Endorphins Research Papers - Academia.edu (original) (raw)

The opiate antagonist naloxone was effective in reducing self-abusive behavior in two mentally retarded clients with an extensive history of such behavior. Three doses of naloxone (0.1, 0.2, 0.4 rag) were compared with a vehicle solution in a double-blind, crossover design. Naloxone greatly attenuated self-abusive episodes in one client and eliminated them entirely in the second client. In addition, use of self-restraining behavior by one client was reduced. The findings suggested that some clients with self-injurious behavior may have disturbances of the endogenous opiate system. Maintenance of self-abuse by tonically elevated pain threshold and~or by the putative addictive characteristics of such behavior was discussed.

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- Pain, Intellectual Disability, Applied, Developmental disabilities
- by Ludovica Marcellini
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- Organic Chemistry, Medicinal Chemistry, Cell Division, Circular Dichroism

The pathogenic role of self-addiction. Addiction to an endogenous chemical is a new paradigm termed 'self-addiction'. It may contribute to the development of certain habits, the pathological nature of which may set-in on the basis of this "self-addictive"dimension. Pathological eating habits could be inscribed in this perspective. Two extreme situations. In well-fed populations, the ingestion of food does not represent a limiting phase in the global feeding process. Its pathological management may, however, lead to two extreme situations: the absence of ingestion (anorexia) and excessive ingestion (bulimia). In favour of the self-addictive hypothesis. Eating disorders are associated with abnormal levels of endorphins and share clinical similarities with psychoactive drug abuse. The key role of endorphins has recently been demonstrated in animals with regard to certain aspects of normal, pathological and experimental eating habits (food restriction combined with str...

- by Yasmine Lienard
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- Eating Disorders, Dopamine, Endorphins, Personality Inventory
- by George B Stefano
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- Cognitive Science, Invertebrates, Neurons, Time Factors

Skin stress response system (SSRS) involves corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC)-derived peptides, such as adrenocorticotropic hormone (ACTH), a-melanocyte-stimulating hormone (MSH) and bendorphin that are locally generated in response to locally provided stressors or proinflammatory cytokines. This system would restrict tissue damage and restore local homoeostasis. Trichloroacetic acid (TCA) is one of the most widely used peeling agents and applied for cosmetic treatment of photodamaged skin. However, the biological mechanism responsible for TCA peeling has yet to be fully determined. While our investigation focused on the inflammation and wound healing pathways, in the recent study, we have examined involvement of the SSRS as the third pathway. Mostly depending on our findings that TCA peeling activates the SSRS by inducing the POMC expression of keratinocytes in the CRH-independent manner, together with the results reported by other researchers, we can say that the biological effect of POMC seems to be responsible for the TCAinduced epidermal SSRS activation.

- by Nobuo Kanazawa and +1
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- Corticotropin Releasing Hormone, Keratinocytes, Peptides, Skin

Anttaver~tve propernes ofoplolds in the condmoned taste averston test tn the rat PHARMACOL BIOCHEM BEHAV 27(3) 437-441, 1987-The antlaverslve effect of/z-, K-and 8-opmld receptor agomsts against condltmned taste aversmn (CTA) induced by apomorphme, hthmm chloride and copper sulphate in the rat was studied, in order to evaluate whether preventmn of CTA Is a suitable model for the study of ant~emet~cs Anti-aversion was not a general characteristic of all opined substances tested Only one dose of the/z-agomst morphine and only one dose of the K-agonlst ethylketocyclazocme had a consistent antlaverslve effect against CTA mduced by apomorphme, one dose of the 8-agomst [D-AIa 2, Met~]enkephahnamide antagomzed the aversmn mduced by hthlum chloride As the results do not correspond to our prewous findings on the antlemeUc effects of these oplolds m the dog (all/z-and K-agomsts tested hawng an anUemetlc effect), we conclude that the CTA test cannot be used as a screening test for potentially ant~emetlc drugs

- by Romain Lefebvre
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- Classical Conditioning, Taste, Morphine, Methadone

Several lines of evidence suggest that the endogenous opioid peptides endorphins may play a role in the defensive response of the organism to stress. The present paper summarizes these findings as well as evidence linking endorphins to the anterior pituitary polypeptide hormone adrenocorticotropin (ACTH). Evidence is presented that endorphins may function as trophic hormones in peripheral target organs such as the adrenal medulla and the pancreas. As such they may be part of the physiological mechanisms that mediate adrenaline and glucagon release in response to stress. Endorphins (enkephalins) are also suggested to play a role in the control of the pituitary gland during stress. In such capacity they may act as hormone-releasing or inhibiting factors. Finally, endorphins appear to play a role in the behavioral concomitants of stress. In such capacity endorphins are suggested to function as modulators of neural systems that mediate the elaboration and expression of the reactive/affe...

