Neuropeptides RSS feed: Articles in Press. The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the idenfication of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems. The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials. Original papers predominate. Manuscripts may be of any length, but must be complete studies; preliminary communications are not accepted. Review articles and hypothesis papers are welcomed, and will be evaluated in the same way as experimental papers. Authors intending to submit a review are advised to communicate their intentions to the Editor, to avoid possible duplication. To order this journal online, visit http://intl.elsevierhealth.com/journals/npep http://www.neuropeptidesjournal.com//inpress?rss=yesElsevier Inc.en © 2010 Elsevier Ltd. All rights reserved. Neuropeptides0143-41792010-03-02 © 2010 Elsevier Ltd. All rights reserved. healthpermissions@elsevier.comhttp://www.neuropeptidesjournal.com/article/PIIS0143417910000089/abstract?rss=yesAbstract: The effects of various protease inhibitors on naloxone-precipitated withdrawal jumping were examined in morphine-dependent mice. The doses of morphine were subcutaneously given twice daily for 2days (day 1, 30mg/kg; day 2, 60mg/kg). On day 3, naloxone (8mg/kg) was intraperitoneally administered 3h after final injection of morphine (60mg/kg), and the number of jumping was immediately recorded for 20min. Naloxone-precipitated withdrawal jumping was significantly suppressed by the intracerebroventricular administration of N-ethylmaleimide (0.5nmol) and Boc-Tyr-Gly-NHO-Bz (0.4nmol), inhibitors of cysteine proteases involved in dynorphin degradation, 5min before each morphine treatment during the induction phase, with none given on the test day, as well as by dynorphin A (62.5pmol) and dynorphin B (250pmol). However, amastatin, an aminopeptidase inhibitor, phosphoramidon, an endopeptidase 24.11 inhibitor, and captopril, an angiotensin-converting enzyme inhibitor, caused no changes. The present results suggest that cysteine protease inhibitors suppress naloxone-precipitated withdrawal jumping in morphine-dependent mice, presumably through the inhibition of dynorphin degradation.Suppressive effects by cysteine protease inhibitors on naloxone-precipitated withdrawal jumping in morphine-dependent mice - Corrected ProofKoichi Tan-No, Tasuku Sato, Masakazu Shimoda, Osamu Nakagawasai, Fukie Niijima, Shunsuke Kawamura, Seiichi Furuta, Takumi Sato, Susumu Satoh, Jerzy Silberring, Lars Terenius, Takeshi Tadano10.1016/j.npep.2010.02.001Neuropeptides (2010)2010-03-02Neuropeptides2010-03-02http://www.neuropeptidesjournal.com/article/PIIS0143417910000077/abstract?rss=yesAbstract: It is known that intrathecal administration of substance P (SP) induces thermal hyperalgesia, whereas hemokinin-1 (HK-1), a member of the same tachykinin family as SP, hardly induces thermal hyperalgesia; however, the underlying mechanism remains to be elucidated. Therefore, we aimed to clarify which amino acid of these peptides contributes to the induction of thermal hyperalgesia. When two chimera peptides between the N-terminal region of SP and the C-terminal region of HK-1, and vice versa, SP (1–5)/HK-1 and HK-1 (1–5)/SP, were intrathecally administered, SP (1–5)/HK-1 induced thermal hyperalgesia whereas HK-1 (1–5)/SP had hardly any effect; furthermore, thermal hyperalgesia was induced by only C-terminal fragments of HK-1 and SP. These findings indicate that the N-terminal region of HK-1 is involved in the non-induction of thermal hyperalgesia. Next, we synthesized and intrathecally administered these chimera peptides in which part of the N-terminal region of HK-1 was replaced with that of SP, and vice versa, and all synthesized peptides induced thermal hyperalgesia. Both SP (1–2)/HK-1 and HK-1 (1–4)/SP certainly induced thermal hyperalgesia, although HK-1 and HK-1 (1–5)/SP had hardly any effect; therefore, it is probable that Ser at the 2nd position and Arg at the 5th position of HK-1 may be involved in the non-induction of thermal hyperalgesia. Furthermore, peptides in which amino acid at the 3rd and/or 4th positions of HK-1 was replaced with that of SP were synthesized. Intrathecal administration of HK-1 (1–2,4–5)/SP, but not HK-1 (1–2,5)/SP and HK-1 (1–3,5)/SP, hardly induced thermal hyperalgesia. These findings indicate that three amino acids, Ser, Thr and Arg at the 2nd, 4th and 5th positions of HK-1, respectively, regulate the induction of thermal hyperalgesia by HK-1.The amino-terminal region of hemokinin-1 regulates the induction of thermal hyperalgesia in rats - Corrected ProofN. Sunakawa, R. Naono, T. Ikeda, O. Matsushima, S. Sakoda, T. Nishimori10.1016/j.npep.2010.01.003Neuropeptides (2010)2010-02-22Neuropeptides2010-02-22http://www.neuropeptidesjournal.com/article/PIIS0143417910000065/abstract?rss=yesAbstract: The effect of tachykinin neurokinin NK2 receptors activation on intestinal propulsion and colorectal sensitivity was studied in 7–15days old newborn rats.In a first set of experiments investigating the intestinal transit, the selective NK2 receptor agonist, [βAla8]NKA-(4-10) was used. It produced an increase of the small intestinal transit measured by charcoal test of 54%, that was inhibited in a dose-dependent manner by nepadutant ([N4-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-l-asparaginyl-l-aspartyl-l-tryptophyl-l-phenylalanyl-l-2,3-diaminopropionyl-l-leucyl]-C-4.2-N-3.5-lactam-C-1.6-N-2.1-lactam), a known selective NK2 receptor antagonist, orally administered 2–48h before the challenge with the NK2 receptor agonist. Nepadutant did not affect the basal intestinal propulsion and showed a good oral bioavailability and long duration of action.In another set of experiments investigating visceral sensitivity, a fixed distension volume of a balloon inserted intrarectally in 14–15days old newborns rats produced abdominal contractions (AC) that were increased after colonic application of acetic acid (50μl, 0.5%). In this latter condition nepadutant, at 0.5 and 2.5mg/kg p.o., significantly reduced the resulting AC. In control rats, untreated with acetic acid, nepadutant did not affect AC evoked by colorectal distension.These findings show for the first time two models to assess intestinal motility and visceral sensitivity in newborn rats and indicate nepadutant as a valuable tool to assess the role of NK2 receptors in the intestinal propulsive and nociceptive activity in infants.Influence of tachykinin NK2 receptors on intestinal sensitivity and motility in newborn rats - Corrected ProofM. Tramontana, S. Evangelista, S. Giuliani, S. Manzini, S. Robelet, V. Girod, C.A. Maggi10.1016/j.npep.2010.01.002Neuropeptides (2010)2010-02-08Neuropeptides2010-02-08http://www.neuropeptidesjournal.com/article/PIIS0143417909001528/abstract?rss=yesAbstract: Cocaine- and amphetamine-regulated transcript (CART) peptides modulate anxiety, food intake, endocrine function, and mesolimbic dopamine related reward and reinforcement. Each of these disparate behaviors takes place during the state of wakefulness. Here, we identify a potential wake promoting role of CART by characterizing its effects upon sleep/wake architecture in rats. Dose-dependent increases in wake were documented following intracerebroventricular CART 55–102 administered at the beginning of the rat’s major sleep period. Sustained wake was observed for up to 4h following delivery of 2.0μg of CART peptide. The wake promoting effect was specific to active CART 55–102 because no effect on sleep/wake was observed with the inactive form of the peptide. Increased wake was followed by robust rebound in NREM and REM sleep that extended well into the subsequent lights-off, or typical wake period, of the rat. These findings point to a potential novel role for CART in regulating wakefulness.Wake promoting effects of cocaine and amphetamine-regulated transcript (CART) - Corrected ProofGlenda L. Keating, Michael J. Kuhar, Donald L. Bliwise, David B. Rye10.1016/j.npep.2009.12.013Neuropeptides (2010)2010-02-01Neuropeptides2010-02-01http://www.neuropeptidesjournal.com/article/PIIS0143417909001541/abstract?rss=yesAbstract: The central mechanism that mediates litorin-induced satiety is poorly understood, and has not been studied in a non-mammalian species. Therefore, the aim of this study was to determine if litorin-induced satiety in an alternative vertebrate model, the chick, and to elucidate some of the central mechanisms that are associated with this response. In Experiment 1, chicks responded to intracerebroventricular (ICV) injection of litorin with reduced food intake at all doses tested (0.1, 1.0, and 10nmol), while concurrently, an anti-dipsogenic effect was observed in the two higher doses tested. Whole blood glucose concentrations were not affected. In Experiment 2, chicks that were food-withheld did not reduce their water intake after ICV litorin injection. To determine if litorin affected behaviors unrelated to ingestion, a comprehensive behavior analysis was conducted as Experiment 3. Of the behaviors observed, only the number of feeding pecks was reduced. Other behaviors such as movement, defecation, escape, posture, or deep rest were not affected. Lastly, in Experiment 4, litorin-treated chicks had an increased number of c-Fos immunoreactive cells in the magnocellular division of the paraventricular nucleus. The arcuate nucleus, dorsomedial