El enamoramiento implica procesos bioquímicos en los que sustancias como neurotransmisores, neuromoduladores y hormonas  interaccionan con células nerviosas u otros órganos. Al estar enamorados, los niveles de dopamina aumentan generando atención, deseo y motivación en todo lo relacionado al ser amado. La serotonina, por el contrario, se presenta en concentraciones bajas en este estado. La oxitocina, por su parte, entra en juego cuando la demanda de dopamina no se logra suplir y es crucial al entablar relaciones de largo plazo. El entendimiento del mecanismo de la oxitocina en el ser humano es crucial no solo para el conocimiento académico sino también porque brinda luces para el tratamiento de algunos desórdenes psicológicos. / Romantic love involves biochemical processes in which substances such as neurotransmitters, neuromodulators and hormones interact with other nerve cells or organs. When being in love, dopamine levels increases, generating attention, desire and motivation in everything related to the beloved person. Serotonin, however, is present in low levels in this state. When the body does not supply the necessary amount of dopamine, oxytocin is released. Oxytocin is vital in long term relationships. Understanding the mechanism of oxytocin in humans is crucial not only for academic knowledge of the chemistry of love but also because it provides new lights for the treatment of some psychological disorders.

Researchers and lay people alike have long held an interest in understanding the antecedents, mechanisms, and consequences of prosocial behaviours: Acts people behave in ways that benefit others, such as cooperation, altruism, care-giving, empathy, sympathy, and compassion. Numerous lines of inquiry have now documented that acting prosocially carries many benefits for not only the recipient, but also the actor. For instance, acting prosocially attracts social capital, social support, and boosts interpersonal relationships; prosociality also increases one’s well-being, happiness, and has long-term physical and mental health benefits. While much of the past work has focused on the main effects of prosociality on various positive outcomes, one area that has received limited attention is understanding the contextual factors and individual differences that moderate these relationships. In the present thesis, I focus on understanding how socioeconomic status (SES) acts as a moderator of the link between prosociality and numerous positive outcomes. In particular, I examined how prosociality is related to building social networks through weak ties, coping with daily stress, and building interpersonal skills. Across these relationships, I examined how SES moderates the link between prosociality and each outcome. My research was guided by the SES-prosociality paradox: That while the rich have access to far greater resources – and thus the ability to act prosocially – it is the poor that tend to act most generously. I theorized that one reason for this paradox is that people across different SES strata benefit differently from acting prosocially. In particular, I reasoned that the people from lower SES backgrounds will tend to have stronger relationship between prosociality and various positive outcomes than people from higher SES backgrounds. To test this hypothesis, I conducted numerous empirical studies using multiple methods – analysing data from subjective reports via surveys and existing data from social media, running natural experiments, and conducting lab experiments using genetic and pharmacological challenge methods. In Chapters 2 and 3, I found that people who act prosocially tend to attract more weak social ties – this is only true for the relatively poor. In Chapter 4, I tested how empathic traits relate to better coping strategies for both lower and higher SES individuals, and found a complex pattern of differing benefits. Finally, in Chapter 5, I found that intranasal oxytocin improves emotional theory of mind, but only for the low SES individuals.

