Hypothalamic CRF1 receptor mechanisms are not sufficient to account for binge-like palatable food consumption in female rats.

Objective: The present study evaluated the effect of systemic injection of the CRF1 receptor antagonist R121919, the corticosterone synthesis inhibitor metyrapone and central amygdala (CeA) injections of the nonselective CRF antagonist D-Phe-CRF in rats in which binge eating was evoked by stress and cycles of food restriction.

Method: Female rats were subjected or not to repeated cycles of regular chow food restriction/ad libitum feeding during which they were also given limited access (2 h) to palatable food. On the test day, rats were either exposed or not to the sight of the palatable food for 15 min without allowing access, before assessing food consumption.

Role of bed nucleus of the stria terminalis corticotrophin-releasing factor receptors in frustration stress-induced binge-like palatable food consumption in female rats with a history of food restriction.

We developed recently a binge-eating model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after 15 min exposure to the sight of the palatable food. This "frustration stress" manipulation also activates the hypothalamic-pituitary-adrenal stress axis. Here, we determined the role of the stress neurohormone corticotropin-releasing factor (CRF) in stress-induced binge eating in our model.

Caloric restriction increases the sensitivity to the hyperphagic effect of nociceptin/orphanin FQ limiting its ability to reduce binge eating in female rats.

Rationale: Nociceptin/orphanin FQ (N/OFQ) is a functional antagonist of corticotrophin-releasing factor, the main mediator of the stress response. Stress represents a key determinant of binge eating (BE) for highly palatable food (HPF).

Objectives: In relation to the antistress properties of N/OFQ, we evaluated its effect on BE.

Commercially available lipid formulations of amphotericin b: are they bioequivalent and therapeutically equivalent?

Amphotericin B is a polyene macrolide derived from Streptomyces nodosus. Introduced into therapy in 1957, for decades amphotericin B has been the "gold standard" for fighting systemic fungal infections. In order to facilitate its systemic use, much attention has been paid to the development of pharmaceutical forms that could reduce its toxicity, especially for the kidney.

Reduced limbic metabolism and fronto-cortical volume in rats vulnerable to alcohol addiction.

Alcohol abuse is associated with long-term reductions in fronto-cortical volume and limbic metabolism. However, an unanswered question in alcohol research is whether these alterations are the sole consequence of chronic alcohol use, or contain heritable contributions reflecting biological propensity toward ethanol addiction. Animal models of genetic predisposition to alcohol dependence can be used to investigate the role of inborn brain abnormalities in the aetiology of alcoholism.

Effect of Hypericum perforatum Extract in an Experimental Model of Binge Eating in Female Rats.

Purpose. The present study evaluated the effect of Hypericum perforatum dry extract in an experimental model of binge eating (BE). Methods.

A2A adenosine receptor agonists reduce both high-palatability and low-palatability food intake in female rats.

The present study examined the effect of two A(2A) adenosine receptor (AR) agonists, CGS 21680 and VT 7, on high-palatability food (HPF) intake in a model of binge eating in sated rats and on low-palatability food (LPF) intake in food-deprived rats. Binge eating was induced in female rats by three 8-day cycles of food restriction/refeeding, followed by acute stress. Two groups of rats were used: NR+NS rats normally fed and not stressed and R+S rats exposed to cycles of food restriction/refeeding and then stressed.

Role of orexin-1 receptor mechanisms on compulsive food consumption in a model of binge eating in female rats.

Orexins (OX) and their receptors (OXR) modulate feeding, arousal, stress, and drug abuse. Neural systems that motivate and reinforce drug abuse may also underlie compulsive food seeking and intake. Therefore, the effects of GSK1059865 (5-bromo-N-[(2S,5S)-1-(3-fluoro-2-methoxybenzoyl)-5-methylpiperidin-2-yl]methyl-pyridin-2-amine), a selective OX(1)R antagonist, JNJ-10397049 (N-(2,4-dibromophenyl)-N'-[(4S,5S)-2,2-dimethyl-4-phenyl-1,3-dioxan-5-yl]urea), a selective OX(2)R antagonist, and SB-649868 (N-[((2S)-1-{[5-(4-fluorophenyl)-2-methyl-1,3-thiazol-4-yl]carbonyl}-2-piperidinyl)methyl]-1-benzofuran-4-carboxamide), a dual OX(1)/OX(2)R antagonist were evaluated in a binge eating (BE) model in female rats.

Role of nociceptin/orphanin FQ receptors in the decrease of mucosal mast cells caused by acute stress in the rat colon.

