The role of 5-HT2c receptor on corticosterone-mediated food intake.

Corticosterone plays an important role in feeding behavior. However, its mechanism remains unclear. Therefore, the present study aimed to investigate the effect of corticosterone on feeding behavior. In this study, cumulative food intake was increased by acute corticosterone administration in a dose-dependent manner. Administration of the 5-HT2c receptor agonist m-chlorophenylpiperazin (mCPP) reversed the effect of corticosterone on food intake. The anorectic effects of mCPP were also blocked by the 5-HT2c receptor antagonist RS102221 in corticosterone-treated mice. Both corticosterone and mCPP increased c-Fos expression in hypothalamic nuclei, but not the nucleus of the solitary tract. RS102221 inhibited c-Fos expression induced by mCPP, but not corticosterone. In addition, mCPP had little effect on TH and POMC levels in the hypothalamus. Furthermore, mCPP antagonized decreasing effect of the leptin produced by corticosterone. Taken together, our findings suggest that 5-HT2c receptors and leptin may be involved in the effects of corticosterone-induced hyperphagia.

Effect of norbinaltorphimine on ∆9-tetrahydrocannabinol (THC)-induced taste avoidance in adolescent and adult Sprague-Dawley rats.

RATIONALE: The aversive effects of ∆(9)-tetrahydrocannabinol (THC) are mediated by activity at the kappa opioid receptor (KOR) as assessed in adult animals; however, no studies have assessed KOR involvement in the aversive effects of THC in adolescents. Given that adolescents have been reported to be insensitive to the aversive effects induced by KOR agonists, a different mechanism might mediate the aversive effects of THC in this age group. OBJECTIVES: The present study was designed to assess the impact of KOR antagonism on the aversive effects of THC in adolescent and adult rats using the conditioned taste avoidance (CTA) procedure. METHODS: Following a single pretreatment injection of norbinaltorphimine (norBNI; 15 mg/kg), CTAs induced by THC (0, 0.56, 1.0, 1.8, and 3.2 mg/kg) were assessed in adolescent (n = 84) and adult (n = 83) Sprague-Dawley rats. RESULTS: The KOR antagonist, norBNI, had weak and inconsistent effects on THC-induced taste avoidance in adolescent rats in that norBNI both attenuated and strengthened taste avoidance dependent on dose and trial. norBNI had limited impact on the final one-bottle avoidance and no effects on the two-bottle preference test. Interestingly, norBNI had no effect on THC-induced taste avoidance in adult rats as well. CONCLUSIONS: That norBNI had no significant effect on THC-induced avoidance in adults, and a minor and inconsistent effect in adolescents demonstrates that the aversive effects of THC are not mediated by KOR activity as assessed by the CTA design in Sprague-Dawley rats.

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Contrasting effects of different cannabinoid receptor ligands on mouse ingestive behaviour.

This study characterized the effects of seven diverse cannabinoid receptor agonists (and one antagonist) on ingestive behaviour in nondeprived adult, male CD1 mice. Microstructural analysis of licking for a range of concentrations of condensed milk (10, 15 and 20%) was carried out following administration of vehicle or: Δ9-tetrahydrocannabinol (Δ9-THC) at 1, 3 or 6 mg/kg; CP55,940 at 10, 30 or 50 µg/kg; Win 55,212-2 at 0.5, 1 or 3 mg/kg; HU-210 at 0.01, 0.03 or 0.1 mg/kg; methanandamide at 1, 3 or 6 mg/kg; arachidonyl-2'-chloroethylamide at 1, 3 or 6 mg/kg and JWH133 at 1, 3 or 6 mg/kg. The cannabinoid receptor antagonist/inverse agonist rimonabant was also tested at 0.3, 1 or 3 mg/kg. Test sessions comprised three 30 s presentations of the milk concentrations separated by 10 s interpresentation intervals. The nonselective CB1 receptor agonists Δ9-THC, CP55,940 and Win 55,212-2 increased the number of licks for condensed milk, primarily by a significant increase in bout number. The potent and nonselective CB1 receptor agonist HU-210 and the selective CB1 receptor agonists methanandamide and arachidonyl-2'-chloroethylamide did not significantly affect licking behaviour but did significantly increase the latency to start licking. The CB1 receptor antagonist rimonabant produced effects that were opposite in direction to those produced by Δ9-THC, CP55,940 and Win 55,212-2. Finally, the selective CB2 receptor agonist JWH133 had no significant effects on behaviour. These data add to reports that cannabinoid agonists can enhance the appetitive aspects of feeding, but they also demonstrate that not all CB1 receptor agonists do this, and therefore the relationship between action at CB1 receptors and appetitive feeding effects is not straightforward.

