Extracellular gamma-aminobutyric acid in the substantia nigra reticulata measured by microdialysis in awake rats: effects of various stimulants.
The gamma-aminobutyric acid (GABA)-ergic system in the substantia nigra reticulata (SNR) was challenged by local infusion of various receptor-specific agents to obtain additional information on the physiological significance of extracellular GABA levels as measured by microdialysis in awake rats. Notwithstanding in vitro results, basal extracellular GABA levels were not affected by local infusion of the GABA-A agonist muscimol or by infusion of the GABA-B agonist baclofen. Upon a dopaminergic challenge, the D2 agonist LY 171555 was equally ineffective, but the D1 agonist induced an increase in extracellular GABA levels, which persisted in the presence of tetrodotoxin (TTX). Using excitatory amino acids, kainic acid was ineffective in modulating GABA levels, whereas N-methyl-D-aspartate induced an increase in extracellular GABA levels, again persisting when co-infused with TTX. The functional significance of TTX-independent changes in extracellular GABA levels is discussed.
Department of Medicinal Chemistry, University of Groningen, The Netherlands.
W
W
Timmerman
B H
BH
Westerink
D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D018682:GABA Agents / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000697:Central Nervous System Stimulants; D018491:Dopamine Agonists; D018682:GABA Agents; D016194:Receptors, N-Methyl-D-Aspartate; D005680:gamma-Aminobutyric Acid