Effects Of Neuropeptide Y Research Articles

Evidence for a potential role of neuropeptide Y in ovine corpus luteum function

Neuropeptide Y (NPY) is a neurohormone that is typically associated with food intake, but it has also been reported to affect the production of progesterone from luteal tissue in vitro. However, NPY has not been previously immunolocalized in the ovine ovary or in the corpus luteum (CL) of any species, and the effects of this neurohormone on luteal function in vivo are not known. Thus, we performed fluorescent immunohistochemistry (IHC) to localize NPY in the ovine ovary and used avidin-biotin immunocytochemistry (ICC) to further define the intracellular localization within follicles and the CL. We then infused NPY directly into the arterial supply of the autotransplanted ovaries of sheep to determine the in vivo effect of exogenous NPY on ovarian blood flow and on the luteal secretion rate of progesterone and oxytocin. Immunohistochemistry revealed that the NPY antigen was localized to cells within the follicles and CL, in the nerve fibers of the ovarian stroma, and in the vessels of the ovarian hilus. In the follicle, the NPY antigen was localized to nerves and vessels within the theca interna layer, and strong staining was observed in the granulosal cells of antral follicles. In the CL, NPY was localized in large luteal cells and in the vascular pericytes and/or endothelial cells of blood vessels, found dispersed throughout the gland and within the luteal capsule. In vivo incremental infusions of NPY at 1, 10, 100, and 1,000 ng/min, each for a 30-min period, into the arterial supply of the transplanted ovary of sheep bearing a CL 11 d of age increased ( P ≤ 0.05) ovarian blood flow. The intra-arterial infusions of NPY also increased ( P ≤ 0.05) in a dose-dependent manner the secretion rate of oxytocin, which was positively correlated ( P ≤ 0.05) with the observed increase in ovarian blood flow. The infusions of NPY had a minimal effect on the secretion rate of progesterone, and similar intra-arterial infusions of NPY into sheep with ovarian transplants bearing a CL over 30 d of age had no significant effect on ovarian blood flow or on the secretion rate of progesterone. These results suggest that NPY acts on the luteal vascular system and the large luteal cells to rapidly stimulate blood flow and the secretion of oxytocin, respectively, which collectively implies a putative role for NPY during the process of luteolysis when increasing amounts of oxytocin are secreted from the ovine CL in response to uterine pulses of prostaglandin F2α.

Site-specific attenuation of food intake but not the latency to eat after hypothalamic injections of neuropeptide Y in dehydrated-anorexic rats

Anorexia that accompanies cellular dehydration in rats (DE-anorexia) offers a relatively simple model for investigating the functional organization of neural mechanisms that can suppress feeding during dehydration. Previous studies strongly suggest that the inputs that drive ingestive behavior control neurons in the paraventricular nucleus of the hypothalamus (PVH) and lateral hypothalamic area (LHA) remain active during DE-anorexia. Here we examine whether these two regions retain their sensitivity to neuropeptide Y (NPY). NPY is an important component in two major feeding-related inputs from the arcuate nucleus and the hindbrain. We found that intake responses to NPY injections in the LHA and PVH were suppressed in DE-anorexia, but the PVH remained less sensitive to the effects of NPY than the LHA in DE-anorexic animals. Indeed the higher dose of NPY (238 pmol) completely overcame shorter periods of DE-anorexia when injected into the LHA but not the PVH. However, the latency to eat after NPY injections remained unchanged from control animals, regardless of NPY dose, injection location, or intensity of anorexia. Furthermore, the onset and size of the strong and rapidly induced compensatory feeding that follows the return of water to DE-anorexic animals was also unaffected by any NPY injections. These data support the hypothesis that DE-anorexia develops as a consequence of the premature termination of regularly initiated meals, which perhaps involves processes that alter the sensitivity of satiety mechanisms downstream to the PVH and LHA.

