The regulation of dopamine release from nigrostriatal neurons in conscious rats: the role of somatodendritic autoreceptors.
Drugs were infused into the substantia nigra of the rat brain via a microdialysis probe, and the extracellular concentration of dopamine (DA) and 3,4-dihydroxyphenylacetic 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 D1 and D2 agonists and antagonists in conscious animals. Intranigral administration of the specific D2 agonists, quinpirole (LY 171555; 1, 10 and 50 mumol/l) and (-)-N-0437 (10 mumol/l), decreased the output of striatal dopamine, whereas the specific D2 antagonist, (-)-sulpiride (10 and 50 mumol/l), stimulated slightly the release of dopamine from the ipsilateral corpus striatum. Intranigral administration of the D1 agonist, SKF 38393 (100 mumol/l), and the D1 antagonist, SCH 23390 (100 mumol/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 D2 agonists. The stimulating effect of D2 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.
Department of Medicinal Chemistry, University of Groningen, The Netherlands.
M
M
Santiago
B H
BH
Westerink
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003243:Consciousness; D003342:Corpus Striatum / Q000378:metabolism / Q000648:ultrastructure; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists; D004873:Ergolines / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology*; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013469:Sulpiride / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology
D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D004873:Ergolines; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D015102:3,4-Dihydroxyphenylacetic Acid; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; C047508:rotigotine; D004298:Dopamine