- by Shimon Amir
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- Chemistry, Pain, Emotions, Affect
- by Gunvor Gard
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- Depression, Treatment Outcome, Exercise therapy, Exercise

Following research evidence that suggests that the gratification derived from the consumption of sad content can be better explained by the experience of meaningful affect/feelings of being moved than by the experience of sadness, this research reconciled solutions to the paradox of pleasurable sadness from the media psychology literature with models of altruism from positive psychology, ethology, and behavioral economics. It is proposed that compassion incentivizes narrative engagement and that the gratification derived from the consumption of sad content follows an overall positive valuation of the somatic changes felt while engaged with a story. This research tested an association between experiencing feelings of compassion as a consequence of consuming sad content and engagement, between engagement and being moved, and between gratification and changes in the levels of salivary Interleukin 18 (IL-18) as a proxy for the activity of the μ-opioid receptors in the brain. Results suggested a strong and positive correlation between compassion, engagement, being moved, and gratification. Results from the physiological measures suggested a negative correlation between IL-18 and gratification that agrees with models of social motivation predicting that hypoactivity of the μ-opioid receptors results in a craving for social contact. Nevertheless, the low number of valid cases and questions about the reliability of the biomarker used demand a cautious interpretation of the association.

- by Carlos A Gonzalez Velazquez
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- Compassion, Enjoyment, Paradox, Sadness

The human body has approximately 1 trillion neurons, each of which has a cell body with a nucleus that contains the genetic material that determines how the cell functions (Feldman, 2008). By thinking of the nervous system as the highway and the neurons as the vehicles on that highway, we can see how “the nervous system is (considered to be) the pathway for the instructions that permit our bodies to carry out such precise activities” (p. 61). In this paper, we discover why neurons are called “the basic elements of behavior” by examining them as the nerve cells that allow our brains to transport and coordinate the messages of our thoughts, actions, and deeds.

Due to recent changes of gambling laws, accessibility to gambling has become more widespread and thus, there has also been an increase in the prevalence of pathological gambling (PG). The wide range of social, economic, and psychological problems associated with PG are well known. There is a need for better understanding of PG and this review attempts to do so. Literature searches using the Medline and PsycINFO databases were used. Critical examining of the literature showed that familial/genetic, sociological, and individual factors (e.g., an individual's personality, biochemistry, psychological states, and cognitions) are implicated in the development and maintenance of PG, yet at present, the evidences are not solid. Similarly, there have been a lot of theories for PG but again, none of them are solid enough to provide a clear understanding of PG. Recent psychological-based theories seem to provide some solid ground for further research. We highlight four areas for future consideration for research. (1) Most studies have generalized findings from one form of gambling to another. It is suggested that it is now not tenable to consider gambling as a single phenomenon that can explain all forms of gambling.

- by Wayne Skinner
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- Genetics, Psychology, Clinical Psychology, Addiction

A B S T R A C T Behavioural synchronization has been shown to facilitate social bonding and cooperation but the mechanisms through which such effects are attained are poorly understood. In the current study, participants interacted with a pre-recorded confederate who exhibited different rates of synchrony, and we investigated three mechanisms for the effects of synchrony on likeability and trusting behaviour: self-other overlap, perceived cooperation, and opioid system activation measured via pain threshold. We show that engaging in highly synchronous behaviour activates all three mechanisms, and that these mechanisms mediate the effects of synchrony on liking and investment in a Trust Game. Specifically, self-other overlap and perceived cooperation mediated the effects of synchrony on interpersonal liking, while behavioural trust was mediated only by change in pain threshold. These results suggest that there are multiple compatible pathways through which synchrony influences social attitudes, but endogenous opioid system activation, such as β-endorphin release, might be important in facilitating economic cooperation.

- by Martin Lang and +2
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- Social Interaction, Synchronization, Cooperation, Coordination
- by Julie Le Merrer
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- Biological Sciences, Reward, Brain, Endorphins
- by Larry Normansell
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- Regulation, Emotions, Brain Mapping, Social behavior

1. This review article provides information on the evolutionary history of neuroendocrine and related regulatory mechanisms. It focuses on the presence, diverse roles, and modes of operation of one class of neuropeptides, the endogenous opioids, in insects. 2. Opioid peptides, closely resembling those of vertebrates, have been identified in the brain and related neuroendocrine structures by means of immunocytochemistry and high-pressure liquid chromatography. 3. The demonstration of naloxone-sensitive, high-affinity binding sites for Met-enkephalin-like neuropeptides in the brain and digestive tract of Leucophaea deserves special attention because it provides new insights into the functional significance of opiate receptors paralleling those known in vertebrates. 4. Possible roles of receptor-mediated opioid systems in the insects discussed are regulation of the cyclicity of the female reproductive system, maintenance of normal midgut function mediated by the recurrent nerve, and locomotor activity.

