal DA release caused by a high systemic dose of D 2 agonists. The stimulating effect of D 2 antagonists on the release of DA is mainly caused by release-controlling autoreceptors localized on nerve terminals. The autoreceptors in the nigra controlling impulse flow contributed somewhat less (about 20%) to this effect. Advantages and disadvantages of the use of a microdialysis probe to deliver drugs to restricted brain areas are discussed.