CCK MODULATES INHIBITORY SYNAPTIC TRANSMISSION IN THE SOLITARY COMPLEX THROUGH CCKB SITES

THE CCK(B) antagonists L-365,260 and PD134308 and the CCK, antagonist L-364, 718 were applied to neurones of the rat solitary,complex (SC) isolated in brainstem slices, while recording either intracellularly or by whole-cell patch-clamp. The CCK(B) antagonists increased the amplitude of spontaneous or solitary tract-evoked Cl--dependent inhibitory synaptic events by 25 +/- 5% in 5/7 neurones. These events were identified as (1) reversed spontaneous potentials, (2) reversed multisynaptic potentials and (3) outward currents blocked by the GABA(A) antagonist bicuculline. The CCK(B) antagonists had no postsynaptic action and increased excitatory synaptic events by 16 +/- 5% in only 3/9 neurones. The CCK(A) antagonist depolarized neurones but had no effect on synaptic events. Results suggest that CCK, released from the SC tissue, modulates GABAergic interneurones through CCK(B) sites. This mechanism could contribute to panic attacks, probably mediated by CCK(B) receptors.