- by George B Stefano
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- Brain, Cellular and Molecular Neurobiology, Insects, Evolutionary History
- by Manuel Millan
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- Pain, Pain Management, Chronic Disease, Spinal Cord

The placebo effect is very well known, being replicated in many scientific studies. At the same time, its exact mechanisms still remain unknown. Quite a few hypothetical explanations for the placebo effect have been suggested, including faith, belief, hope, classical conditioning, conscious/subconscious expectation, endorphins, and the meaning response.This article argues that all these explanations may boil down to autosuggestion, in the sense of "communication with the subconscious." An important implication of this is that the placebo effect can in principle be used effectively without the placebo itself, through a direct use of autosuggestion.The benefits of such a strategy are clear: fewer side effects from medications, huge cost savings, no deception of patients, relief of burden on the physician's time, and healing in domains where medication or other therapies are problematic.

- by J. Mommaerts and +1
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- Philosophy, Pain, Psychology of Unconscious, Placebo Effect

Over the past two decades, potent and selective analgesics have been developed from endogenous opioid peptides. Glycosylation provides an important means of modulating interaction with biological membranes, which greatly affects the pharmacodynamics and pharmacokinetics of the resulting glycopeptide analogues. Furthermore, manipulation of the membrane affinity allows penetration of cellular barriers that block efficient drug distribution, including the blood-brain barrier. Extremely potent and selective opiate agonists have been developed from endogenous peptides, some of which show great promise as drug candidates.

- by Jean Bidlack
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- Future, Blood brain barrier, Glycosylation, Amino Acid Sequence
- by Theodore Cicero
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- Ethanol, Rats, Naloxone, Luteinizing Hormone

A role for endorphins in the mediation of behavioral reinforcement is suggested by several lines of evidence: (1) injections of Met-or Leu-enkephalin or a degradation-resistant analog may serve as reinforcement for self-administration behavior; *. (2) electrical stimulation of many enkephalin-rich regions supports high rates of self-stimulation; * * li and (3) such brain stimulation reinforcement may be antagonized in a dose-related fashion by naloxone.'. Thus, results both from self-administration testing (which demonstrates reinforcement from exogenously administered endorphins) and from self-stimulation testing (which demonstrates reinforcement from endogenously released endorphins) are consistent with the hypothesis that brain endorphins may regulate or 22 1

- by James Belluzzi
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- Multidisciplinary, Memory, Morphine, Rats
- by Victor Hruby is to
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- Chemistry, Drug Design, Structure activity Relationship, Endorphins

Lesavant ages de la pratique d'une activité physique sont maintenant reconnus tant du point de vue physiologique que du point de vue psychologique. L'activité physique réduit en effet les risques de mort prématuré de certaines maladies cardiovasculaires (par exemple infarctus du myocarde, hypertension artérielle, accident vasculaire cérébral), du diabète de type II et du cancer du colon. Outre son pouvoir sur le bien-être psychologique, l'activité physique aide à contrôler le poids, réduit l'hypertension artérielle, et améliore le fonctionnement

- by Margarida de Matos
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- Anxiety Disorders, Depression, Self Efficacy, Brain
- by George B Stefano
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- Cognitive Science, Invertebrates, Neurons, Time Factors

Psychological factors have an important influence on pain perception. Both in the clinic and in experimental settings, distraction has been shown to reduce pain. Further, negative emotions increase pain, whereas positive emotions have the opposite effect. Other more complex psychological states alter the way we feel pain. For instance, empathy for another person who is suffering increases our own pain experience, and expectation of pain relief underlies much of the placebo effect. Neuroimaging studies show a physiological basis for psychological pain modulation, with activity in pain pathways altered by attentional state, positive and negative emotions, empathy and the administration of a placebo. The same psychological factors activate intrinsic modulatory systems in the brain, including those stimulated when opiates are given for pain relief. It is important for the dentist and patients to understand the influence of psychological state on pain transmission. Such an understanding ...

- by Petra Schweinhardt
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- Dentistry, Pain, Attention, Placebo Effect

It is known for a long time that exercise increases physical adequacy, has beneficial effects on the general health condition as well as a playing preventing role against various disease states. To decrease the risk of disease and maintain good health, the natural defense system of the organism needs to be strengthened. It is thought that in addition to increasing the body's resistance to disease through the strengthening of the immune system, decreases the convalescence time, increases work efficiency and improves the sportive performance of the individual all which would contribute positively to the national economy. The positive effects of regular exercising of aerobic nature such as strengthening of the immune system, protection against diseases as well as its positive effects on quality of life will help to emphasize the importance of physical exercise and improve the general view of sports by society.