Oxytocin (OT) plays a key role in the mediation of social and stress behaviors across many species; however, the mechanism is still unclear. The present study investigated the influence of prenatal levels of mesotocin (MT; avian homologue of OT) on postnatal social and stress behavior in Northern bobwhite quail. Experiment one determined endogenous levels of MT during prenatal development using an enzyme-linked immunoassay kit. Experiment two examined the influence of increased MT during prenatal development on chicks' individual recognition ability and stress response to a novel environment. Experiment one showed MT levels increased significantly throughout embryonic development. Experiment two showed significant differences in stress behavior for chicks with increased MT during prenatal development; however, no significant differences were found for social behavior. This study suggests MT serves different functions depending on the stage of embryonic development and that increasing MT levels affects postnatal stress behavior, but not social behavior.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / O exercÃcio fÃsico de varias intensidades influencia vÃrios sistemas fisiolÃgicos como (neuromuscular) promovendo aumento de forÃa e massa muscular, (cardiovascular) induzindo bradicardia de repouso e adaptaÃÃes vasculares, endÃcrino favorecendo a liberaÃÃo de vÃrios hormÃnios hipotalÃmicos e atà mesmo o sistema gastrintestinal. O exercÃcio fÃsico dependendo da intensidade e volume pode levar alteraÃÃes de volemia e isquemia gastrintestinal promovendo alteraÃÃes da motilidade gastrintestinal. O objetivo desse trabalho foi investigar o efeito do exercÃcio fÃsico agudo e crÃnico sobre o esvaziamento gÃstrico de lÃquidos, bem como os possÃveis mecanismos envolvendo o equilÃbrio Ãcido-bÃsico e as vias neuro-humorais em tais eventos. Utilizamos ratos machos wistas pesando entre 180 a 250g. Os protocolos de exercÃcio foram divididos em exercÃcio agudo e crÃnico. O agudo consistiu de nataÃÃo em um tanque coletivo 5/dias/10-40min. ApÃs 48h da ultima sessÃo, os ratos foram submetidos a uma sessÃo aguda de exercÃcio com 5% PC. O exercÃcio crÃnico consistiu de adaptaÃÃo ao meio liquido por 5 dias de nataÃÃo coletiva sem sobrecarga. Quarenta e oito horas apÃs a adaptaÃÃo, dos ratos foram submetidos ao protocolo de exercÃcio de saltos (4x10 intervalo de 30seg, 5dias/semana/4semanas). ApÃs a sessÃo de exercÃcio agudo foram avaliados o EG, gasometria arterial, parÃmetros hemodinÃmicos e mecanismos neurohumorais relacionados aos hormÃnios OT e CCK bem como a expressÃo gÃnica desses hormÃnios em tecidos gastrintestinais. Jà no exercÃcio crÃnico, foram avaliados o esvaziamento gÃstrico, trÃnsito intestinal, complacÃncia gÃstrica e parÃmetros hemodinÃmicos. Observamos que tanto os exercÃcios fÃsicos agudos quanto crÃnico promoveram diminuiÃÃo significativa (p < 0,05) no esvaziamento gÃstrico de lÃquidos. AlÃm disso, o exercÃcio crÃnico aumentou significativamente (p < 0,05) a complacÃncia gÃstrica em relaÃÃo aos ratos sedentÃrios, sem alteraÃÃo no transito intestinal. Em relaÃÃo aos ratos sedentÃrios, os ratos exercÃcio agudo apresentaram quadro de acidose metabÃlica com diminuiÃÃo significativa (p < 0,05) nos valore de pH, [HCO3]. Tal alteraÃÃo no equilÃbrio Ãcido-bÃsico foi prevenido significativamente (p < 0,05) com o prÃtratamento de NaHCO3 500mg/kg v.o, 40min antes do exercÃcio. Observamos ainda que o prÃ-tratamento com antagonista de OT e de CCK preveniu significativamente (p < 0,05) a diminuiÃÃo do esvaziamento gÃstrico induzido por exercÃcio agudo. O exercÃcio agudo diminuiu significativamente (p < 0,05) os valores relativos na expressÃo gÃnica dos hormÃnios OT e ANP no fundo e piloro dos ratos, quando comparados aos ratos sedentÃrios. Por outro lado, observamos que o exercÃcio agudo aumentou significativamente (p < 0,05) os valores da expressÃo gÃnica de CCK no fundo, piloro e duodeno dos ratos quando comparados aos sedentÃrios. O exercÃcio fÃsico agudo quanto crÃnico induziu dismotilidade gÃstrica com diminuiÃÃo do esvaziamento gÃstrico. O prÃtratamento com NaHCO3, Atosibana, Devazepide e Ondansetrona preveniu a diminuiÃÃo do esvaziamento gÃstrico induzido por exercÃcio agudo. Sugerimos que a dismotilidade induzida pelo exercÃcio pode ser influenciada por uma via relacionada a OT, 5-HT e CCK alÃm de sofrer influencia do equilÃbrio acido-bÃsico / &#65279;In the recent years, there is a general consensus on the benefits of regular physical activity on health caliber, prevention and treatment of various chronic diseases besides improving general quality of life. Specifically, physical activity of varied intensities broadly influence vital physiological systems involving the neuromuscular system (promoting increased muscle strength and mass) cardiovascular (induced basal bradycardia at rest), endocrine (favoring the release of several hypothalamic hormones) and even the gastrointestinal system. Published literature report that depending on the intensity and volume of exercise, changes in blood volume may result to associated gastrointestinal ischemia, which would possibly alter gastrointestinal motility. However, the mechanisms involved in altered gastrointestinal motility due to exercise are yet to be fully elucidated. Thus, the objective of this study was to investigate the effect of acute and chronic exercise on gastric emptying of liquids, as well as explain the possible mechanisms involving acid-base balance and subsequent neurohumoral pathways. Male Wistar rats (180 to 250g), were obtained from the vivarium of the Department of Physiology and Pharmacology, University Federal do Ceara. They were initially assigned to adapt to either acute or chronic exercise protocols. The acute exercise protocol adaptation consisted of collective swimming in a bath tub over increasing scale periods over 5 days, with a single and final swim 48hs after the fifth day, with a 5% body weight load so as to exploit the lactate threshold. The chronic exercise protocol consisted of collective swimming in a bath tub over 5 days without a specific time count pattern. Forty-eight hours after this adaptation, they were submitted to exercise protocol jumps (4x10 30sec interval, 5days/week/4weeks). After a session of intense exercise, we evaluated gastric emptying, blood analysis, hemodynamic and neurohumoral mechanisms related to hormones 5-HT, OT and CCK as well as the gene expression of these hormones in gastrointestinal tissues. In chronic exercised animals, we evaluated gastric emptying, intestinal transit, gastric compliance and hemodynamic parameters. We found that both acute and chronic exercise promoted a significant decrease (p <0.05) gastric emptying of liquids. Moreover, chronically exercised rats had significant (p <0.05) increased gastric compliance, when compared to sedentary rats; but no change in the intestinal transit. When compared to sedentary rats, acute exercised mice showed metabolic acidosis with a significant decrease (p <0.05) in pH values due to low bicarbonate. This change in acid-base balance was significantly (p <0.05) prevented with pretreating the animals to an oral dose of NaHCO3 (500mg/kg) 40min before exercise. We also observed that pretreatment with OT antagonist and CCK significantly prevented (p <0.05) the decrease in gastric emptying induced by acute exercise. Acute exercise decreased significantly (p <0.05) values for the gene expression of hormones OT and ANP in the fund and pylorus of the rats, when compared to sedentary rats. On the other hand, we found that acute exercise significantly (p <0.05) increased CCK-gene expression values in the fund, pylorus and duodenum of rats, in comparison to sedentary. Concluding, exercise induced changes in gastric motility in both acute and chronic exercise protocols. The pre-treatment with NaHCO3, Atosibana, and Ondansetron Devazepide prevented the decrease in gastric emptying induced by acute exercise. We suggest that dysmotility induced by exercise may be influenced by a pathway related to oxytocin, serotonin and cholecystokinin, which too have a role in the acid-base homeostasis

Diversos estudos têm demonstrado a participação da ocitocina em promover a interação social presente no comportamento materno, sexual e interpessoal, bem como em processos de memória e aprendizagem. Recentemente, a influência da ocitocina sobre a modulação da percepção da dor também tem sido discutida. Estudos histológicos mostraram a presença de receptores de ocitocina em diferentes áreas cerebrais, como a substância cinzenta periaquedutal, envolvida no controle descendente da dor e o hipocampo, envolvido nos mecanismos de memória e aprendizagem aversiva. Este trabalho teve como objetivo investigar os efeitos centrais da ocitocina intranasal sobre a percepção somatossensorial e a memória da dor em humanos. O estudo foi realizado com 31 voluntários do sexo masculino, possuindo idades entre 18 e 45 anos. Para avaliar a influência da ocitocina sobre a percepção e a memória da dor, grupos placebo (solução salina) e experimental (ocitocina intranasal 24 UI ou 40 UI) foram submetidos a Testes de Quantificação Sensorial- QST, que envolveram a aplicação de estímulos térmicos (frio e calor) e mecânicos, a fim de identificar os limiares de detecção e de dor. A memória da dor percebida foi acessada pela Escala Visual Analógica, apresentada após a administração de ocitocina. Os resultados encontrados foram significativos para o efeito da ocitocina sobre o limiar de detecção mecânico (p<0,05), para o grupo ocitocina 40 UI. Ainda, foi possível observar uma tendência à atenuação da memória, frente ao estímulo doloroso frio (p= 0.09). Os demais testes realizados não apresentaram resultados significativos. Estes dados sugerem que a ocitocina, que também é liberada pelo toque não-nocivo, pode aumentar a percepção do toque cutâneo, favorecendo o estabelecimento de vínculos sociais, que são fortemente modulados pela ocitocina. Entretanto, não influencia na detecção de estímulos térmicos