The interaction of central nitrergic and GABAergic systems on food intake in neonatal layer-type chicks.

Most physiological behaviors such as food intake are controlled by the hypothalamus and its nuclei. It has been demonstrated that injection of the paraventricular nucleus of the hypothalamus with nitric oxide (NO) donors elicited changes in the concentration of some amino acids, including GABA. Also, central nitrergic and GABAergic systems are known to provide inputs to the paraventricular nucleus and are involved in food intake control. Therefore, the present study examines the probable interaction of central nitrergic and GABAergic systems on food intake in neonatal layer-type chicks. The results of this study showed that intracerebroventricular (ICV) injection of L-arginine (400 and 800 nmol), as a NO donor, significantly decreased food intake (P < 0.001), but ICV injection of Nω-Nitro-L-arginine methyl ester (L-NAME) (200 and 400 nmol), a NO synthesis inhibitor, increased food intake (P < 0.001). In addition, the orexigenic effect of gaboxadol (0.2 µg), a GABAA agonist, was significantly attenuated in ICV co-injection of L-arginine (200 nmol) and gaboxadol (0.2 µg) (P < 0.001), but it was significantly amplified in ICV co-injection of L-NAME (100 nmol) and gaboxadol (0.2 µg) (P < 0.001). On the other hand, the orexigenic effect of baclofen (0.2 µg), a GABAB agonist, did not change in ICV co-injection of L-arginine (200 nmol) or L-NAME (100 nmol) with baclofen (0.2 µg) (P > 0.05). Also, the hypophagic effect of L-arginine (800 nmol) was significantly amplified in ICV co-injection of picrotoxin (0.5 µg), a GABAA antagonist, or CGP54626 (21 ng), a GABAB antagonist, with L-arginine (800 nmol) (P < 0.001). These results probably suggest an interaction of central nitrergic and GABAergic systems on food intake in neonatal layer-type chicks and GABAA receptors play a major role in this interaction.

Chronic central nervous system MC3/4R blockade attenuates hypertension induced by nitric oxide synthase inhibition but not by angiotensin II infusion.

We examined whether central melanocortin 3 and 4 receptor (MC3/4R) blockade attenuates the blood pressure (BP) responses to chronic L-NAME or angiotensin II (Ang II) infusion in Sprague-Dawley rats implanted with telemetry transmitters, venous catheters, and intracerebroventricular cannula into the lateral ventricle. After 5 days of control measurements, L-NAME (10 µg/kg/min IV, groups 1 and 2) or Ang II (10 ng/kg/min IV, groups 3 and 4) were infused for 24 days, and starting on day 7 of L-NAME or Ang II infusion, the MC3/4R antagonist SHU-9119 (24 nmol/d, n=6/group; groups 1 and 3) or vehicle (saline 0.5 µL/h, n=6/group; groups 2 and 4) was infused intracerebroventricularly for 10 days. A control normotensive group also received SHU-9119 for 10 days (n=5). L-NAME and Ang II increased BP by 40±3 and 56±5 mm Hg, respectively, although heart rate was slightly reduced. MC3/4R blockade doubled food intake and reduced heart rate (≈40 to ≈50 bpm) in all groups. MC3/4R blockade caused only a small reduction in BP in normotensive group (4 mm Hg) and no change in rats receiving Ang II, although markedly reducing BP by 21±4 mm Hg in L-NAME-treated rats. After SHU-9119 infusion was stopped, food intake, heart rate, and BP gradually returned to values observed before SHU-9119 infusion was started. Ganglionic blockade at the end of L-NAME or Ang II infusion caused similar BP reduction in both groups. These results suggest that the brain MC3/4R contributes, at least in part, to the hypertension induced by chronic L-NAME infusion but not by Ang II.

The effect of serotonergic system on nociceptin/orphanin FQ induced food intake in chicken.