nucleus, lateral hypothalamus, parvicellular division of the paraventricular nucleus, suprachiasmatic nucleus, periventricular nucleus and the ventromedial hypothalamus were not affected. Therefore, we conclude that ICV litorin causes anorexigenic effects in chicks associated with changes in hypothalamic chemistry that appear to be behavior specific.Central litorin injection is associated with primary anorexigenic effects that coincide with activation of the magnocellular division of the paraventricular nucleus - Corrected ProofMark A. Cline, Stuart A. Cofield, Tetsuya Tachibana10.1016/j.npep.2009.12.015Neuropeptides (2010)2010-02-01Neuropeptides2010-02-01http://www.neuropeptidesjournal.com/article/PIIS0143417910000053/abstract?rss=yesAbstract: Gut-derived peptides are known to regulate food intake by activating specific receptors in the brain, but the target nuclei and neurons influenced are largely unknown. Here we show that peripherally administered pancreatic polypeptide (PP) stimulates neurons in key nuclei of the hypothalamus critical for appetite and satiety regulation. In the lateral hypothalamic area (LHA), also known as the feeding center, neurons expressing the orexigenic neuropeptide orexin co-localize with the early neuronal activation marker c-Fos upon i.p. injection of PP into mice. In the ventromedial hypothalamus (VMH), also known as the satiety center, neurons activated by PP, as indicated by induction of c-Fos immunoreactivity, express the anorexigenic brain-derived neurotrophic factor (BDNF). Activation of neurons in the LHA and VMH in response to PP occurs via a Y4 receptor-dependent process as it is not seen in Y4 receptor knockout mice. We further demonstrate that in response to i.p. PP, orexin mRNA expression in the LHA is down-regulated, with Y4 receptors being critical for this effect as it is not seen in Y4 receptor knockout mice, whereas BDNF mRNA expression is up-regulated in the VMH in response to i.p. PP in the fasted, but not in the non-fasted state. Taken together these data suggest that PP can regulate food intake by suppressing orexigenic pathways by down-regulation of orexin and simultaneously increasing anorexigenic pathways by up-regulating BDNF.Y4 receptors and pancreatic polypeptide regulate food intake via hypothalamic orexin and brain-derived neurotropic factor dependent pathways - Corrected ProofAmanda Sainsbury, Yan-Chuan Shi, Lei Zhang, Aygul Aljanova, Zhou Lin, Amy D. Nguyen, Herbert Herzog, Shu Lin10.1016/j.npep.2010.01.001Neuropeptides (2010)2010-02-01Neuropeptides2010-02-01http://www.neuropeptidesjournal.com/article/PIIS0143417909001474/abstract?rss=yesAbstract: Recent research has highlighted a potential role for neuropeptide Y (NPY) and its Y1 receptor in the development of schizophrenia. Genetic as well as molecular biological studies have demonstrated reduced levels of NPY in schizophrenia patients. Importantly, Y1 receptors may mediate some of the potential effects of NPY on schizophrenia, as decreased Y1 receptor expression has been found in the lymphocytes of schizophrenia patients. To clarify NPY’s role in schizophrenia, we investigated a genetic animal model for Y1 deficiency in regard to (i) acoustic startle response (ASR), (ii) habituation to ASR and (iii) sensorimotor gating [i.e. prepulse inhibition (PPI)] using two different PPI protocols. Mutant and wild type-like mice were screened for baseline behaviours and after pharmacological challenge with the psychotropic drugs dexamphetamine (DEX) and MK-801. Y1 knockout mice (Y1−/−) showed a moderate reduction of the ASR and an impaired ASR habituation at baseline and after DEX treatment. The baseline PPI performance of Y1 mutant mice was unaltered their response to DEX and MK-801 challenge was moderately different compared to control mice, which was dependent on the PPI protocol used. MK-801 challenge had a protocol-dependent differential effect in Y1−/− mice and DEX a more pronounced impact at the highest prepulse intensities. In conclusion, it appears that the Y1 receptor influences the acoustic startle response and its habituation but does not play a major role in sensorimotor gating. Further explorations into the effects of Y1 deficiency seem valid.Acoustic startle response and sensorimotor gating in a genetic mouse model for the Y1 receptor - Corrected ProofT. Karl, R. Chesworth, L. Duffy, H. Herzog10.1016/j.npep.2009.12.008Neuropeptides (2010)2010-01-25Neuropeptides2010-01-25http://www.neuropeptidesjournal.com/article/PIIS014341790900153X/abstract?rss=yesAbstract: Anxiety and depression are highly prevalent disorders of mood posing significant challenges to individuals and society. Current evidence