Mechanism of action of baclofen in rat dorsal motor nucleus of the vagus

Using whole cell patch-clamp recordings, we investigated the effects of the GABA(B) receptor agonist baclofen in thin slices of rat brain stem contain ing identified gastric- or intestinal-projecting dorsal motor nucleus of th e vagus (DMV) neurons. Perfusion with baclofen (0.1-100 muM) induced a conc entration-dependent outward current (EC50, 3 muM) in 54% of DMV neurons wit h no apparent differences between gastric- and intestinal-projecting neuron s. The outward current was attenuated by pretreatment with the selective GA BA(B) antagonists saclofen and 2-hydroxysaclofen, but not by the synaptic b locker TTX, indicating a direct effect at GABA(B) receptors on DMV neurons. Using the selective ion channel blockers barium, nifedipine, and apamin, w e showed that the outward current was due to effects on potassium and calci um currents as well as calcium-dependent potassium currents. The calcium-me diated components of the outward current were more prominent in intestinal- projecting neurons than in gastric- projecting neurons. These data indicate that although baclofen inhibits both intestinal- and gastric-projecting ne urons in the rat DMV, its mechanism of action differs among the neuronal su bpopulations.