- by Kursat Karacabey
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- Mental Health, Health, Osteoarthritis, Osteoporosis
- by Joe Herbert
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- Reproduction, Multidisciplinary, Mammals, Melatonin

in the elderly. NEUROBIOL AGING 9(1) 9-16, 1988.--Weight loss and anorexia occur commonly in the elderly. While in many cases the anorexia can be attributed to associated disease processes, it does appear that a true anorexia of aging exists. Animal studies have suggested that older rodents have an excessive satiety effect of cholecystokinin and a decreased opioid feeding drive. Other older persons develop anorexia in association with depression. In these subjects, excess corticotropin-releasing factor may be the neurotransmitter involved in the pathogenesis of the anorexia. In Alzheimer's disease, decreases in norepinephrine and neuropeptide Y may be involved in the anorexia seen in the these patients.

- by John Morley
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- Eating Disorders, Aging, Food, Taste
- by gennaro marino
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- Physiology, Peptides, Arthropods, Radioligand Assay

Using the recent burgeoning of information on how the stress response systems interact, and combining this with advances in our understanding of neuroimmune communication, a proposed neuroendocrine-neuroimmune stress response system incorporating autoimmunoregulation is reviewed. The study of immunocyte behavior in certain clinical conditions associated with a variant stress response may help illuminate the functioning of the neuroendocrine-neuroimmune stress response system.

- by George B Stefano
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- Depression, Cytokines, Stress, Corticotropin Releasing Hormone

Matched hypothalamo-pituitary portal and jugular blood samples were collected over about 6 h from 7 lactating Corriedale ewes penned with their lambs, and a careful record was kept of ewe/lamb behaviour. Hypothalamo-pituitary portal blood concentrations of beta-endorphin were measured by radioimmunoassay and the secretion rates were calculated; these were related to peripheral plasma prolactin and LH concentrations, and the sucking bouts of the lambs. Basal LH concentrations remained less than 1 ng/ml with 0-2 pulses of 1.5-3.5 ng/ml amplitude per 6-h collection period. Prolactin secretion was episodic with individual baselines varying from 24 to 286 ng/ml, and peak concentrations of 50-631 ng/ml. Portal beta-endorphin was secreted in an episodic pattern with individual baseline secretion rates varying from 0.125 to 0.495 ng/min, and peak secretion rates of 0.768 to 3.216 ng/min. A close correlation was seen between sucking bouts and the secretion of portal beta-endorphin and periph...

- by Marilyn Renfree
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- Physiology, Reproduction, Lactation, Pregnancy

Work over the past decade has supported the idea that discrete aspects of appetitive motivation are differentially mediated by separate but interacting neurochemical systems within the nucleus accumbens (Acb). We review herein a series of studies in rats comparing the effects of manipulating Acb amino acid, opioid, acetylcholine, and dopamine systems on tests of free-feeding and food-reinforced operant responding. Results from our laboratory and in the literature support three general conclusions: (1) GABA output neurons localized exclusively within the Acb shell directly influence hypothalamic effector mechanisms for feeding motor patterns, but do not participate in the execution of more complex food-seeking strategies; (2) enkephalinergic neurons distributed throughout the Acb and caudate-putamen mediate the hedonic impact of palatable (high sugar/fat) foods, and these neurons are under modulatory control by striatal cholinergic interneurons; and (3) dopamine transmission in the Acb governs general motoric and arousal processes related to response selection and invigoration, as well as motor learning-related plasticity. These dissociations may reflect the manner in which these neurochemical systems differentially access pallido-thalamo-cortical loops reaching the voluntary motor system (in the case of opioids and dopamine), versus more restricted efferent connections to hypothalamic motor/autonomic control columns (in the case of Acb shell GABA and glutamate systems). Moreover, we hypothesize that while these systems work in tandem to coordinate the anticipatory and consummatory phases of feeding with hypothalamic energy-sensing substrates, the striatal opioid network evolved a specialized capacity to promote overeating of energy-dense foods beyond acute homeostatic needs, to ensure an energy reserve for potential future famine. D

- by Wayne Pratt
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- Motor Learning, Food, Energy Metabolism, Nucleus Accumbens

Das Potenzial des analgetischen Plazeboeff ektes S3-Leitlinien-Empfehlung zur Behandlung akuter und perioperativer Schmerzen S3-Leitlinie der AWMF Die Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF) hat im Mai 2007 die S3-Leitlinie zur "Behandlung akuter und perioperativer Schmerzen" herausgegeben und sie im April 2009 aktualisiert. Mit Empfehlung der AWMF-Leitlinie hat der Plazeboeff ekt offi ziellen Eingang in die klinische Versorgung gefunden (q Tab. 1). ▶ Es ist wichtig hervorzuheben, dass der Einsatz von Plazebos nicht gleichzusetzen ist mit einer verfügbaren aktiven Schmerztherapie. Es ist ethisch nicht vertretbar, Patienten Plazebos zu verabreichen, wenn sie nicht darüber informiert und aufgeklärt wurden und wenn eine aktive Schmerztherapie möglich ist. Plazeboeff ekte sollten jedoch im Rahmen der medikamentösen oder psychologischen Schmerztherapie durchaus genutzt werden und sind als Additiv zu verstehen (q Abb. 1). Jedes wirksame Schmerzmedikament bzw. jede wirksame Schmerztherapie kann über die rein pharmakologische Wirkung hinaus durch Plazebos optimiert werden. Plazebo-und Nozeboeff ekte Unter einem Plazeboeff ekt versteht man eine positive Veränderung im Körper aufgrund einer symbolischen Bedeutung, die einem Ereignis oder einem Objekt in einem heilenden Kontext zugeschrieben wird [2]. Grundsätzlich ist der Plazeboeff ekt damit nicht auf den Einsatz von Substanzen beschränkt. ▶ Klassischerweise spricht man von analgetischen Plazeboeff ekten, wenn ein akuter oder chronischer Schmerz nach Gabe pharmakologisch wirkstoffl oser Substanzen (im Labor oder im Rahmen von klinischen Prüfungen) reduziert wird. Plazeboeff ekte können aber auch im Kontext eines pharmakologisch wirkungsvollen Analgetikums oder einer anderweitigen schmerztherapeutischen Behandlung additiv das Wirkspektrum erhöhen. ▶ Analog werden auch nicht spezifi sche und unerwünschte Wirkungen bzw. Nebenwirkungen eines Verums durch ein wirkstoff freies Agens ausgelöst. In diesen Fällen spricht man vom sog. Nozeboeff ekt. Eine Hyperalgesie lässt sich genauso wie eine verminderte Schmerzempfi ndlichkeit experimentell erzeugen und scheint auch vergleichbaren Regeln zu folgen [3]. Die zugrunde liegenden biologischen Mechanismen ihrer Vermittlung sind vermutlich unterschiedlich [4]. Die S3-Leitlinie der AWMF zur "Behandlung akuter und perioperativer Schmerzen" empfi ehlt für diesen Bereich erstmals, Plazeboeff ekte klinisch zu nutzen und Nozeboeff ekte zu vermeiden. Eff ektivität von Plazebos Bestimmte Merkmale, die für die Eff ektivität von Plazebos untersucht und beschrieben wurden, zeigen q Tab. 2, q Tab. 3 [5-10]. Am besten wirken z. B. Plazebos, Regine Klinger Der Plazeboeff ekt ist seit jeher von Mystik und eher negativen Konnotationen umgeben. Erst in den letzten Jahren rückte insbesondere der analgetische Plazeboeff ekt durch viele empirische Wirksamkeitsnachweise in ein deutlich positiveres Licht. Diese Wende spiegelt sich auch in der neuen S3-Leitlinie der AWMF zur Behandlung akuter und perioperativer Schmerzen wider [1]. Sie empfi ehlt, den Plazeboeff ekt klinisch zu nutzen. In diesem Beitrag werden Wirkmechanismen und Wirksamkeitsnachweise des analgetischen Plazeboeff ektes auf empirischer, psychologischer und psychobiologischer Ebene beschrieben. Es wird diskutiert, wie der Plazeboeff ekt im Akut-und auch chronischen Schmerzmanagement nutzbringend eingesetzt werden kann. 22 Klinger R. Das Potenzial des analgetischen Plazeboeff ektes -S3-Leitlinien-Empfehlung ... Anästhesiol Intensivmed Notfallmed Schmerzther 2009; 45: 22-29 Fachwissen S Glossar AWMF Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V. CCK Cholecystokinin, ein antiopioides Peptid FMRI funktionelle Magnetresonanztomografi e PET Positronen-Emissions-Tomografi e rACC "rostral anterior cingulated cortex" Heruntergeladen von: Universitätsklinikum Hamburg-Eppendorf. Urheberrechtlich geschützt.

