Atsushi Ohgushi

Intracerebroventricular injection of ghrelin and growth hormone releasing factor inhibits food intake in neonatal chicks

Growth hormone releasing factor (GRF) is known to stimulate feeding of rats. Ghrelin, a novel growth hormone (GH)-releasing acylated peptide, was recently isolated from rat stomach. It also stimulates the release of GH from the anterior pituitary through the GH secretagogue receptor (GHS-R) and feeding in the rat. We have investigated the effects of ghrelin and GRF on food intake of the neonatal chick. In Experiment 1, 0, 1.25, 2.5 and 5 microg of ghrelin were administered intracerebroventricularly (i.c.v.) to ad libitum fed birds. In Experiment 2, the effect of (i.c.v.) injection of 0, 1.25, 2.5 and 5 microg of GRF was investigated. Both peptides strongly inhibited food intake of the chick during the 2-h post-injection period. In the third experiment, 0, 0.5, 1 and 2 microg of ghrelin was injected i.c.v. in chicks previously deprived of food for 3 h. Food intake was again inhibited by ghrelin in a dose-dependent manner. These results suggest that the mechanisms for feeding of the neonatal chick through GH release are different from mammals.

Intracerebroventricular injection of agouti-related protein attenuates the anorexigenic effect of alpha-melanocyte stimulating hormone in neonatal chicks

It is well known that alpha-melanocyte stimulating hormone (alpha-MSH) inhibits feeding via melanocortin receptor-4 (MC4R) in the mammalian brain. The anorexigenic effect of alpha-MSH is attenuated by agouti-related protein (AGRP), an antagonist for MC4R. Present studies were carried out to clarify whether human AGRP (86-132) antagonizes the anorexigenic effect of alpha-MSH in broiler chicks. Intracerebroventricular injection of AGRP attenuated the anorexigenic effect of alpha-MSH. Furthermore, AGRP stimulated food intake of layer-type chicks under an ad libitum feeding condition but not broiler chicks, suggesting that the orexigenic effect of AGRP is different between two breeds. These also imply that the extent of the anorexigenic effect of endogenous alpha-MSH is different among two breeds. This may be a part of the difference in food intake between two breeds.

Central administration of α-melanocyte stimulating hormone inhibits fasting- and neuropeptide Y-induced feeding in neonatal chicks

In the present study, the effect of intracerebroventricular (i.c.v.) administration of alpha-melanocyte stimulating hormone (alpha-MSH) on food intake of neonatal chicks was examined. In experiment 1, i.c. v. injection of alpha-MSH (0.04, 0.2 and 1 microg) significantly inhibited food intake of 3-h fasted chicks in a dose-dependent manner. In experiment 2, alpha-MSH strongly inhibited neuropeptide Y-induced feeding when neuropeptide Y (2.5 microg) and several doses of alpha-MSH were given simultaneously i.c.v. These results suggest that alpha-MSH plays an important role in the regulation of food intake of neonatal chicks.

Relationships between feeding and locomotion behaviors after central administration of CRF in chicks

The effect of intracerebroventricular injection of corticotropin-releasing factor (CRF) on various behaviors in chicks was determined at 15-min intervals over a 30-min period. Food intake of chicks was significantly decreased, and pecking rhythm was significantly delayed by CRF during the first 15-min post-injection. The similar tendencies were observed in the second 15-min post-injection, but not significantly different. Stepping, as an indicator of locomotion, was not different at 15-min post-injection, but was increased by CRF, thereafter. These results suggest that CRF acts within the central nervous system to decrease food intake and increase locomotion in the chick.

Central administration of cocaine- and amphetamine-regulated transcript inhibits food intake in chicks.

The present study was done to clarify whether intracerebroventricular (ICV) injection of cocaine- and amphetamine-regulated transcript (CART) affects feeding in chicks. ICV injection of CART significantly inhibited fasting-induced feeding of broiler chicks. In layer chicks, on the other hand, CART inhibited food intake in birds with ad libitum access to feed but only weakly affected intake of fasted birds. In addition, the ICV injection of CART attenuated neuropeptide Y (NPY)-induced feeding in both broiler and layer chicks. These results indicate that CART is one of the important regulators of feeding in chicks, but the suppressive effect on feeding is somewhat different between strains. Furthermore, the present study also demonstrates that CART interacts with NPY in the central nervous system to regulate feeding in chicks.

Suppression of food intake induced by corticotropin-releasing factor family in neonatal chicks.

Corticotropin-releasing factor (CRF), urocortin and urotensin I share amino acid sequences, and they inhibit food intake in mammals. CRF plays a potent role in decreasing food intake in avian species, but the effects of urocortin and urotensin I have not been investigated. Therefore, the effect of these three peptides on food intake in the neonatal chick was compared. In Experiment 1, birds were injected intracerebroventricularly (i.c.v.) with either 0, 0.01, 0.1 or 1 microg of urocortin following a 3-h fast, and food intake was measured for 2 h post-injection. Food intake was suppressed in a dose-dependent manner. Using a similar design in Experiment 2, the effect of urotensin I was investigated. Urotensin I appeared to suppress food intake in neonatal chicks more than urocortin did. In Experiment 3, the efficacy of CRF, urocortin and urotensin I was directly compared using one dose, 0.1 microg. The results indicated that the suppressive effect on food intake was strongest for CRF followed by urotensin I, then urocortin. These results suggest that the structure of receptors for the CRF family in chicks may be somewhat different than in mammals.