Aims: Mucosal mast cells (MMC) are mediators of the stress responses in the gastrointestinal tract. We examined the effect of acute cold-restraint stress and of the neuropeptide nociceptin/orphanin FQ (N/OFQ), implicated in the modulation of stress responses, on MMC density in the rat colon.

Main Methods: Stress was induced by restraining the animals into individual cages at 3°C for 3h.

Pregabalin reduces alcohol drinking and relapse to alcohol seeking in the rat.

Rationale: Pregabalin (Lyrica™) is a structural analogue of γ-aminobutyric acid (GABA) approved by FDA for partial epilepsy, neuropathic pain and recently generalized anxiety disorder. While the exact cellular mechanism of action of pregabalin is still unclear, evidence from several studies suggests that it reduces excitatory neurotransmitter release and postsynaptic excitability.

Objectives: Based on these mechanisms we sought interesting to evaluate the effect of pregabalin on alcohol-abuse-related behaviours.

Effects of A₂A adenosine receptor blockade or stimulation on alcohol intake in alcohol-preferring rats.

Rationale: A(2A) adenosine receptors (A(2A)ARs) have been proposed to be involved in drug addiction; however, preclinical studies about the effects of A(2A)AR ligands on alcohol consumption have provided inconsistent results.

Objectives: The present study evaluated the effect of intraperitoneal injections of the A(2A)AR antagonist ANR 94, and the A(2A)AR agonists CGS 21680 and VT 7 on voluntary drinking and operant self-administration of 10% ethanol in Marchigian Sardinian alcohol-preferring (msP) rats.

Results: Voluntary ethanol drinking was increased by ANR 94 in acute and subchronic experiments, while it was reduced by A(2A)AR agonists.

Gender differences in Nociceptin/Orphanin FQ-induced food intake in strains derived from rats prone (WOKW) and resistant (Dark Agouti) to metabolic syndrome: a possible involvement of the cocaine- and amphetamine-regulated transcript system.

Our previous study found that when injected with Nociceptin/Orphanin FQ (N/OFQ) into the brain, male Dark Agouti (DA) rats, which are resistant to metabolic syndrome, have greater hyperphagia than male Wistar Ottawa Karlsburg W (WOKW) animals, which are prone to this disease. We attributed this difference to the fact that these two strains have different cocaine-amphetamine regulated transcript peptide (Cart) gene sequences and expression. In order to address this hypothesis, the present work focused on sex differences and analyzed not only male but also female N/OFQ-induced (0.

Activation of nuclear PPARγ receptors by the antidiabetic agent pioglitazone suppresses alcohol drinking and relapse to alcohol seeking.

Background: Pioglitazone and rosiglitazone belong to the class of thiazolidinediones (TZDs). They were first developed as antioxidants and then approved for the clinical treatment of insulin resistance and Type 2 diabetes. TZDs bind with high affinity and activate peroxisome proliferator-activated receptor-gamma (PPARγ) receptors, which in the brain are expressed both in neurons and in glia.

Long-term peripheral infusion of nociceptin/orphanin FQ promotes hyperplasia, activation and migration of mucosal mast cells in the rat gastric fundus.

The endogenous neuropeptide nociceptin/orphanin FQ (N/OFQ) modulates behavioral and gastrointestinal responses to stress. Mucosal mast cells (MMCs) are primary mediators of stress-related responses in the gastrointestinal tract. We investigated the influence of N/OFQ and of the N/OFQ peptide (NOP) receptor antagonist, UFP-101, on MMCs in the rat gastric fundus.

Activation of brain NOP receptors attenuates acute and protracted alcohol withdrawal symptoms in the rat.

Background: Alcohol withdrawal refers to a cluster of symptoms that may occur from suddenly ceasing the use of alcohol after chronic or prolonged ingestion. These symptoms make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. In previous studies, we demonstrated that treatment with Nociceptin/orphanin FQ (N/OFQ) significantly reduces alcohol consumption and attenuates alcohol-seeking behavior induced by environmental conditioning factors or by stress in rats.

Neuropeptide S facilitates cue-induced relapse to cocaine seeking through activation of the hypothalamic hypocretin system.

Drug addiction is a chronic relapsing disorder characterized by compulsive drug seeking and use. Environmental conditioning factors are among the major determinants of relapse in abstinent cocaine users. Here we describe a role of the neuropeptide S (NPS) system in regulating relapse.

Effect of salidroside, active principle of Rhodiola rosea extract, on binge eating.

Stress is a key determinant of binge eating (BE). Since Rhodiola rosea is known to modulate stress responses, its effect in a model of BE was investigated. BE for highly palatable food (HPF) was evoked in female rats by three 8-day cycles of food restriction/re-feeding (for 4days 66% of the usual chow intake; for 4days food ad libitum) and acute stress on the test day (day 25).

