GABA-mediated neurotransmission in the ventrolateral NTS plays a role in respiratory regulation in the rat.
Our purpose was to determine whether endogenously released GABA in the ventrolateral nucleus of the solitary tract (vlNTS) of the rat influences respiration. Experiments were carried out in anesthetized, vagotomized and spontaneously breathing rats, and diaphragm electromyogram activity was measured while drugs affecting GABAergic neurotransmission were microinjected into the vlNTS and medial NTS (mNTS). Bilateral microinjection of nipecotic acid, 5 or 25 nmol, into the vlNTS (but not in the mNTS) produced dose-dependent increases in inspiratory duration (Ti) frequently culminating in apneustic breathing. Neither unilateral microinjection of bicuculline nor CGP-35348 (GABA(B) receptor antagonist) reversed this response; however, a combination of both GABA receptor antagonists effectively reversed apneustic breathing. Bilateral microinjection of either muscimol or baclofen into the vlNTS mimicked the effect of nipecotic acid. Microinjection of the bicuculline produced apnea, whereas microinjection of CGP-35348 produced a decrease in Ti and an increase in expiratory duration. Immunohistochemical analysis of the vlNTS region revealed GABA(A) receptors densely localized to processes, whereas GABA(B) immunoreactivity was localized to cell bodies. Our data indicate that GABA activity in the vlNTS is important for respiratory function.
Wasserman
Adam M
AM
Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20057, USA.
Ferreira
Manuel
M
Sahibzada
Niaz
N
Hernandez
Yvonne M
YM
Gillis
Richard A
RA
D000818:Animals; D001049:Apnea / Q000139:chemically induced; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology; D002319:Cardiovascular System / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D007150:Immunohistochemistry; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009118:Muscimol / Q000494:pharmacology; D009557:Nipecotic Acids / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000378:metabolism; D012119:Respiration / Q000187:drug effects; D009435:Synaptic Transmission; D020651:Ventral Thalamic Nuclei / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology
D018755:GABA Agonists; D018756:GABA Antagonists; D009557:Nipecotic Acids; D018079:Receptors, GABA; C030278:nipecotic acid; D009118:Muscimol; D018698:Glutamic Acid; C017069:bicuculline methiodide; D005680:gamma-Aminobutyric Acid; D007736:Kynurenic Acid; D001418:Baclofen; D001640:Bicuculline