Neuropeptide Y modulates steroid production of human adrenal H295R cells through Y1 receptors

Neuropeptide Y (NPY) is abundantly expressed in the nervous system and acts on target cells through NPY receptors. The human adrenal cortex and adrenal tumors express NPY receptor subtype Y1, but its function is unknown. We studied Y1-mediated signaling, steroidogenesis and cell proliferation in human adrenal NCI-H295R cells. Radioactive ligand binding studies showed that H295R cells express Y1 receptor specifically. NPY treatment of H295R cells stimulated the MEK/ERK1/2 pathway, confirming that H295R cells express functional Y1 receptors. Studies of the effect of NPY and related peptide PYY on adrenal steroidogenesis revealed a decrease in 11-deoxycortisol production. RIA measurements of cortisol from cell culture medium confirmed this finding. Co-treatment with the Y1 antagonist BIBP2336 reversed the inhibitory effect of NPY on cortisol production proving specificity of this effect. At mRNA level, NPY decreased HSD3B2 and CYP21A2 expression. However NPY revealed no effect on cell proliferation. Our data show that NPY can directly regulate human adrenal cortisol production.

The effects of neuropeptide Y on skeletal muscle contractile properties in streptozotocin diabetic rats

Diabetes induces changes in the structural, biochemical, electrical, and contractile properties of skeletal muscles. Neuropeptide Y (NPY) administered locally can induce angiogenesis in a rat ischemic limb model and restore the contractile function of the ischemic muscle. The effects of NPY on the contractile characteristics of limb skeletal muscles were examined in streptozotocin-induced diabetic rats. Rats were treated with sham pellets (control groups) or NPY-containing pellets (1 mg of NPY/pellet, 14 days releasing time) administered locally to the rat hind limb 2 months after induction of diabetes. Contractile properties and fatigability of the slow-twitch soleus and fast-twitch gastrocnemius medials muscle were compared in control (sham), control NPY, diabetic (sham), and diabetic NPY groups. In order to induce fatigue trains of repetitive tetanic stimulation were used (600 ms/1 s simulation-rest cycle per train, 112 trains at an 85-Hz fusion frequency). Two months of untreated diabetes significantly prolonged soleus contraction and slowed its relaxation, but had minimal effects on soleus tension. NPY ameliorated the diabetic effects on soleus speed-related contractile properties, restoring its contraction and relaxation times. Diabetes significantly reduced gastrocnemius medials tetanic tension, leaving its contractile characteristics mostly unaffected. NPY partially restored gastrocnemius tetanic tension production capacity. Diabetes significantly increased fatigability of both muscles, which was partially restored by NPY, as evidenced by restored endurance of soleus muscle. The results suggest that NPY administered locally tends to normalize muscle performance and improve fatigue resistance of skeletal muscles in streptozotocin diabetes. Further examination is needed to establish the mechanisms of local NPY action on muscle contractile properties in streptozotocin-induced diabetes.

Fear-reducing effects of intra-amygdala neuropeptide Y infusion in animal models of conditioned fear: an NPY Y1 receptor independent effect

Neuropeptide Y (NPY) and its receptors are densely localized in brain regions involved in the mediation and modulation of fear, including the amygdala. Several studies showed that central NPY is involved in the modulation of fear and anxiety. In the present study, we investigated (1) whether intra-amygdala injections of NPY affect the expression of conditioned fear and (2) whether NPY Y1 receptors (Y1R) mediates the effects of these intra-amygdaloid NPY injections. Intra-amygdala NPY injections robustly decreased the expression of conditioned fear measured by conditioned freezing and fear-potentiated startle. These NPY effects were not mimicked by intra-amygdala injections of the Y1R agonists Y-28 or Y-36, and co-infusion of the Y1R antagonist BIBO 3304 did not block the NPY effects. Furthermore, we tested Y1R-deficient mice in conditioned freezing and found no differences between wild type and mutant littermates. Finally, we injected NPY into the amygdala of Y1R-deficient mice. Y1R deficiency had no effect on the fear-reducing effects of intra-amygdala NPY. These data show an important role of the transmitter NPY within the amygdala for the expression of conditioned fear. Y1R do not appear to be involved in the mediation of the observed intra-amygdala NPY effects suggesting that these effects are mediated via other NPY receptors.

