Neuronal inhibition by a GABAB receptor agonist in the rostral ventrolateral medulla of the rat.
We recorded the effects of the gamma-aminobutyric acid class B (GABAB) receptor agonist baclofen on neuronal activity in the rat rostral ventrolateral medulla (RVLM) in tissue slices and in vivo. In vitro, baclofen (3 microM) produced hyperpolarization (13 of 17), decrease in input resistance (12 of 16), and reduction of spontaneous synaptic activity (7 of 14). Baclofen inhibited 84 of 87 spontaneously active neurons recorded extracellularly in vitro. Inhibition was concentration dependent (0.1-3 microM, maximum inhibition: 94 +/- 4%, n = 16) and persisted in low-Ca2+/high-Mg2+ medium (n = 19). The GABAB receptor antagonists CGP-54626A (1 microM, n = 19), CGP-55845A (1 microM, n = 15), and 2-hydroxysaclofen (0.5 mM, n = 3) attenuated inhibition by baclofen (1-3 microM) but not by muscimol or GABA. In vivo, iontophoresis of baclofen inhibited 31 of 32 RVLM neurons, including bulbospinal barosensitive (15 of 16) and respiratory ones (7 of 7). CGP-55845A attenuated baclofen inhibition (6 of 9). Bicuculline attenuated the effect of GABA but not that of baclofen (4 of 4). In summary, RVLM presympathetic neurons have somatodendritic GABAB receptors that may contribute to baclofen-induced hypotension in humans.
Li
Y W
YW
Department of Pharmacology, University of Virginia, Charlottesville 22908.
Guyenet
P G
PG
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D003470:Culture Media; D004594:Electrophysiology; D005110:Extracellular Space / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D007425:Intracellular Membranes / Q000502:physiology; D008274:Magnesium / Q000494:pharmacology; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009433:Neural Inhibition; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000145:classification / Q000502:physiology*
D003470:Culture Media; D018755:GABA Agonists; D018756:GABA Antagonists; D018079:Receptors, GABA; D001418:Baclofen; D008274:Magnesium; D002118:Calcium