The anorectic effect of a chronic peripheral infusion of amylin is abolished in area postrema/nucleus of the solitary tract (AP/NTS) lesioned rats

Abstract

Objective: Neurons in the area postrema/nucleus of the solitary tract (AP/NTS) region mediate amylin's anorectic effect elicited by a single intraperitoneal (i.p.) injection of a low dose (5 microg/kg). Here, we tested if a sustained elevation in amylin levels which was achieved by chronic amylin infusion reduces food intake by acting in the AP/NTS region or, possibly, at other brain sites. Further, we tested the role of the AP/NTS region in mediating the anorectic effects of high doses of amylin and its receptor agonist salmon calcitonin (sCT) after an acute single injection.

Design: Amylin (2 microg/kg/h) was chronically infused i.p. by osmotic minipumps in AP/NTS-lesioned (AP-X) or sham-lesioned (SHAM) rats. For the acute experiments, amylin or sCT was injected i.p. at doses of 0.5 (only sCT), 5 or 50 microg/kg. Food intake was measured by a computerized system. Body weight was assessed by manually weighing the rats.

Results: Amylin significantly reduced cumulative food intake for about 7 days in SHAM but not in AP-X rats. Amylin's effect in SHAM rats was mainly due to a reduction of the size of nocturnal meals (eg average meal size during the first four dark phases; SHAM, NaCl 4.1+/-0.6 vs amylin 2.6+/-0.4 g; n=6, P<0.05; AP-X, 2.6+/-0.3 vs 3.7+/-0.3) while light phase food intake was unaffected. Body weight gain over the whole 14 day infusion period was reduced by amylin in SHAM (NaCl 61+/-6 vs amylin 46+/-4 g; P<0.05) but not in AP-X rats (54+/-4 vs 62+/-4). After single injection, the anorectic effect of high doses of amylin and sCT (50 microg/kg) was attenuated, but not abolished, in AP-X rats.

Conclusion: We conclude that, under our experimental conditions, neurons in the AP/NTS region are necessary for chronically elevated peripheral amylin to reduce food intake in rats. High doses of amylin, however, may be able to overrun these receptors and reduce feeding by acting at other brain sites.