Possible common central pathway for resistin and insulin in regulating food intake

Adipose tissue has been the object of intense research in the field of obesity and diabetes diseases in the last decade. Examination of adipocyte-secreted peptides led to the identification of a unique polypeptide, resistin (RSTN), which has been suggested as a link between obesity and diabetes. RSTN plays a clearly documented role in blocking insulin (INS)-induced hypoglycaemia. As brain injection of INS affects feeding behaviour, we studied the possible interaction between INS and RSTN in food-deprived rats, measuring effects on food intake. In addition, we examined how RSTN might affect neuropeptide Y (NPY)-induced feeding, as studies have shown that rat RSTN can interfere with the NPY system. Overnight food-deprived rats were injected into the third brain ventricle (3V) with either INS (10 or 20 mUI), RSTN (0.1-0.4 nmol/rat), or saline before access to food. Another group of rats was injected into the 3V with RSTN alone, NPY alone or RSTN plus NPY. Their food intake and body weight were measured. Our results confirm the hypophagic effect of RSTN on food deprivation-induced food intake, and more importantly, show that RSTN neither potentiates nor blocks the effects of INS on food intake, but does reduce the hyperphagic effect of NPY. The observation that RSTN does not modify feeding INS-induced hypophagia, but does influence NPY-induced feeding, points to the possibility that RSTN may be involved in control of food intake through an NPY-ergic mechanism as INS.

Neuropeptide Y and neurovascular control in skeletal muscle and skin

Neuropeptide Y (NPY) is a ubiquitous peptide with multiple effects on energy metabolism, reproduction, neurogenesis, and emotion. In addition, NPY is an important sympathetic neurotransmitter involved in neurovascular regulation. Although early studies suggested that the vasoactive effects of NPY were limited to periods of high stress, there is growing evidence for the involvement of NPY on baseline vasomotor tone and sympathetically evoked vasoconstriction in vivo in both skeletal muscle and the cutaneous circulation. In Sprague-Dawley rat skeletal muscle, Y(1)-receptor activation appears to play an important role in the regulation of basal vascular conductance, and this effect is similar in magnitude to the alpha(1)-receptor contribution. Furthermore, under baseline conditions, agonist and receptor-based mechanisms for Y(1)-receptor-dependent control of vascular conductance in skeletal muscle are greater in male than female rats. In skin, there is Y(1)-receptor-mediated vasoconstriction during whole body, but not local, cooling. As with the NPY system in muscle, this neural effect in skin differs between males and females and in addition, declines with aging. Intriguingly, skin vasodilation to local heating also requires NPY and is currently thought to be acting via a nitric oxide pathway. These studies are establishing further interest in the role of NPY as an important vasoactive agent in muscle and skin, adding to the complexity of neurovascular regulation in these tissues. In this review, we focus on the role of NPY on baseline vasomotor tone in skeletal muscle and skin and how NPY modulates vasomotor tone in response to stress, with the aim of compiling what is currently known, while highlighting some of the more pertinent questions yet to be answered.

Cardiovascular autonomic function assessed by autonomic function tests and serum autonomic neuropeptides in Egyptian children and adolescents with rheumatic diseases

Cardiovascular autonomic neuropathy (CAN) in patients with rheumatic diseases may result in sudden death, possibly from arrhythmia and myocardial infarction due to its frequent association with microvascular disease. Autonomic dysfunction may contribute to initiation and perpetuation of rheumatic diseases. Thus, we aimed to assess cardiovascular autonomic function in lupus and juvenile idiopathic arthritis (JIA) patients. Assessment of cardiovascular autonomic function was done in 20 lupus and 20 JIA patients, aged 8-16 years, by five non-invasive autonomic function tests (AFTs) and serum levels of neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP), as indicators of sympathetic and parasympathetic functions, respectively, in comparison with 40 matched healthy control subjects. Clinical evidence of CAN was found in 65 and 40% of lupus and JIA patients, respectively, and in none of healthy controls. Lupus and JIA patients had significantly lower serum NPY and VIP than controls (P < 0.001). The five AFTs score had significant negative correlations to NPY and VIP (P < 0.001). Patients with CAN had significantly lower serum NPY and VIP than patients without (P < 0.001). Clinical evidence of CAN was found in 41.7 and 14.3% of asymptomatic lupus and JIA patients, respectively. There was significant positive association between CAN and important disease manifestations, including activity, in these patients. CAN is common in lupus and JIA patients, even in absence of relevant symptoms. Thus, assessments of cardiac autonomic function, by AFTs and serum autonomic neuropeptides (NPY and VIP), and the therapeutic effects of NPY and VIP are recommended in these patients.

