Effects of intraamygdaloid microinjections of acylated-ghrelin on liquid food intake of rats.

Ghrelin (Ghr) has two main forms in the blood: the acylated (A-Ghr) and non-acylated (NA-Ghr) Ghr. A-Ghr was discovered as a potent growth hormone (GH) secretion increasing substance acting on GH secretagouge receptor (GHS-R) type 1a. A-Ghr facilitates food intake after its i.p., i.c.v. or direct hypothalamic application. Immunohistological assays identified projections of ghrelinergic neurons to the basolateral nucleus (ABL) of the amygdala (AMY). A-Ghr injected into the hypothalamus caused c-Fos overexpression in the AMY area that has an important role in food intake and body weight regulation. In separate experiments, liquid food intake of male wistar rats was measured after bilateral intraamygdalar or bilateral i.c.v. administration of A-Ghr (25, 50, 100, 250, and 500 ng/side or 500 and 1000 ng/side, A-Ghr dissolved in 0.15 M sterile NaCl/0.4 microl or 1 microl, respectively). In the ABL, A-Ghr microinjections in the 50-250 ng dose range resulted in significant decrease of food intake. The 25 and 500 ng had no effect. Action of 50 ng (14.83 pmol) or 100 ng (30.16 pmol) A-Ghr was eliminated by 15 ng (16.13 pmol) or 30 ng (32.25 pmol) GHS-R antagonist (D-Lys3-GHRP-6) pretreatment. The administration of 30 ng D-Lys3-GHRP-6 in itself had no influence on feeding. I.c.v. applied 1000 ng A-Ghr increased liquid food intake. Our results are the first ones reporting that A-Ghr injected into the ABL resulted in a decrease of liquid food consumption, within a limited dose range. This is a receptor-linked effect because it was eliminated by a GHS-R specific antagonist.