Intracerebroventricular O-n-octanoylated ghrelin and its splice variant-induced feeding is blocked by insulin, independent of obestatin or CRF receptor, in satiated rats.

OBJECTIVE: The purpose of this study was to investigate the impact of intracerebroventricular (ICV) injection of the two endogenous forms of acyl ghrelin, O-n-octanoylated ghrelin and des-Gln¹4-ghrelin, on feeding behavior, as well as their interactions with insulin, obestatin, and corticotropin-releasing factor receptor (CRF-R) antagonist in the forebrain to influence food intake. METHODS: We examined the food intake in conscious, freely fed rats, which were chronically implanted with ICV catheters. RESULTS: O-n-octanoylated ghrelin and des-Gln¹4-ghrelin (0.1 nmol/rat) were equally potent in stimulating food intake in freely fed rats, up to 8 h after ICV injection (P < 0.05). In contrast, ICV administration of insulin (8 mU/rat), obestatin (2 nmol/rat), and astressin (2 nmol/rat), a specific CRF-R antagonist, did not modify feeding in freely fed rats. Furthermore, pretreatment with ICV insulin (P < 0.01), but not obestatin or astressin, at the abovementioned dose, blocked central acyl-ghrelin-induced hyperphagic effects. CONCLUSION: ICV O-n-octanoylated ghrelin and its splice variant, des-Gln¹4-ghrelin, are equally potent to elicit food intake in freely fed rats, while these feeding-stimulating effects are opposed by insulin, but independent of obestatin and endogenous CRF-R in the forebrain.

Suppression of third ventricular NPY-elicited feeding following medullary reticular formation infusions of muscimol.

The appetitive component of feeding is controlled by forebrain substrates, but the consummatory behaviors of licking, mastication, and swallowing are organized in the brainstem. The target of forebrain appetitive signals is unclear but likely includes regions of the medullary reticular formation (RF). This study was undertaken to determine the necessity of different RF regions for mastication induced by a descending appetitive signal. We measured solid food intake in response to third ventricular (3V) infusions of the orexigenic peptide neuropeptide Y 3-36 in awake, freely moving rats and determined whether focal RF infusions of the GABAA agonist muscimol suppressed eating. RF infusions were centered in either the lateral tegmental field, comprising the intermediate (IRt) and parvocellular (PCRt) RF, or in the nucleus gigantocellularis (Gi). Infusions of NPY 3-36 (5 microg/5 microl) into 3V significantly increased feeding of solid food over a 90-min period compared with the noninfused condition (4.3 g +/- 0.56 vs. 0.57 g +/- 0.57, p < .001). NPY 3-36-induced food intake was suppressed (1.7 g +/- 0.48) by simultaneous infusions of muscimol (0.6 mM/100 nl) into the IRt/PCRt (p < .01). Coincident with the decrease in feeding was a decrease in the amplitude of anterior digastric muscle contractions in response to intraoral sucrose infusions. In contrast, infusions of muscimol into Gi had no discernible effect on food intake or EMG amplitude. These data suggest that the IRt/PCRt is essential for forebrain-initiated mastication, but that the Gi is not a necessary link in this pathway.

The cannabinoid CB1 receptor antagonist SR141716 blocks the orexigenic effects of intrahypothalamic ghrelin.

The paraventricular nucleus (PVN) of the hypothalamus plays a key role in the control of appetite and energy balance. Both ghrelin and cannabinoid receptor agonists increase food intake when administered into this nucleus: this study investigated possible interactions between the two systems in relation to eating. The orexigenic effect of ghrelin (100 pmol) when infused in to the PVN was reversed by a small, systemic dose of the CB(1) cannabinoid receptor antagonist SR141716 (1 mg kg(-1)). This is the first demonstration of a functional relationship between brain ghrelin and endocannabinoid systems, and, although it needs to be further investigated, the effect of ghrelin on food intake when injected into the PVN seems to be mediated by stimulation of cannabinoid release.

Central bombesin inhibits food intake and the orexigenic effect of neuropeptide Y in the neonatal chick.

