Differential effects of D1 and D2 dopamine receptor agonists on substantia nigra pars reticulata neurons.
ABSTRACT Dopamine was shown in previous studies to exert a dual effect on non-dopaminergic neurons of the substantia nigra pars reticulata: it increases the firing rates of about 50% of cells, and consistently lessens the ability of iontophoretically applied or endogenously released GABA to inhibit their firing. These studies were undertaken to determine (1) whether the two effects could occur independently and, (2) whether different dopamine receptor subtypes might mediate the two responses. Extracellular, single unit activities of pars reticulata neurons were monitored in male rats anesthetized with chloral hydrate. Repeated 30-s iontophoretic pulses of GABA were delivered at an ejection current sufficient to inhibit cell firing by at least 50%, but not totally. After establishing a consistent response to GABA, co-iontophoresis of a test compound was initiated to determine its effects on basal firing rates and responsiveness to GABA. When acetylcholine and glutamate were evaluated in the test paradigm using ejection currents which excited cells by 54.0 +/- 4.9%, neither compound consistently altered the inhibition elicited by GABA. This confirmed that increases in cell firing could occur without concurrent GABA-attenuating effects, and supported the contention that the dual effects of dopamine could be dissociated and perhaps independently mediated. To examine whether the effects of dopamine involve actions at different dopamine receptor subtypes within the nigra, the D1 agonist SKF 38393 and the D2 agonist LY 171555 were substituted in the procedure. Applications of R,S(+/-)-SKF 38393 caused current-dependent increases in firing with a maximal increase at 8 nA of 55 +/- 18% above baseline (n = 14). The excitatory effect appeared to be D1-mediated since R(+)-SKF 38393, but not the inactive S(+)-enantiomer, could elicit the response. Conversely, graded applications of LY 171555 caused only occasional and more modest increases in basal activities, but consistently and markedly attenuated responses to GABA, decreasing GABA's inhibitory potency by 60.9 +/- 4.3% at 10 nA (n = 17). These results provide support for discrete roles of D1 and D2 receptors in substantia nigra pars reticulata, and suggest mechanistically distinct ways by which dendritically released dopamine could act to modify basal ganglia output from this region.
- Dendritic Transmitter Release, Edited by Mike Ludwig, 12/2004: pages 85-99; Kluwer Academic/Plenum.
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ABSTRACT: During the last few years, our understanding of basal ganglia anatomy and function has undergone major changes. It is now recognized that the basal ganglia participate in larger circuits that also involve regions of the cerebral cortex, thalamus, and brain stem. These circuits subserve motor and non-motor functions, and occupy separate territories within the basal ganglia. Specific abnormalities in the function of motor-related basal ganglia areas are thought to contribute to the signs and symptoms of movement disorders such as Parkinson's disease or dystonia, while abnormalities in non-motor circuits may be relevant for the pathophysiology of some of the neuropsychiatric disorders. The insight that relatively local abnormalities in the basal ganglia may contribute to the pathophysiology of movement disorders has resulted in renewed interest in focal neurosurgical treatments for these conditions, such as deep brain stimulation, ablative techniques, or transplantation. This chapter discusses the results of anatomical and physiological studies that are relevant for our current understanding of the motor functions of the basal ganglia, and for the use of neurosurgical interventions in movement disorders. Keywords:striatum–putamen–globus pallidus–subthalamic nucleus–substantia nigra–dopamine–Parkinson's disease–dystonia12/2007: pages 1-32;
- Annals of the New York Academy of Sciences 12/2006; 654(1):128 - 135. · 4.38 Impact Factor