title: Electrical stimulation of the substantia nigra reticulata: detection of neuronal extracellular GABA in the ventromedial thalamus and its regulatory mechanism using microdialysis in awake rats.
abstract: A combination of electrical stimulation and microdialysis was used to study the nigrothalamic gamma aminobutyric acid (GABA)ergic system and its regulatory mechanisms in awake rats. Extracellular GABA levels in the ventromedial nucleus of the thalamus were detected in 3-min fractions collected before, during and after a 10-min stimulation period of the substantia nigra reticulata. Electrical stimulation of the substantia nigra reticulata increased the GABA levels to 155% of basal values in the ventromedial thalamus only during the first 3-min interval upon stimulation. The increase in GABA levels was tetrodotoxin-dependent, implicating an exocytotic origin. The basal levels of extracellular GABA in the ventromedial thalamus were of nonexocytotic origin. To study the mechanism underlying the fast compensatory response in neuronal GABA release after nigral stimulation, local infusions into the ventromedial thalamus of reuptake inhibitors and GABA antagonists were performed and the effect of nigral stimulation was examined under the various applications. Local infusion of the reuptake inhibitors nipecotic acid (500 microM) and SKF 89976-A (20 and 50 microM) increased extracellular GABA levels to 350%, 180% and 600%, respectively, of basal values in the ventromedial thalamus tetrodotoxin-independently. Under these conditions, the increase in extracellular GABA was absent (nipecotic acid) or suppressed (20% of basal values; SKF 89976-A for both doses), leaving it unsolved whether or not the uptake system was responsible for the fast compensation in neuronal GABA after stimulation. The GABA-A antagonist bicucilline (50 microM) was ineffective when infused locally in the ventromedial thalamus, but prolonged the increase in neuronal GABA release after nigral stimulation; the GABA levels were increased during two 3-min samples to approximately 165%, indicating a functional role for GABA-A receptors in regulating the release of GABA from nigrothalamic GABAergic neurons. The GABA-B receptor antagonist CGP 35348 (50 microM) did not affect GABA levels when infused locally in the ventromedial thalamus and neither affected the response in neuronal GABA after stimulation. This finding does not support a role for GABA-B receptors in controlling the release from the nigrothalamic neurons.
authors.affiliation: Department of Medicinal Chemistry, University Center for Pharmacy, Groningen, The Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: Timmerman
authors.forename: B H
authors.initials: BH
authors.lastname: Westerink
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D008297:Male; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000378:metabolism* / Q000502:physiology; D013788:Thalamus / Q000378:metabolism*; D014851:Wakefulness / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid