CHOLECYSTOKININ ACTIVATES AREA POSTREMA NEURONS IN RAT-BRAIN SLICES

Peripheral cholecystokinin (CCK) reduces food intake and triggers the secretion of both oxytocin and corticotropin-releasing hormone. These responses are partially initiated by activation of receptors in the pe ripheral endings of the vagus nerve. However, in vivo studies showing that after vagotomy systemic CCK induces fos activation of neurons in the area postrema (AP) suggest that circulating CCK may directly influ ence the activity of neurons in this structure. The present study was therefore designed to investigate the responsiveness of AP neurons to CCK using in vitro extracellular single-unit recording techniques. Bat h application of 100 nM CCK for 200 s resulted in excitatory responses in 41% and inhibitory effects in 6% of 143 AP neurons tested. Applica tion of multiple doses of CCK (1-100 nM) to single neurons demonstrate d that CCK effects were dose dependent. The firing rate of tested neur ons increased by 48+/-15% in response to 1 nM, by 89+/-22% in response to 10 nM, and by 242+/-77% in response to 100 nM CCK. After we blocka ded synaptic transmission with a low-Ca2+/high-Mg2+ artificial cerebro spinal fluid, the excitatory effects of CCK remained in all nine neuro ns tested. The CCK-receptor antagonist L-364,718 had no significant ef fect on the responses to CCK (P >0.1, n=4), whereas, after perfusion o f slices with the CCKB-receptor antagonist L-365,260, mean responses t o CCK were significantly reduced to 12.6+/-4.7% of the control value ( P <0.001, n=4). These results demonstrate a direct and dose-dependent excitatory action of CCK on AP neurons that is abolished by CCKB-recep tor antagonists. These data emphasize the potential role of AP in proc essing afferent information derived from circulating peptide concentra tions that could be involved in the regulation of food intake.