Feeding responses to several neuropeptide Y receptor agonists in the neonatal chick

Neuropeptide Y is one of the most potent neuropeptides known to induce feeding in animals, and has been suggested to be a physiological signal for food intake. It has been also reported that intracerebroventricular injection of neuropeptide Y stimulates feeding behavior of the neonatal chick. There are many neuropeptide Y receptor agonists that have not been investigated in feeding response of the neonatal chick. The aim of this study is to elucidate whether central injection of several neuropeptide Y receptor agonists stimulates feeding of the neonatal chick over 2 h. We found that central injections of [Leu(31), Pro(34)]neuropeptide Y, peptide YY, human pancreatic polypeptide and rat pancreatic polypeptide significantly stimulated food intake of neonatal chicks throughout the 2-h post-injection period. Neuropeptide Y-(13-36) significantly stimulated feeding at 30 min, but not thereafter. [D-Trp(32)]neuropeptide Y stimulated feeding at 60 and 120 min, but not 30 min, post-injection. Central administration of rat pancreatic polypeptide, which does not increase food intake in rats, stimulated feeding in chicks. This result reflects structural differences of the neuropeptide Y receptor subtypes and/or differences in mechanisms stimulating feeding behavior between mammals and chickens. In conclusion, neuropeptide Y receptor agonists, except for neuropeptide Y-(13-36), are potent stimulators of food intake in the neonatal chick.

Interaction of corticotropin-releasing factor and glucagon-like peptide-1 on behaviors in chicks.

Both corticortropin-releasing factor (CRF) and glucagon-like peptide-1 (GLP-1) inhibit food intake of chicks, but they also produce other behaviors. The present experiments were undertaken to clarify the interaction of CRF and GLP-1 regarding their anorectic actions as well as other behaviors. In Experiment 1, birds were injected intracerebroventricularly (i.c.v.), following a 3-h fast, with either saline, 0.1 microg of CRF, 0.1 microg of CRF+0.1 microg of GLP-1 or 0.1 microg of CRF+1 microg of GLP-1, and food intake was measured for 2 h. The injection of CRF decreased food intake, and CRF injected with GLP-1 suppressed food intake for up to 2 h. Birds were treated similarly in Experiment 2 in which the doses of CRF and GLP-1 were reversed. GLP-1 strongly suppressed food intake, and this effect was augmented by coadministration of CRF. In Experiment 3, the behaviors of chicks injected with saline, CRF (0.1 microg), GLP-1 (0.1 microg) or CRF (0.1 microg)+GLP-1 (0.1 microg) were monitored for the numbers of steps, vocalization and locomotion. Chicks were excited, moved more and vocalized loudly following injection of CRF, whereas an opposite response was seen with GLP-1. The behaviors were intermediate following the coinjection of the two peptides. In conclusion, CRF and GLP-1 interact in the chick brain, but the response depends on the behavior being measured.

Brain-derived mast cells could mediate histamine-induced inhibition of food intake in neonatal chicks

In the present study, the effect of intracerebroventricular (i.c.v.) administration of histamine on food intake of neonatal chicks was examined over 2 h. Histamine (100, 200 or 400 nmol, respectively) was injected in the lateral ventricle of 2-day-old chicks, and cumulative food intakes were measured. i.c.v. injection of histamine significantly inhibited food intake in a dose-dependent manner. In addition, compound 48/80, which causes degranulation of mast cells and release of histamine, or thioperamide, which is an antagonist of the histamine H3 autoreceptor and increases histamine release from histaminergic nerve terminals, was injected i.c.v. to clarify whether mast cell- or neuron-derived histamine in the central nervous system of chicks is essential to the feeding inhibition. Central administration of compound 48/80 inhibited food intake with a dose-dependent manner, but thioperamide had no effect on feeding. An inhibitor of mast cell degranulation, sodium cromoglycate, somewhat attenuated food intake inhibited by compound 48/80. These results suggest that brain-derived mast cells could be a major source of histamine in the inhibition of food intake of neonatal chicks.

Intracerebroventricular injection of pipecolic acid inhibits food intake and induces sleeping-like behaviors in the neonatal chick

It has been demonstrated that L-pipecolic acid (L-PA), a major metabolic intermediate of L-Lysine (L-Lys) in the brain, is involved in the functioning of Gamma-aminobutyric acid. In the present work the effect of intracerebroventricular (i.c.v.) administration of L-PA, and its relatives, on food intake and behavior in neonatal chicks was investigated. The i.c.v. injection of 1 mg of L-PA and D-PA significantly inhibited food intake during the 2 h following injection, whereas greater than 2 mg of L-Lys was required to inhibit food intake. In behavioral tests, the i.c.v. injection of L-PA reduced active wakefulness and feeding behavior while inducing sleeping-like behavior in chicks. These results suggest that L-PA has an important role for the regulation of behaviors in the neonatal chick after conversion from L-Lys in the brain.