The present study was designed to examine the effects of intracerebroventricular injection of para-chlorophenylalanine (PCPA) (cerebral serotonin depletive), fluoxetine (selective serotonin reuptake inhibitor), 8-OH-DPAT (5-HT1A autoreceptor agonist) and SB 242084 (5-HT2c receptor antagonist) on nociceptin/orphanin FQ (N/OFQ) induced feeding response in chickens. A guide cannula was surgically implanted into the lateral ventricle of chickens. Before the experiments, 3-h fasting periods had been given to all experimental birds. In experiment 1, chickens were injected with PCPA (1.5 µg) followed by an N/OFQ injection (16 nmol) intracerebroventricularly. In experiment 2, birds received fluoxetine (10 µg) prior to the injection of N/OFQ. In experiment 3, chickens were administered with N/OFQ after the 8-OH-DPAT administration (15.25 nmol). In experiment 4, birds were injected with SB 242084 (1.5 µg) followed by an N/OFQ injection. Cumulative food intake was measured at 3 h post injection. The results of this study show that N/OFQ increases food intake in broiler cockerels (P < 0.05) and that this effect is amplified by pretreatment with PCPA and SB 242084 in an additive manner (P < 0.05). The effect of N/OFQ is not changed by pretreatment with 8-OH-DPAT (P > 0.05). Furthermore, the stimulatory effect of N/OFQ on food intake was significantly attenuated by pretreatment with fluoxetine. These results suggest that N/OFQ induced hyperphagia is mediated by serotonergic mechanisms, and possibly imply an interaction between N/OFQ and the serotonergic system (via 5-HT2C receptors) on food intake in chickens.

Intracerebroventricular injection of ghrelin produces hypophagia through central serotonergic mechanisms in chicken.

It has been stated that central injection of ghrelin is acting as an anorexigenic peptide in chicken. Ghrelin activity was studied through some neuronal pathways. The present study was designed in 4 experiments to examine the hypophagic response of ghrelin through the central serotonergic system in chicken. The guide cannula was surgically implanted in the right lateral ventricle of the chickens. In experiment 1, intacerebroventricular injection with PCPA (1.5 mg) performed followed by ghrelin (0.6 nmol). In experiments 2, 3 and 4 prior to ghrelin injection, chickens received fluoxetine (10 µg), 8-OH-DPAT (15.25 nmol), SB242084 (1.5 µg) respectively via guide cannula intacerebroventricularly. Cumulative food intake was determined at 3 h post injection. The results of this study showed that flouxetine pretreatment significantly amplified ghrelin hypophagia in chicken (p < 0.05). The hypophagic effect of ghrelin was attenuated by pretreatment with PCPA and SB242084 (p < 0.05) but 8-OH-DPAT had no effect. These results suggest that hypophagic effect of ghrelin probably is mediated by serotonergic mechanisms via 5-HT(2C) receptor.

The effect of melanocortin (Mc3 and Mc4) antagonists on serotonin-induced food and water intake of broiler cockerels.

The current study was designed to examine the effects of intracerebroventricular injections of SHU9119 [a nonselective melanocortin receptor (McR) antagonist] and MCL0020 (a selective McR antagonist) on the serotonin-induced eating and drinking responses of broiler cockerels deprived of food for 24 h (FD24). For Experiment 1, the chickens were intracerebroventricularly injected with 2.5, 5, and 10 µg serotonin. In Experiment 2, the chickens received 2 nmol SHU9119 before being injected with 10 µg serotonin. For Experiment 3, the chickens were given 10 µg serotonin after receiving 2 nmol MCL0020, and the level of food and water intake was determined 3 h post-injection. Results of this study showed that serotonin decreased food intake but increased water intake among the FD24 broiler cockerels and that these effects occurred in a dose-dependent manner. The inhibitory effect of serotonin on food intake was significantly attenuated by pretreatment with SHU9119 and MCL0020. However, the stimulatory effect of serotonin on water intake was not altered by this pretreatment. These results suggest that serotonin hypophagia and hyperdipsia were mediated by different mechanisms in the central nervous system, and that serotonin required downstream activation of McRs to promote hypophagia but not hyperdipsia in the FD24 chickens.