NPY revealed as a critical modulator of osteoblast function in vitro: New insights into the role of Y1 and Y2 receptors

Neuropeptide Y (NPY) has recently emerged as a potential regulator of bone homeostasis. However, the relevance of NPY's role in osteoblast activity and the biological functions involving NPY receptors in bone homeostasis remain to be clarified. Here we report that chronically elevated NPY levels leaded to a modulation of the level of Y2 receptor expression marked with a transient down and upregulation according to the stage of osteoblast differentiation. We also show that NPY is a negative regulator of Y1 receptor expression. The pharmacological activation of Y2 receptor with its agonist resulted in similar effect. Functional analysis also revealed the osteogenic potential of NPY with osteoblast phenotype markers being significantly enhanced in osteoprogenitor cells stimulated by NPY, probably due to the down-regulation of Y1 receptor. In contrasts, these cells exhibit a reduction in calcium deposition in extracellular matrix most likely mediated via Y2 receptor signalling. Furthermore, we show that NPY modulates receptor activator of nuclear factor kB (NF-kB) (RANK) ligand and osteoprotegerin, two key factors regulating bone remodelling. Specifically, NPY inhibits the transcriptional activity of RANKL promoter in osteoprogenitor cells and enhances OPG expression in osteoblasts at early stages of differentiation. However, NPY effect on OPG seemed to be unrelated to Y2 receptor activation. Taken together the present data supported the contribution of NPY pathway in bone homeostasis via a direct action on osteoblasts cells.

Neuropeptide Y inhibits [Ca2+]i changes in rat retinal neurons through NPY Y1, Y4, and Y5 receptors

Neuropeptide Y (NPY) and NPY receptors are widely distributed in the CNS, including the retina, but the role of NPY in the retina is largely unknown. The aim of this study was to investigate whether NPY modulates intracellular calcium concentration ([Ca(2+)](i)) changes in retinal neurons and identify the NPY receptors involved. As NPY decreased the [Ca(2+)](i) amplitudes evoked by 30 mM KCl in only 50% of neurons analyzed, we divided them in two populations: NPY-non-responsive neurons (Delta2/Delta1 > or = 0.80) and NPY-responsive neurons (Delta2/Delta1 < 0.80), being the Delta2/Delta1 the ratio between the amplitude of [Ca(2+)](i) increase evoked by the second (Delta2) and the first (Delta1) stimuli of KCl. The NPY Y(1)/Y(5), Y(4), and Y(5) receptor agonists (100 nM), but not the Y(2) receptor agonist (300 nM), inhibited the [Ca(2+)](i) increase induced by KCl. In addition, the inhibitory effect of NPY on evoked-[Ca(2+)](i) changes was reduced in the presence of the Y(1) or the Y(5) receptor antagonists. In conclusion, NPY inhibits KCl-evoked [Ca(2+)](i) increase in retinal neurons through the activation of NPY Y(1), Y(4), and Y(5) receptors. This effect may be viewed as a potential neuroprotective mechanism of NPY against retinal neurodegeneration.

Presence of the neuropeptide Y1 receptor in tenocytes and blood vessel walls in the human Achilles tendon

Background:Questions remain concerning the mechanisms of the development of chronic pain and impaired function of tendons (tendinosis). Aspects known to occur are cell proliferation, angiogenesis and altered blood flow regulation....

Neuropeptide Y and gamma-melanocyte stimulating hormone (γ-MSH) share a common pressor mechanism of action

Central circuits known to regulate food intake and energy expenditure also affect central cardiovascular regulation. For example, both the melanocortin and neuropeptide Y (NPY) peptide families, known to regulate food intake, also produce central hypertensive effects. Members of both families share a similar C-terminal amino acid residue sequence, RF(Y) amide, a sequence distinct from that required for melanocortin receptor binding. A recently delineated family of RFamide receptors recognizes both of these C-terminal motifs. We now present evidence that an antagonist with Y1 and RFamide receptor activity, BIBO3304, will attenuate the central cardiovascular effects of both gamma-melanocyte stimulating hormone (gamma-MSH) and NPY. The use of synthetic melanocortin and NPY peptide analogs excluded an interaction with melanocortin or Y family receptors. We suggest that the anatomical convergence of NPY and melanocortin neurons on cardiovascular control centers may have pathophysiological implications through a common or similar RFamide receptor(s), much as they converge on other nuclei to coordinately control energy homeostasis.

