GABA(A) and GABA(B) receptors modulating basal and footshock-induced nitric oxide releases in rat prefrontal cortex.
Using an in vivo brain microdialysis technique, we measured extracellular levels of nitric oxide (NO) metabolites (NO(x)(-)) in the medial prefrontal cortex (mPFC) upon perfusion of gamma-aminobutyric acid (GABA) receptor antagonists as well as agonists, and also examined the effects of GABA receptor agonists on mild intermittent footshock-induced NO releases in the mPFC in conscious rats. Perfusion of either bicuculline methiodide, a GABA(A) receptor antagonist, or saclofen, a GABA(B) receptor antagonist, through a microdialysis probe resulted in dose-dependent increases in NO(x)(-) levels. Higher-dose perfusion of either muscimol (50 microM), a GABA(A) receptor agonist, or baclofen (250 microM), a GABA(B) receptor agonist resulted in a significant decrease in NO(x)(-) levels. The elevated levels of NO(x)(-) after mild intermittent footshock were attenuated by perfusion of either muscimol (10 microM) or baclofen (50 microM), either of which alone did not affect basal NO(x)(-) levels. These findings are likely to provide helpful clues to our understanding of the inhibitory modulation of basal and footshock-induced NO metabolites releases by GABA(A) and GABA(B) receptors in the mPFC.
Department of Psychiatry, Miyazaki Medical College, 5200 Kihara, Kiyotake-cho, Miyazaki-gun, 889-1692, Miyazaki, Japan.
Y
Y
Ishizuka
Y
Y
Ishida
Q H
QH
Jin
Y
Y
Mitsuyama
H
H
Kannan
D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001640:Bicuculline / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D005110:Extracellular Space / Q000737:chemistry; D018755:GABA Agonists / Q000008:administration & dosage; D018756:GABA Antagonists / Q000008:administration & dosage; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D008297:Male; D017551:Microdialysis; D009118:Muscimol / Q000008:administration & dosage; D009566:Nitrates / Q000032:analysis; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000032:analysis; D010477:Perfusion; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*
D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D009566:Nitrates; D009573:Nitrites; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D009118:Muscimol; D009569:Nitric Oxide; C017069:bicuculline methiodide; D001418:Baclofen; C080629:saclofen; D001640:Bicuculline