Relative involvement of globus pallidus and subthalamic nucleus in the regulation of somatodendritic dopamine release in substantia nigra is dopamine-dependent

• Published in: Neuroscience 2003-01, Vol.119 (3), p.777-786
• Main Authors: Cobb, W.S, Abercrombie, E.D
• Format: Article
• Language: English
• Subjects: Animals; basal ganglia; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Dendrites - metabolism; Dendrites - ultrastructure; Dopamine - metabolism; Dopamine Antagonists - pharmacology; Drug Synergism; Extracellular Space - drug effects; Extracellular Space - metabolism; Fundamental and applied biological sciences. Psychology; GABA; GABA Antagonists - pharmacology; GABA-A Receptor Antagonists; gamma-Aminobutyric Acid - metabolism; Globus Pallidus - cytology; Globus Pallidus - drug effects; Globus Pallidus - metabolism; glutamate; Glutamic Acid - metabolism; Haloperidol - pharmacology; Male; Microdialysis; Muscimol - pharmacology; Neural Inhibition - drug effects; Neural Inhibition - physiology; Neural Pathways - cytology; Neural Pathways - drug effects; Neural Pathways - metabolism; Parkinson Disease - metabolism; Parkinson Disease - physiopathology; Parkinson's disease; Rats; Rats, Sprague-Dawley; Receptors, GABA-A - metabolism; Substantia Nigra - cytology; Substantia Nigra - metabolism; Subthalamic Nucleus - cytology; Subthalamic Nucleus - drug effects; Subthalamic Nucleus - metabolism; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(03)00071-X

Previously, we have shown that GABA A receptors and glutamate receptors in substantia nigra play distinct roles in the regulation of somatodendritic dopamine release. GABAergic input to substantia nigra was found to be the primary determinant of the level of spontaneous somatodendritic dopamine release. In contrast, acute blockade of dopamine receptors by systemic haloperidol administration produced an increase in somatodendritic dopamine release in substantia nigra that was found to be dependent exclusively upon activation of nigral glutamate receptors. The focus of the present study was to identify anatomical structures that may participate in the differential regulation of somatodendritic dopamine release by GABA and glutamate under these two conditions. To this end, we pharmacologically inhibited the activity of either globus pallidus or subthalamic nucleus using microinfusion of the GABA A receptor agonist muscimol. The effects of these manipulations on spontaneous efflux of somatodendritic dopamine and on increases in this measure produced by systemic haloperidol administration were determined in ipsilateral substantia nigra using in vivo microdialysis. As observed previously, administration of haloperidol (0.5 mg/kg, i.p.) significantly increased extracellular dopamine in substantia nigra. Microinfusion of muscimol (400 ng/200 nl) into globus pallidus also produced a significant increase in somatodendritic dopamine efflux. When haloperidol was administered systemically in conjunction with microinfusion of muscimol into globus pallidus, an increase in nigral dopamine efflux was observed that was significantly greater than that which was produced singly by muscimol microinfusion into globus pallidus or by systemic haloperidol administration. The additive nature of the increases in somatodendritic dopamine release produced by these two manipulations indicates that independent neural circuitries may be involved. Inactivation of subthalamic nucleus by microinfusion of muscimol (200 ng/100 nl) had no effect on spontaneous somatodendritic dopamine efflux. Muscimol application into subthalamic nucleus, however, completely abolished the stimulatory effect of systemic haloperidol on dendritic dopamine efflux in substantia nigra. The present data extend our previous findings by demonstrating: 1) an important involvement of globus pallidus efferents in the GABAergic regulation of somatodendritic dopamine efflux in substantia nigra under normal conditions and, 2