Submitted on February 15, 2007
Accepted on July 10, 2007
Activation of Nigral and Pallidal Dopamine D1-Like Receptors Modulates Basal Ganglia Outflow in Monkeys
Michele Ann Kliem1, Nigel T Maidment2, Larry C Ackerson2, Sugong Chen3, Yoland Smith3, and Thomas Wichmann4*
1 Yerkes National Primate Center, Emory University, Atlanta, Georgia, United States
2 Psychiatry and Biobehavioral Sciences, Neuropsychiatric Institute, University of California, Los Angeles, Los Angeles, California, United States
3 Yerkes National Primate Center, Department of Neurology, Emory University, Atlanta, Georgia, United States
4 Yerkes National Primate Center, Department of Neurology, Emory University, Atlanta, Georgia, United States; Atlanta, Georgia, United States
* To whom correspondence should be addressed. E-mail: twichma{at}emory.edu.
Studies of the effects of dopamine in the basal ganglia have focused on the striatum, while 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 striato-pallidal and striato-nigral afferents. Our experiments assessed the effects of D1LR ligands in GPi and SNr on local 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, while 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 3-15 Hz band in both structures, while 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 striato-pallidal or striato-nigral 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.