- by Regine Klinger
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- Placebo Effect, Placebos, Postoperative pain, Endorphins

Recent studies have suggested that the tridecapeptide, neurotensin, may be an endogenous satiety factor. The present study was undertaken to examine the effects of neurotensin on multiple paradigms known to stimulate feeding. Following a 30 hour starvation period, neurotensin suppressed feeding at the 20 microgram and 10 microgram dose, but not at the 1 microgram dose when compared to saline controls. Norepinephrine (20 micrograms ICV) induced feeding was suppressed at the 20 microgram neurotensin dose but not at the 10 microgram or 1 microgram dose. In contrast, neurotensin did not suppress muscimol induced feeding at any of the doses. Insulin induced feeding (10 units SC) also was not suppressed by neurotensin. Neurotensin suppressed dynorphin induced feeding at the 20 microgram and 10 microgram but not at the 1 microgram dose. Neurotensin suppressed spontaneous feeding (p less than 0.01) in vagotomized rats (2.5 +/- 0.3 g/2 hr) when compared with saline controls (4.2 +/- 0.5 g/2 ...

- by John Morley
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- Insulin, Feeding Behavior, Dynorphins, Rats

Synthetic genes for human insulin A and B chains were cloned separately in plasmid pBR322. The cloned synthetic genes were then fused to an Escherichia coli #-galactosidase gene to provide efficient transcription and translation and a stable precursor protein. The insulin peptides were cleaved from Pgalactosidase, detected by radioimmunoassay and purified. Complete purification of the A chain and partiaf purification of the B chain were achieved. These products were mixed, reduced, and reoxidized. The presence of insulin was detected by radioimmunoassay.

- by H. Heyneker and +1
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- Genetics, Science, Multidisciplinary, Recombinant DNA Technology

Four cyclic enkephalin analogues and four cyclic dermorphin analogues have been synthesized. Cyclization of linear peptides containing basic amino acid residues of various side chain length in position 2 and 5 (enkephalin analogues) or 2 and 4 (dermorphin analogues) was achieved by treatment with bis-(4-nitrophenyl) carbonate to form a urea unit. The peptides were tested in the guinea-pig ileum (GPI) and mouse vas deferens (MVD) assays. Diverse activity was observed, depending on the size of the ring and the location of the urea unit. The conformation of two dermorphin analogues has been studied: one of high activity (IC 50 = 4.15 nM in the GPI assay) and a second of low activity (IC 50 = 6700 nM in the GPI assay). The conformational space of these peptides was examined using the EDMC method. Using data from the NMR spectra, each peptide was described as an ensemble of conformers. Biological activity was discussed in light of the structural data.

- by Katarzyna Filip
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- Peptide Science, Magnetic Resonance Spectroscopy, Cyclic peptides, Peptide

Considerable research has been focused in identifying biochemical changes in biological tissues and fluids which may be specifically associated with the occurrence of headaches, in particular migraine (MI) and cluster headaches (CH). 1-4 Whereas most of this work has been directed to elucidate the possible role of vasoactive substances in the etiology of these conditions, 1-4 more recently some interest has shifted towards a better understanding of the mechanisms involved in the abnormal modulation of the pain response observed in these patients. 5-23

- by Frederick Freitag
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- Medicine, Headache, The, Clinical Sciences

Primate societies are characterized by bonded social relationships of a kind that are rare in other mammal taxa. These bonded relationships, which provide the basis for coalitions, are underpinned by an endorphin mechanism mediated by social grooming. However, bonded relationships of this kind impose constraints on the size of social groups that are possible. When ecological pressures have demanded larger groups, primates have had to evolve new mechanisms to facilitate bonding. This has involved increasing the size of vocal and visual communication repertoires, increasing the time devoted to social interaction and developing a capacity to manage two-tier social relationships (strong and weak ties). I consider the implications of these constraints for the evolution of human social communities and argue that laughter was an early evolutionary innovation that helped bridge the bonding gap between the group sizes characteristic of chimpanzees and australopithecines and those in later ho...

- by robin dunbar
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- Laughter, Ecology, Animal communication, Biological Sciences
- by Stan Watson
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- Life Sciences, Dexamethasone, Depressive Disorder, Psychotic Disorders

