Activation of nigral and pallidal dopamine D1-like receptors modulates basal ganglia outflow in monkeys.
Studies of the effects of dopamine in the basal ganglia have focused on the striatum, whereas the functions of dopamine released in the internal pallidal segment (GPi) or in the substantia nigra pars reticulata (SNr) have received less attention. Anatomic and biochemical investigations have demonstrated the presence of dopamine D1-like receptors (D1LRs) in GPi and SNr, which are primarily located on axons and axon terminals of the GABAergic striatopallidal and striatonigral afferents. Our experiments assessed the effects of D1LR ligands in GPi and SNr on local gamma-aminobutyric acid (GABA) levels and neuronal activity in these nuclei in rhesus monkeys. Microinjections of the D1LR receptor agonist SKF82958 into GPi and SNr significantly reduced discharge rates in GPi and SNr, whereas injections of the D1LR antagonist SCH23390 increased firing in the majority of GPi neurons. D1LR activation also increased bursting and oscillations in neuronal discharge in the 3- to 15-Hz band in both structures, whereas D1LR blockade had the opposite effects in GPi. Microdialysis measurements of GABA concentrations in GPi and SNr showed that the D1LR agonist increased the level of the transmitter. Both findings are compatible with the hypothesis that D1LR activation leads to GABA release from striatopallidal or striatonigral afferents, which may secondarily reduce firing of basal ganglia output neurons. The antagonist experiments suggest that a dopaminergic "tone" exists in GPi. Our results support the finding that D1LR activation may have powerful effects on GPi and SNr neurons and may mediate some of the effects of dopamine replacement therapies in Parkinson's disease.
Kliem
Michele A
MA
Yerkes National Primate Center, Emory University, School of Medicine, 954 Gatewood Road, Atlanta, GA 30322, USA.
Maidment
Nigel T
NT
Ackerson
Larry C
LC
Chen
Sugong
S
Smith
Yoland
Y
Wichmann
Thomas
T
D000818:Animals; D001479:Basal Ganglia / Q000502:physiology*; D001552:Benzazepines / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004594:Electrophysiology; D008253:Macaca mulatta; D017551:Microdialysis; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D013378:Substantia Nigra / Q000502:physiology*
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; C071262:SK&F 82958