Infusion of the amylin antagonist AC 187 into the area postrema increases food intake in rats

According to previous studies, the area postrema (AP) of the hindbrain may play an important role in mediating the anorectic effect of the pancreatic hormone amylin. Peripheral amylin has been suggested to directly act on AP neurons to bring about its ancrectic effect. Cyclic GMP may act as second messenger in this regard. In the present study, we wanted to further delineate the role of the AP in amylin's effect and to find out whether endogenous amylin might reduce feeding via the AP. Rats with chronic cannulas aiming at the All were infused with various doses of amylin, its agonist salmon calcitonin (sCT) or a cyclic guanosine monophosphate (cGMP) analogue. Amylin and sCT inhibited food intake for about 2 h after food presentation, mainly by reducing meal size when infused into the AP [e.g., 1 h food intake after amylin (0.4 mug/rat) infusion in 12-h deprived rats: NaCl 4.0 +/- 0.5 vs. amylin 2.4 +/- 0,5, P<.05]. The effect was comparable in ad libitum fed and 12-h food-depdved rats with a minimal effective dose of 0.04 mug/rat. Similar to amylin and sCT, the cGMP analogue 8-Br-cGMP (200 nmol/rat) also reduced food intake and meal size. Infusion of the amylin antagonist AC 187 (30 mug) into the AP significantly reduced the anorectic effect induced by an intraperitoneal injection of amylin (5 mug/kg). Furthermore, AC 187 alone increased feeding when infused into the AP. This study is in line with previous work pointing to an important role of the AP in mediating the anorectic effect of amylin. Furthermore, we provide evidence for a physiological role of endogenous amylin to reduce food intake. This may also involve an action via the AP. (C) 2004 Elsevier Inc. All rights reserved.