Platelet neuropeptide Y (NPY) and the collateral and capillary networks in skeletal muscle ischemia

Previously, we showed that sympathetically‐derived or exogenous NPY promotes ischemic revascularization after femoral artery ligation (FAL) in rodents by activating Y2 receptors and dipeptidyl peptidase IV (DPPIV), which forms a Y2/Y5‐preferring agonist. FAL also induced early up‐regulation of Y2 and DPPIV mRNA in adductor (collateral zone, CZ) and gastrocnemius (capillary angiogenesis zone, AZ) muscles and elevated plasma NPY levels, followed by increased platelet NPY levels at 7 and 14 days post‐ligation. The latter findings suggested platelet NPY may play a role in angiogenesis/collateralization after FAL, which is evaluated in this study. In 129/SvlmJ/NPY+/+ mice, FAL induced an increase in capillary density (CD31+ vessels) in the AZ by 14 days (vs. sham), which in NPY‐/‐ remained unchanged (no difference in basal capillary density between NPY+/+ and NPY‐/‐ mice.). Transfer of NPY‐/‐ platelets into platelet‐depleted (Busulfan 25 mg/kg, i.p.) NPY+/+ mice attenuated the angiogenic response in the AZ, while NPY+/+ platelet transfer into NPY‐/‐ mice significantly increased the density of CD31+ vessels in this region. In a separate group of mice, adductor and plantar perfusion were decreased in NPY‐/‐ mice after FAL. These data suggest that NPY's effect on both the collateral and capillary networks promote ischemic revascularization and is, at least in part, mediated by platelet NPY.

Zhou et al. reply

Replying to: C. H. Cotton, J. Flint & T. G. Campbell , 10.1038/nature07927 (2009) The inability of Cotton 1 to detect an effect of a functional haplotype (and locus) of neuropeptide Y (NPY), a stress regulatory neuropeptide, on neuroticism is interesting. Although it is important to measure effects of functional loci on complex behaviours, the strength of our study2, and primary basis of its conclusions, was the larger and convergent effects of NPY on intermediate phenotypes, including regional brain responses to emotional stimuli and pain, and brain NPY messenger RNA and plasma NPY levels. Eysenck Neuroticism is a trait that we did not directly investigate. We reported modest association of NPY with two Harm Avoidance subscales from the Tridimensional Personality Questionnaire. Association of NPY with the complex trait of anxiety, especially when measured differently, is not the first place we would look to validate our results.

PreproNPY Pro7 protects against depression despite exposure to environmental risk factors

Background There is extensive evidence, from both clinical cases and rodent models, for reduced levels of the widely expressed neuropeptide Y (NPY) in anxiety and depressive disorders. The rare allele of the Leu7Pro polymorphism in the signal peptide of preproNPY has been associated with higher processing into mature NPY, and higher NPY levels in plasma and cerebrospinal fluid. The Pro7 allele was proposed to protect against depression in a small Swedish clinical sample (Heilig M., Zachrisson O., Thorsell A., Ehnvall A., Mottagui-Tabar S., Sjögren M., Asberg M., Ekman R., Wahlestedt C., Agren H., 2004. Decreased cerebrospinal fluid neuropeptide Y (NPY) in patients with treatment refractory unipolar major depression: preliminary evidence for association with preproNPY gene polymorphism. J. Psychiatr. Res. 38, 113–121). Method Leu7Pro was analyzed in a large well-characterized longitudinal population-based sample of adult Swedes with data on life situation and life history, including 461 with depression diagnosis, 157 with anxiety diagnosis and 1514 healthy individuals with no symptom of psychopathology. Results Pro7 was rarer in depression cases than in healthy individuals (OR = 2.7; P = 0.0004). The protective effect of Pro7 was similar despite exposure to known environmental vulnerability factors. Pro7 appeared with similar effect size in those with an anxiety diagnosis, but this was not statistically significant (OR = 2.3; P = 0.06). Limitation The size of the anxiety sample and possibly some recall bias of childhood conditions. Conclusion Pro7 allele of preproNPY protected against depression among Swedes. Pro7 is not common, but was found to exert its protective effect also in an environment-induced vulnerable state. This supports a protective effect of NPY in line with previous reports suggesting anxiolytic-like and antidepressant-like effects of NPY.