indicates no single neurobiological determinant underpins these conditions and an integrated approach in both research and treatment is expedient. Basic, behavioral, and clinical science indicates various stress-responsive neuropeptides in the neuroendocrine, autonomic, and behavioral pathophysiology of stress-related disorders including anxiety and depression. This review draws on recent research to capture the consensus and implications of neuropeptide research concerning the pathogenesis of anxiety and depression.Pathogenic involvement of neuropeptides in anxiety and depression - Corrected ProofBrett Alldredge10.1016/j.npep.2009.12.014Neuropeptides (2010)2010-01-25Neuropeptides2010-01-25NEWS AND REVIEWShttp://www.neuropeptidesjournal.com/article/PIIS0143417909001693/abstract?rss=yesAbstract: The function of angiotensin peptides is dependent upon the action of several aminopeptidases (APs) termed angiotensinases. Soluble (SOL) and membrane (MEM)-bound alanyl-AP (AlaAP) and cystinyl-AP (CysAP) are involved in the metabolism of angiotensins and related to the modulation of behavior and memory. To study the interactions between angiotensinase activity in the hippocampus and behavioral lateralization, Wistar rats were selected on the basis of their performance in the paw preference test (left-handed, ambidextrous and right-handed) and the activities of SOL-AlaAP/CysAP and MEM-AlaAP/CysAP were measured in the both hippocampuses. We observed that: (1) the left hippocampus had higher activities of SOL-AlaAP/CysAP and MEM-AlaAP/CysAP than the right hippocampus; (2) rats showed significant differences in the activities of SOL-AlaAP/CysAP and MEM-AlaAP/CysAP in the hippocampus depending on the behavioral lateralization detecting by paw preference; (3) in three groups of rats, hemispheric dominance – %R/T [%R/T=right hemisphere/(right hemisphere+left hemisphere)×100] activities of MEM-AlaAP, SOL-CysAP and MEM-CysAP was significantly different whereby %RT was lower in left-handed, higher in ambidextrous and intermediate in right-handed rats; (4) individual %R/T activities of SOL-CysAP and MEM-CysAP in the hippocampus were positively correlated with paw preference scores. Finally, we used the passive avoidance behavior test to demonstrate the differences of long-term memory among the three groups. These results suggested that the asymmetric activity of angiotensinase in the rat hippocampus may be associated with both the direction and the intensity of behavioral lateralization as expressed by paw preference.Correlations between angiotensinase activity asymmetries in the brain and paw preference in rats - Corrected ProofHe-ming Wu, Chao Wang, Xue-lian Wang, Ling Wang, Chong-wang Chang, Peng Wang, Guo-dong Gao10.1016/j.npep.2009.12.016Neuropeptides (2010)2010-01-25Neuropeptides2010-01-25http://www.neuropeptidesjournal.com/article/PIIS0143417909001413/abstract?rss=yesAbstract: Opioid signaling has been strongly implicated in driving palatable food consumption. The nucleus accumbens (NAcc) is one important site of this effect; hyperphagia elicited by administration of exogenous mu opioid receptor (MOR) ligands in this brain region has been well documented. However, the role that endogenous opioid ligands in the NAcc play in controlling food intake remains poorly understood. Enkephalins, which signal through both the MOR and delta opioid receptor (DOR), are highly expressed within a subset of NAcc neurons, and have been shown to be sensitive to manipulations of diet and motivation. To investigate a potential role for these signaling molecules in regulating palatability-driven consumption, we measured high fat chow intake in rats following a series of pharmacological manipulations of NAcc opioid signaling. NAcc infusion of the MOR agonist [d-Ala2, N-MePHe4, Gly-ol]-enkephalin (DAMGO) robustly increased palatable food intake, as has previously been demonstrated. In contrast, neither infusion of Met-enkephalin, its synthetic analogue [d-Ala2] Met-enkephalin (DALA) nor the DOR-specific ligand [d-Pen2, Pen5]-enkephalin (DPDPE) had significant effects on food intake. However, when administered in combination with DAMGO, DPDPE significantly suppressed the magnitude of DAMGO-evoked feeding. Further analysis of DPDPE effects revealed that the drug strongly increased locomotor activity. Suppressive effects on feeding, then, may have occurred through competition between feeding and locomotion for behavioral expression.Modulation of feeding and locomotion through mu and delta opioid receptor signaling in the nucleus accumbens - Corrected ProofYoshihiro Katsuura, Sharif A. Taha10.1016/j.npep.2009.12.002Neuropeptides (2009)2009-12-31Neuropeptides2009-12-31