H spectra a t 270 MHz of zwitterionic Met-enkephalin pentapeptide (Tyr-Gly-Gly-Phe-Met) in (C2H3)2SO/ water mixtures are reported and discussed in terms of solvent-induced conformational transitions. The analysis of the chemical shifts, line widths, coupling constants and rotamer populations around 1' and z2 suggests that the conformational properties of Met-enkephalin in the two solvents are quite different. In aqueous solution, the preferred structure, characterized by the absence of intramolecularly hydrogen-bonded NH groups and head-to-tail interactions, very likely is an equilibrium of unfolded conformations with approximately equal energy. In (C2H3)2S0, the preferred structure is folded, with the Met-5 NH intramolecularly bonded and the Gly-3 NH protected from the solvent, while the Gly-2 and Phe-4 amide protons are solvent exposed. A conformational transition of Met-enkephalin from the intramolecularly bonded to the unbonded one takes place at about 40 mol-% water in (C2H3)2S0, involving the Met-5 N H proton and the Tyr-Gly-Gly fragment. The Phe-4 and Met-5 4 angles do not change appreciably, which suggests that an inversion at the Gly-3 residue of the folded form, responsible for the conformational transition, does not affect the C-terminal moiety. At about 70 m o l-x water in (C2H3)2S0 a change in the solvent mixture properties affects the x' rotamer populations and the ring dynamics of the aromatic side chains. The line broadening of the Tyr-I 6 and E proton resonances indicates a specific interaction of the N-terminal ring with the solvent.

- by Roberto Tomatis
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- Water, Nuclear Magnetic Resonance, Magnetic Resonance Spectroscopy, Temperature

The effect of endogenous opioid peptides (EOP) on LH secretion is variable during different physiological states. A series of experiments concerning the role of EOP on LH secretion in cyclic gilts was performed. They were comprised of (1) an administration of an opioid antagonist or agonist in gilts during the estrous cycle and in ovariectomized (OVX) gilts in which the LH surge was induced with estradiol benzoate (EB) and (2) in vitro studies on GnRH release from the stalk median eminence (SME) of cyclic gilts and OVX estrogen and progesterone primed gilts in response to naloxone (NAL). Naloxone and met-enkephalin analogue (FK 33-824) administration as a single independent injections did not affect LH secretion during the early (Day 16) or late (Day 19 or 20) follicular phase. However, continuous infusion of FK 33-824 for 4 h decreased LH secretion during the infusion period on Day 19 of the estrous cycle. Morphine also exerts an inhibitory effect on the EB-induced LH surge during ...

- by Hanna Kalamarz-Kubiak
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- Swine, Naloxone, Luteinizing Hormone, Endorphins

The endocrine stress response is pivotal in vertebrate physiology. The stress hormone cortisol-the end product of the endocrine stress axis-(re-)directs energy flows for optimal performance under conditions where homeostasis may be or become at risk. Key players in the continuous adaptation process are corticotropin-releasing factor (CRF) from the hypothalamic nucleus preopticus (NPO), pituitary adrenocorticotropic hormone (ACTH) and cortisol produced by the interrenal cells in the headkidney (adrenal equivalent of fish). CRF is a member of a large family of related peptides that signals through CRF-receptor subtypes specific for central and peripheral actions of the peptide. CRF is ''chaperoned'' by a unique and phylogenetically very well-conserved binding protein (CRFBP); the functions of the CRFBP can only be speculated on so far, but its mRNA and protein abundance are important indicators of the central CRFsystem activity, and indeed its mRNA levels are altered by restraint stress. Moreover, the unique structure and size of the CRFBP provide good tools in phylogenetic studies, that date the CRF-system to at least one billion years old. Pro-opiomelanocortin is produced and processed to ACTH and endorphin in the hypothalamic NPO and pituitary pars distalis ACTH-cells, to MSH and acetylated endorphins in the pituitary pars intermedia MSH-cells. ACTH is the prime corticotrope in acute stress conditions. In carp, MSH, considered a mild corticotrope in chronic stress responses in other fish, lacks corticotropic effects (in line with the absence of the melanocortin-5 receptor in headkidney); yet, an unknown corticotropic signal susbtance in the pars intermedia of carp awaits elucidation. Interesting observations were made on the CRF control of pituitary cells. CRF stimulates ACTH-cells, but only when these cells experience a mild dopaminergic block. Endorphin, produced in the NPO and transported via axons to the pituitary gland in vivo, reverses the stimulatory CRF action on MSH-cells to a differential inhibition of N-acetyl b-endorphin release in vitro (MSH release is not affected). We speculate that the consistently observed elevation of plasma MSH during chronic stress may exert central actions related to feeding and leptin regulated processes. A BOLD-fMRI study revealed the functional anatomy of the stress response at work in a paradigm, where carp were exposed to a sudden water temperature drop. In carp (and other fish), the endocrine stress axis is already operational in very early life stages, viz., around hatching and comprises hypothalamic, pituitary, and interrenal signaling to adjust the physiology of the hatchling to its dynamically changing environment. Understanding of stress during early life stages is critical as the consequent rises in cortisol may have long lasting effects on survival and fish quality.

