The role of GABAergic system on the inhibitory effect of ghrelin on food intake in neonatal chicks.
ABSTRACT Ghrelin is a gut-brain peptide that has a stimulatory effect on food intake in mammals. In contrast, this peptide decreases food intake in neonatal chicks when injected intracerebroventricularly (ICV). In mammals, neuropeptide Y (NPY) mediates the orexigenic effect of ghrelin whereas in chicks it appears that corticotrophin releasing factor (CRF) is partially involved in the inhibitory effect of ghrelin on food intake. Gamma aminobutyric acid (GABA) has a stimulatory effect on food intake in mammals and birds. In this study we investigated whether the anorectic effect of ghrelin is mediated by the GABAergic system. In Experiment 1, 3h-fasted chicks were given an ICV injection of chicken ghrelin and picrotoxin, a GABA(A) receptors antagonist. Picrotoxin decreased food intake compared to the control chicks indicating a stimulatory effect of GABA(A) receptors on food intake. However, picrotoxin did not alter the inhibitory effect of ghrelin on food intake. In Experiment 2, THIP hydrochloride, a GABA(A) receptor agonist, was used in place of picrotoxin. THIP hydrochloride appeared to partially attenuate the decrease in food intake induced by ghrelin at 30 min postinjection. In Experiment 3, the effect of ICV injection of chicken ghrelin on gene expression of glutamate decarboxylase (GAD)(1) and GAD(2), GABA synthesis enzymes in the brain stem including hypothalamus, was investigated. The ICV injection of chicken ghrelin significantly reduced GAD(2) gene expression. These findings suggest that ghrelin may decrease food intake in neonatal chicks by reducing GABA synthesis and thereby GABA release within brain feeding centers.
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ABSTRACT: The present study was designed to examine the effects of intracerebroventricular (ICV) injection of Dopamine (10, 20 and 40 nmol), L-DOPA (dopamine precursor; 62.5, 125 and 250 nmol), 6-OHDA (dopamine inhibitor; 75, 150 and 300 nmol), SCH 23390 (D1 antagonist; 2.5, 5 and 10 nmol), AMI-193 (D2 antagonist; 2.5, 5 and 10 nmol), NGB2904 (D3 antagonist; 3.2, 6.4 and 12.8 nmol), L-741 T742 (D4 antagonist; 1.5, 3 and 6 nmol) on food intake in FD3 chickens. At following, birds were ICV injected using 8-OH-DPAT (5-HT1A agonist; 15.25 nmol) and SB242084 (5-HT2C antagonist; 1.5 μg) prior dopamine (40 nmol) injection. Cumulative food intake was determined until 3 h post-injection. According to the results, dopamine significantly decreased food intake in chickens (p < 0.05). The inhibitory effect of dopamine on food intake was decreased by SCH 23390 pretreatment (P < 0.05), but AMI-193, NGB2904 and L-741, 742 had no effect on food intake induced by dopamine. In addition, hypophagic effect of dopamine was attenuated by SB242084 (P < 0.05), but 8-OH-DPAT had no effect. These results suggest that dopamine decrease food intake via D1 receptor and there is an interaction between dopaminergic and serotonergic systems via 5-HT2C receptor in chickens.Veterinary Research Communications 10/2013; · 1.08 Impact Factor
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ABSTRACT: It has been reported that serotonin can modulate glutamate and GABA release in central nervous system (CNS). The present study was designed to examine the role of glutamatergic and GABAergic systems on serotonin- induced feeding behavior in chickens. In Experiment 1 intracerebroventricular (ICV) injection of MK- 801(NMDA receptor antagonist, 15 nmol) performed followed by serotonin (10 μg). In experiments 2, 3, 4, 5, 6 and 7 prior to serotonin injection, chickens received CNQX (AMPA/kainate receptor antagonist, 390 nmol), AIDA (mGluR1 antagonist, 2 nmol), LY341495 (mGluR2 antagonist, 150 nmol), UBP1112 (mGluR3 antagonist, 2 nmol), picrotoxin (GABA A receptor antagonist, 0.5 μg), CGP54626 (GABAB receptor antagonist, 20 ng) respectively. Cumulative food intake was determined at 3 h post injection. The results of this study showed that the hypophagic effect of serotonin was significantly attenuated by pretreatment with MK- 801 and CNQX (p < 0.05) but AIDA, LY341495 and UBP1112 had no effect (p > 0.05). Also, the inhibitory effect of serotonin on food intake was amplified by picrotoxin (p < 0.05) while CGP54626 had no effect (p > 0.05). These results suggest that serotonin as a modulator probably interacts with glutamatergic (via NMDA and AMPA/Kainate receptors) and GABAergic (via GABAA receptor) systems on feeding behavior in chicken.Veterinary Research Communications 09/2013; · 1.08 Impact Factor
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ABSTRACT: AIMS: We have previously demonstrated that absence of functional GABA B receptors (GABABRs) disturbs glucose homeostasis in GABAB1KO mice. The aim of this work was to extend our studies of these alterations in GABAB1KO mice and investigate the sexual differences therein. MAIN METHODS: Male and female, GABAB1KO and WT mice were used. Glucose and insulin tolerance tests (GTT and ITT), and insulin and glucagon secretion tests (IST and GST) were performed. Blood glucose, serum insulin and hyperglycemic hormones were determined, and HOMA-IR calculated. Skeletal muscle insulin receptor β subunit (IRβ), insulin receptor substrates 1/2 (IRS1, IRS2) and hexokinase-II levels were determined by Western Blot. Skeletal muscle insulin sensitivity was assessed by in vivo insulin-induced Akt phosphorylation (Western Blot). Food intake and hypothalamic NPY mRNA expression (by qPCR) were also evaluated. KEY FINDINGS: Fasted insulin and HOMA-IR were augmented in GABAB1KO males, with no alterations in females. Areas under the curve (AUC) for GTT and ITT were increased in GABAB1KO mice of both genders, indicating compromised insulin sensitivity. No genotype differences were observed in IST, GST or in IRβ, IRS1, IRS2 and hexokinase-II expression. Akt activation was severely impaired in GABAB1KO males while no alterations were observed in females. GABAB1KO mice showed increased food intake and NPY expression. SIGNIFICANCE: Glucose metabolism and energy balance disruptions were more pronounced in GABAB1KO males, which develop peripheral insulin resistance probably due to augmented insulin secretion. Metabolic alterations in females were milder and possibly due to previously described reproductive disorders, such as persistent estrus.Life sciences 11/2012; · 2.56 Impact Factor