NEURONAL INHIBITION BY A GABA(B) RECEPTOR AGONIST IN THE ROSTRAL VENTROLATERAL MEDULLA OF THE RAT

We recorded the effects of the gamma-aminobutyric acid class B (GABA(B )) receptor agonist baclofen on neuronal activity in the rat rostral v entrolateral medulla (RVLM) in tissue slices and in vivo. In vitro, ba clofen (3 mu M) produced hyperpolarization (13 of 17), decrease in inp ut resistance (12 of 16), and reduction of spontaneous synaptic activi ty (7 of 14). Baclofen inhibited 84 of 87 spontaneously active neurons recorded extracellularly in vitro. Inhibition was concentration depen dent (0.1-3 mu M, maximum inhibition: 94 +/- 4%, n = 16) and persisted in low-Ca2+/high-Mg2+ medium (n = 19). The GABA(B) receptor antagonis ts CGP-54626A (1 mu M, n = 19), CGP-55845A(1 mu M, n = 15), and 2-hydr oxysaclofen (0.5 mM, n = 3) attenuated inhibition by baclofen (1-3 mu M) but not by muscimol or GABA. In vivo, iontophoresis of baclofen inh ibited 31 of 32 RVLM neurons, including bulbospinal barosensitive (15 of 16) and respiratory ones (7 of 7). CGP-55845A attenuated baclofen i nhibition (6 of 9). Bicuculline attenuated the effect of GABA but not that of baclofen (4 of 4). In summary, RVLM presympathetic neurons hav e somatodendritic GABA(B) receptors that may contribute to baclofen-in duced hypotension in humans.