- by Mark Huising and +1
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- Physiology, Zoology, Magnetic Resonance Imaging, Aquaculture

Key words: chronic stress --endogenous opioids --apomorphine --climbing behavior --mouse Mice subjected to repeated stressful experiences showed an increase in stereotypic climbing behavior induced by apomorphine thus suggesting a modified sensitivity of dopaminergic receptors. Naltrexone, injected before each stressful experience, reversed this effect of chronic stress indicating an involvement of endogenous opioids.

- by Stefano Puglisi-Allegra and +1
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- Cognitive Science, Brain, Mice, Dopamine Receptors

- by Kursat Karacabey
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- Mental Health, Health, Osteoarthritis, Osteoporosis

Cannabinoids and opioids both produce analgesia through a G-protein-coupled mechanism that blocks the release of pain-propagating neurotransmitters in the brain and spinal cord. However, high doses of these drugs, which may be required to treat chronic, severe pain, are accompanied by undesirable side effects. Thus, a search for a better analgesic strategy led to the discovery that delta 9-tetrahydrocannabinol (THC), the major psychoactive constituent of marijuana, enhances the potency of opioids such as morphine in animal models. In addition, studies have determined that the analgesic effect of THC is, at least in part, mediated through delta and kappa opioid receptors, indicating an intimate connection between cannabinoid and opioid signaling pathways in the modulation of pain perception. A host of behavioral and molecular experiments have been performed to elucidate the role of opioid receptors in cannabinoid-induced analgesia, and some of these findings are presented below. The aim of such studies is to develop a novel analgesic regimen using low dose combinations of cannabinoids and opioids to effectively treat acute and chronic pain, especially pain that may be resistant to opioids alone. D

- by Sachin Patel
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- Life Sciences, Neuropsychopharmacology, Cannabinoids, Animal Model

Post-tetanic events were recorded in isolated, superfused, epididymal and prostatic halves of the rat vas deferens. Increasing the frequency of nerve stimulation from 0.15 to 15 Hz (1 30 s) and then back to 0.15 Hz produced a post-tetanic potentiation (PTP) of the muscular responses in the epididymal end but a posttetanic inhibitory response (PTI) in the prostatic half. Both efl'ects were abolished by tetrodotoxin or animal pretreatment with 6-hydroxy dopamine (6-OHDA). PTP was markedly reduced by reserpine treatment or tissue incubation with prazosin. PTI was not altered by adrenergic drugs but partially reduced by tissue application of bicuculline or strychnine, revealing that 7-aminobutyric acid (GABA) may modulate the motor transmission towards the prostatic half of the rat ductus.

- by Jaime Montiel
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- Psychology, Cognitive Science, Biology, Medicine
- by Eric Bittman
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- Cognitive Science, Biology, Medicine, Brain

LeujEnkephalin (400.0 ;tg/kg) and the enkephalin analog [DAlaDLeulenkephalin (0.4, 4.0, and 40.0 ;tg/kg) were intraperitoneally administered to rats 5 min before they were trained on aversively motivated tasks. The peptides impaired acquisition of a one-way active avoidance response, facilitated acquisition of an inhibitory avoidance response, and had no effect on acquisition of a swim-escape response. The data indicate that the enkephalin effects are not mediated through actions on locomotor activity, pain perception or reactivity, or

- by rita messing
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- Perception, Water, Animal Behavior, Pain

ERSPAMER, V., P. MELCHIORRI, M. BROCCARDO, G. FALCONIERI ERSPAMER, P. FALASCHI, G. IMPROTA, L. NEGRI AND T. RENDA. The brain-gut-skin triangle: New peptides. PEPTIDES 2: Suppl. 2, 7-16, 1981.--New data on tachykinins and bombesins are displayed and the present situation of research on the novel amphibian skin peptides sauvagine and dermorphin is illustrated. The potent stimulant effect of sauvagine on ACTH and//-endorphin release has been confirmed both in vivo and on columns of isolated and dispersed rat pituitary cells, and similarly the potent inhibitory effect on PRL and GH release, both in the rat and man. Particular emphasis is laid on the occurrence of sauvagine-like immunoreactivity in fish urophysis and in amphibian nervous structures, including the retina. It is suggested that the long-searched corticotropin releasing factor and PRL release-inhibiting factor may be a sauvagine-like peptide. Dermorphin, in its turn, has been found to cause, by intracerebroventricular injection, not only analgesia and catalepsy, but also conspicuous EEG and behavioral changes in the rabbit and chick, as well as a sharp reduction in gastric emptying time and gastric acid output in the rat, together with marked stimulation of PRL release.

- by L. Negri
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- Physiology, Animal Behavior, Brain, Prolactin
- by Pravesh Verma
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- Cognitive Science, Behavior, Serotonin, Dopamine