UFP-112 a potent and long-lasting agonist selective for the Nociceptin/Orphanin FQ receptor.

Nociceptin/orphanin FQ (N/OFQ) controls several biological functions via selective activation of the N/OFQ peptide receptor (NOP). [(pF)Phe(4) Aib(7) Arg(14) Lys(15) ]N/OFQ-NH(2) (UFP-112) is an NOP receptor ligand designed using a combination of several chemical modifications in the same peptide sequence that increase NOP receptor affinity/potency and/or reduce susceptibility to enzymatic degradation. In the present review article, we summarize data from the literature and present original findings on the in vitro and in vivo pharmacological features of UFP-112.

Central nociceptin/orphanin FQ system elevates food consumption by both increasing energy intake and reducing aversive responsiveness.

Nociceptin/orphanin FQ (N/OFQ), the nociceptin opioid peptide (NOP) receptor ligand, increases feeding when injected centrally. Initial data suggest that N/OFQ blocks the development of a conditioned taste aversion (CTA). The current project further characterized the involvement of N/OFQ in the regulation of hunger vs.

Peripheral infusion of nociceptin/orphanin FQ influences the response of rat gastric and colonic mucosa to repeated stress.

The 17-amino acid peptide nociceptin/orphanin FQ (N/OFQ) plays a role in the regulation of stress responses and of emotional disorders. The objective of this study is to evaluate whether long-term peripheral N/OFQ could dose- and time-dependently influence the responses to repeated cold-restraint stress on the rat gastric and colonic mucosa. Rats were exposed to cold-restraint stress for 3h per day for 1, 2 and 3 consecutive days.

Stress-related neuropeptides and alcoholism: CRH, NPY, and beyond.

This article summarizes the proceedings of a symposium held at the conference on "Alcoholism and Stress: A Framework for Future Treatment Strategies" in Volterra, Italy, May 6-9, 2008. Chaired by Markus Heilig and Roberto Ciccocioppo, this symposium offered a forum for the presentation of recent data linking neuropetidergic neurotransmission to the regulation of different alcohol-related behaviors in animals and in humans. Dr.

The paraventricular nucleus of the hypothalamus is a neuroanatomical substrate for the inhibition of palatable food intake by neuropeptide S.

Neuropeptide S (NPS) is a recently discovered neurotransmitter that binds to its cognate G-protein coupled receptor, NPSR. Previous studies have shown that central administration of this peptide induces anxiolytic-like effects, promotes arousal and inhibits feeding in the same dose range. In the present study, we sought to investigate further the unique physiopharmacological profile of the NPS system by characterizing its effects on palatable food consumption in rats and comparing it with the effect of the classical anxiolytic benzodiazepine midazolam.

Chronic treatment with the selective NOP receptor antagonist [Nphe 1, Arg 14, Lys 15]N/OFQ-NH 2 (UFP-101) reverses the behavioural and biochemical effects of unpredictable chronic mild stress in rats.

Introduction: The present study was designed to assess the antidepressant effects of UFP-101, a selective nociceptin/orphanin FQ peptide (NOP) receptor antagonist, in a validated animal model of depression: the chronic mild stress (CMS).

Materials And Methods And Results: UFP-101 (5, 10 and 20 nmol/rat; i.c.

Pre-exposure to environmental cues predictive of food availability elicits hypothalamic-pituitary-adrenal axis activation and increases operant responding for food in female rats.

The present study was undertaken to develop an animal model exploiting food cue-induced increased motivation to obtain food under operant self-administration conditions. To demonstrate the predictive validity of the model, rimonabant, fluoxetine, sibutramine and topiramate, administered 1 hour before the experiment, were tested. For 5 days, female Wistar rats were trained to self-administer standard 45 mg food pellets in one daily session (30 minutes) under FR1 (fixed ratio 1) schedule of reinforcement.

Persistent increase of alcohol-seeking evoked by neuropeptide S: an effect mediated by the hypothalamic hypocretin system.

The association of ethanol's reinforcing effects with specific environmental stimuli is thought to be a critical factor for relapse risk in alcoholism. This study examined in rats the effects of a newly deorphanized neuropeptide receptor and its cognate ligand, Neuropeptide S (NPS), on ethanol consumption and reinstatement of ethanol-seeking by environmental cues previously associated with ethanol availability. In the self-administration experiments, the stable response rates observed for ethanol reinforcement were not modified by intracerebroventricular (ICV) injection of NPS (1.