Neuronal signaling and the regulation of bone remodeling. new insights into the role of neuropeptide Y Y1 and Y2 receptors in osteoblast function

Event Abstract Back to Event Neuronal signaling and the regulation of bone remodeling. new insights into the role of neuropeptide Y Y1 and Y2 receptors in osteoblast function Liliana Teixeira1*, Daniela Sousa1, Ana F. Nunes2, Monica Mendes-Sousa2, Herbert Herzog3 and Meriem Lamghari1 1 Universidade do Porto, INEB – Instituto de Engenharia Biomedica, Divisao de Biomateriais, NewTherapies group, Portugal 2 Universidade do Porto, Nerve regeneration group, IBMC - Instituto de Biologia Molecular e Celular, Portugal 3 Garvan Institute of Medical Research, Neuroscience Program, Australia Neuropeptide Y (NPY) has recently emerged as a potential regulator of bone homeostasis. However, the relevance of NPY’s role in osteoblast activity and the biological functions involving NPY receptors in bone homeostasis remain to be clarified. Here we report that chronically elevated NPY levels leaded to a modulation of the level of Y2 receptor expression marked with a transient down and upregulation according to the stage of osteoblast differentiation. We also show that NPY is a negative regulator of Y1 receptor expression. The pharmalogical activation of Y2 receptor with its agonist resulted in similar effect. Functional analysis also revealed the osteogenic potential of NPY with osteoblast phenotype markers being significantly enhanced in osteoprogenitor cells stimulated by NPY, probably due to the down-regulation of Y1 receptor. In contrasts, these cells exhibit a reduction in calcium deposition in extracellular matrix most likely mediated via Y2 receptor signalling. Furthermore, we show that NPY modulates receptor activator of nuclear factor kB (NF– kB) (RANK) ligand and osteoprotegerin, two key factors regulating bone remodelling. Specifically, NPY inhibits the transcriptional activity of RANKL promoter in osteoprogenitor cells and enhances OPG expression in osteoblasts at early stages of differentiation. However, NPY effect on OPG seemed to be unrelated to Y2 receptor activation. Conference: 11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009. Presentation Type: Poster Presentation Topic: Neuronal Communication Citation: Teixeira L, Sousa D, Nunes AF, Mendes-Sousa M, Herzog H and Lamghari M (2009). Neuronal signaling and the regulation of bone remodeling. new insights into the role of neuropeptide Y Y1 and Y2 receptors in osteoblast function. Front. Neurosci. Conference Abstract: 11th Meeting of the Portuguese Society for Neuroscience. doi: 10.3389/conf.neuro.01.2009.11.151 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 12 Aug 2009; Published Online: 12 Aug 2009. * Correspondence: Liliana Teixeira, Universidade do Porto, INEB – Instituto de Engenharia Biomedica, Divisao de Biomateriais, NewTherapies group, Porto, Portugal, L.S.MoreiraTeixeira@tnw.utwente.nl Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Liliana Teixeira Daniela Sousa Ana F Nunes Monica Mendes-Sousa Herbert Herzog Meriem Lamghari Google Liliana Teixeira Daniela Sousa Ana F Nunes Monica Mendes-Sousa Herbert Herzog Meriem Lamghari Google Scholar Liliana Teixeira Daniela Sousa Ana F Nunes Monica Mendes-Sousa Herbert Herzog Meriem Lamghari PubMed Liliana Teixeira Daniela Sousa Ana F Nunes Monica Mendes-Sousa Herbert Herzog Meriem Lamghari Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Anorexigenic effect of cholecystokinin is lost but that of CART (Cocaine and Amphetamine Regulated Transcript) peptide is preserved in monosodium glutamate obese mice

Monosodium glutamate (MSG) treatment of neonatal mice results in a selective damage to the arcuate nucleus (ARC) and development of obesity with increased adiposity at sustained body weight in the adulthood. Feeding pattern of the MSG obese mice is unusual. Our previous results showed that after 24-h fasting, MSG mice consumed negligible amount of food in several hours and therefore, it was impossible to register the effect of peptides attenuating food intake such as cholecystokinin (CCK) or cocaine- and amphetamine-regulated transcript (CART) peptide. To overcome this problem, two findings were used: firstly, orexigenic effect of neuropeptide Y (NPY) was attenuated both by CCK or CART peptide in lean fed mice and secondly, orexigenic effect of NPY was preserved in fed rats with MSG obesity. In this study, short-term food intake in fed lean and MSG obese C57BL/6 male mice was measured after simultaneous central administration of orexigenic NPY with either CART peptide or peripherally administered CCK. Anorexigenic action of exogenous CART peptide was preserved in MSG obese mice. On the other hand, satiety effect of exogenous CCK was completely lost in MSG obese mice. In conclusion, effective leptin signaling in ARC is necessary for satiety effect of CCK.