It is well known that central injection of bombesin (BN) suppresses feeding in mammalian and avian species, but the anorexigenic effect of central BN are still open with special reference to the chick. The dose response (0, 0.1 and 0.5 microg) of intracerebroventricular (ICV) injection of BN was examined in Experiment 1. ICV injection of BN inhibited food intake in a dose-dependent manner. Experiment 2 was done to determine whether BN interacts with the orexigenic effect of neuropeptide Y (NPY) in the neonatal chick. Central administration of NPY (2.5 microg) greatly enhanced food intake, but co-injection of BN (0.5 microg) suppressed food intake. The dose response of NPY (2.5 microg) co-injected with three levels of BN (0, 0.1 and 0.5 microg) was examined in Experiment 3. ICV injection of BN attenuated the hyperphagia by NPY in a dose-related fashion. It is suggested that central BN may interact with NPY for the regulation of feeding in the neonatal chick.

Zinc and nitric oxide synthase inhibitor L-NAME attenuate NPY-induced feeding in mice.

The influences of zinc (Zn) and the nitric oxide synthase (NOS) inhibitor L-NAME on peripheral neuropeptide Y (NPY)-induced feeding in mice were investigated. Male mice received NPY (200 ng/d/mouse subcutaneously) and were separated into four groups based on cotreatments (with or without Zn [0.1 mg/mL]) and with or without L-NAME [0.2 mg/mL]) administered in drinking water for 10 d. A control group that received saline injection was also studied. The results showed that NPY, with or without any studied chemicals, did not affect body weight gain or body fat content. However, the mice that were administered NPY alone had increased energy intakes, higher serum triglyceride and free fatty acid, and lower serum glucose than saline-injected controls. NPY-treated mice that were given Zn and L-NAME cotreatments had compatible results of determined variables in comparison with control mice. This study showed that Zn and L-NAME attenuated NPY-mediated feeding and selected serum variables in mice. However, the mechanisms of the interactions among NPY, Zn and NOS, and their effects on appetite regulation, remain to be elucidated.

Leptin decreases food intake induced by melanin-concentrating hormone (MCH), galanin (GAL) and neuropeptide Y (NPY) in the rat.

Recent evidence suggests that leptin reduces food intake (FI) by acting at the hypothalamic level. Leptin decreases hypothalamic neuropeptide Y (NPY), melanin-concentrating hormone (MCH) and galanin (GAL) gene expression in rats. The purpose of the present study was to test the hypothesis that leptin decreases FI by additionally modulating the action of NPY, MCH or GAL in the hypothalamus. Intracerebroventricular (i.c.v.) administration of NPY, MCH or GAL induced FI in satiated rats. A prior i.c.v. injection of leptin (4 microg) completely prevented the increase of FI either by MCH, GAL or NPY. These results suggest that modulation of post-synaptic actions of MCH, GAL and NPY is one of the mechanisms of leptin signaling in the hypothalamus.

Interaction of the hypothalamic paraventricular nucleus and central nucleus of the amygdala in naloxone blockade of neuropeptide Y-induced feeding revealed by c-fos expression.

Neuropeptide Y (NPY) is a powerful inducer of food intake with a key site of action in the paraventricular nucleus (PVN) of the hypothalamus. An effective method for inhibiting the effects of NPY is pretreatment with the opioid antagonists naloxone or naltrexone. In the present study, we used immunohistochemistry for cFos as a marker of neuronal activity to map the effects of PVN-injected NPY and blockade of these effects by peripheral injection of naloxone. Injection of NPY into the PVN resulted in an increase in food intake that was blocked by peripheral administration of naloxone. PVN NPY also resulted in increased cFos immunoreactivity (cFos-IR) in the PVN independent of food intake, and although peripheral naloxone inhibited NPY-induced feeding, it did not alter cFos-IR in the PVN. cFos-IR in the central nucleus of the amygdala (CNA) increased in response to both NPY and naloxone. Furthermore, the response to NPY and naloxone was additive, suggesting that peripheral naloxone and PVN NPY activate different neuronal populations in the CNA. Three other brain regions, the nucleus of the solitary tract, the ventrolateral medulla, and the supraoptic nucleus, all showed increases in cFos-IR in this study, but these changes came only as a result of increased food intake after PVN-injected NPY. The current data suggest that the CNA is a site important for the integration of the NPY and opioid systems.