GABA(B) receptors on vagal afferent pathways: peripheral and central inhibition

To investigate GABA(B) receptors along vagal afferent pathways, we recorded from vagal afferents, medullary neurons, and vagal efferents in ferrets. B aclofen (7-14 mu mol/kg iv) reduced gastric tension receptor and nucleus tr actus solitarii neuronal responses to gastric distension but not gastroduod enal mucosal receptor responses to cholecystokinin (CCK). GABA(B) antagonis ts CGP-35348 or CGP-62349 reversed effects of baclofen. Vagal efferents sho wed excitatory and inhibitory responses to distension and CCK. Baclofen (3 nmol icv or 7-14 mu mol/kg iv) reduced both distension response types but r educed only inhibitory responses to CCK. CGP-35348 (100 nmol icv or 100 mu mol/kg iv) reversed baclofen's effect on distension responses, but inhibito ry responses to CCK remained attenuated. They were, however, reversed by CG P-62349 (0.4 nmol icv). In conclusion, GABA(B) receptors inhibit mechanosen sitivity, not chemosensitivity, of vagal afferents peripherally. Mechanosen sory input to brain stem neurons is also reduced centrally by GABA(B) recep tors, but excitatory chemosensory input is unaffected. Inhibitory mechano- and chemosensory inputs to brain stem neurons (via inhibitory interneurons) are both reduced, but the pathway taken by chemosensory input involves GAB A(B) receptors that are insensitive to CGP-35348.