Neuropeptide Y augments cocaine self-administration and cocaine-induced hyperlocomotion in rats

Food restriction and deprivation are known to modulate drug-related behaviors. However, the mechanisms through which metabolic manipulations intercede the rewarding effects of drug reward are unknown. Neuropeptide Y (NPY) is thought to be critically involved in the regulation of energy balance. Central administration of NPY induces feeding in sated animals, and importantly, is reported to increase the rewarding properties of food. NPY has also been shown to be involved in drug-related behavior. We have recently demonstrated that NPY injections augmented on-going heroin self-administration and induced a reinstatement of heroin seeking. The present study sought to support and expand our previous finding on NPY's role in addictive drugs-related behaviors by examining the effects of NPY on cocaine-induced locomotor hyperactivity and cocaine self-administration. In Experiment 1, rats received NPY injections (0.0, 2.5, 5.0 μg/rat, ICV), followed by cocaine administration (0.0, 1.0, 5.0, and 10.0 mg/kg, IP) and their locomotor activity was monitored over 90 min. In Experiment 2, rats were trained to self-administer cocaine (0.50 mg/kg/infusion) during one 3-h session per day for 12 days. Once trained, NPY (0.0, 4.0, 10.0 μg/rat, ICV) was administered 15 min prior to the self-administration session. Results revealed that NPY injections augmented cocaine-induced hyperactivity and moderately increased cocaine self-administration. Together with our previous findings, these results suggest that NPY is involved, albeit to a limited extent, in the augmenting effect of food deprivation on drug-related behaviors.

Possible role of the histaminergic system in autonomic and cardiovascular responses to neuropeptide Y

Previous studies have demonstrated that neuropeptide Y (NPY) affects blood pressure (BP) in anesthetized rats. Here, we examined the effects of the third cerebral ventricular (3CV) injection of various doses of NPY on renal sympathetic nerve activity (RSNA) and BP in anesthetized rats. 3CV injection of NPY suppressed RSNA and BP in a dose-dependent manner. Moreover, suppressing effects of NPY on RSNA and BP were eliminated by lateral cerebral ventricular (LCV) preinjection of thioperamide, an antagonist of histaminergic H3-receptor, not diphenhydramine, an antagonist of histaminergic H1-receptor. In addition, 3CV injection of NPY accelerated gastric vagal nerve activity (GVNA) and inhibited brown adipose tissue sympathetic nerve activity (BAT-SNA) of anesthetized rats, and lowered brown adipose tissue temperature (BAT-T) of conscious rats. Thus, these evidences suggest that central NPY affects autonomic nerves containing RSNA, GVNA or BAT-SNA, and BP by mediating central histaminergic H3-receptors.

Neuropeptide Y suppresses ethanol drinking in ethanol-abstinent, but not non–ethanol-abstinent, Wistar rats

In outbred rats, increases in brain neuropeptide Y (NPY) activity suppress ethanol consumption in a variety of access conditions, but only following a history of ethanol dependence. NPY reliably suppresses ethanol drinking in alcohol-preferring rats, and this effect is augmented following a period of ethanol abstinence. The purpose of this experiment was to examine the effects of NPY on two-bottle choice ethanol drinking and feeding in Wistar rats that had undergone chronic ethanol vapor exposure, cycles of ethanol abstinence, or both. Ethanol-drinking Wistar rats were given 6 weeks of access to 15% (vol/vol) ethanol and water followed by either: two cycles of 1 week ethanol vapor exposure and 2 weeks with no ethanol; two cycles of 1 week ethanol bottle availability and 2 weeks with no ethanol; or 2 weeks of ethanol vapor exposure. Rats were infused intracerebroventricularly with one of four NPY doses (0.0, 2.5, 5.0, or 10.0 μg) following the ethanol exposure patterns described above, and tested for ethanol drinking and feeding in a two-bottle choice situation. NPY dose dependently increased food intake regardless of ethanol exposure history, but suppressed ethanol drinking only in rats that underwent cycles of ethanol access and ethanol abstinence. These results support the notion that dysregulation of brain NPY systems during chronic intermittent ethanol exposure is important in the motivational drive for subsequent relapse to ethanol drinking.