inócuos ou na detecção de dor mecânica e térmica, bem como na memória da dor ao calor e ao frio, apesar da clara tendência a uma possível modulação da memória da dor ao frio, o que sugere que os efeitos centrais da ocitocina podem influenciar seletivamente a memória da dor, dependendo da relevância psicobiológica do estímulo / In addition to its role in childbirth labor and lactation, oxytocin is a well-known neurohormone, having several prosocial effects. Moreover, oxytocin seems to play a significant modulatory role in painful experiences, due to its participation in central and peripheral processing of nociceptive somatosensory information. Histological studies have shown the presence of oxytocin receptors in different brain areas, such as periaqueductal gray matter, involved in descending pain control and the hippocampus, involved in memory mechanisms and aversive learning. This work aimed to investigate the effects of intranasal oxytocin on somatosensory perception and pain memory in humans. The participants were 31 healthy men (ages ranging from 18 to 45 years old). To evaluate the influence of oxytocin on the perception and memory of pain, placebo (saline) and experimental groups (intranasal oxytocin 24 IU or 40 IU) were submitted to QST- Quantitative Sensory Testing, which involved the application of thermal stimuli (cold and heat) and mechanical, in order to identify the thresholds of detection and pain. The memory of perceived pain was accessed by the Visual Analog Scale, presented after the administration of oxytocin. The results were significant for the effect of oxytocin on the mechanical detection threshold (p <0.05) for the oxytocin group 40 IU. The data showed a significant increase in tactile perception in an experimental 40 IU oxytocin group. We suggest that this effect could be the basis for the oxytocin-bonding effect via touch. Also, it was possible to observe a tendency to attenuation of the memory, in front of the cold painful stimulus (p = 0.09). The other tests performed did not present significant results. However, it does not influence the detection of harmless thermal stimuli or the detection of mechanical and thermal pain, as well as the memory of pain to heat and cold, despite the clear tendency to a possible modulation of pain memory to cold, suggesting that the central effects of oxytocin may selectively influence pain memory, depending on the psychobiological relevance of the stimulus

Oxytocin (OT) and vasopressin (AVP) are neuropeptides with diverse effects on social behavior, cognition and stress responses. Recent studies suggest that OT facilitates and responds to affiliative forms of human-animal interaction (HAI). However, previous studies measuring OT and AVP in dogs have been limited to measures from blood or urine, which present concerns related to the invasiveness of sample collection, the potential for matrix interference in immunoassays, and whether samples can be collected at precise time points to assess event-linked endocrine responses. Previous studies from our laboratory validated salivary measures of OT and AVP in dogs, however, it is currently unknown whether these measures respond dynamically to aspects of HAI. Here, we investigated the effects of affiliative forms of HAI on both plasma and salivary OT and AVP in dogs. We employed a within-and between-subjects design with a group of Labrador retrievers and Labrador retriever x golden retriever crosses (23 females, 15 males). Half of the dogs engaged in 10 min of free-form friendly interaction with a human experimenter (HAI condition), and the other half rested quietly in the same environment, without human interaction (control condition). We collected blood and saliva samples before, and immediately following both experimental conditions, and all samples were analyzed using enzyme-linked immunosorbent assays (ELISAs) following previously validated protocols. Dogs participating in HAI exhibited a significant increase in both salivary OT (+ 39%) and plasma OT (+ 5.7%) whereas dogs in the control group did not. Salivary AVP showed no change in the HAI group but increased significantly (+ 33%) in the control group. Plasma AVP decreased significantly following HAI (13%) but did not change across time in the control condition. Within the dogs exposed to HAI, increases in salivary OT, and decreases in plasma AVP, were predicted by the extent of affiliative behavior between the dog and human (indexed by scores from a principal components analysis of social behaviors between the dog and human). Collectively our results suggest that measures of salivary OT and AVP provide useful biomarkers in studies of HAI, and afford a flexible and non-invasive toolkit than can be employed in diverse research contexts.

No description available.

Sepsis is a relatively unknown, but common, condition with high mortality. Sepsis is defined as life-threatening organ dysfunction caused by an excessive immune response in the host as a result of an infection. Sepsis can be caused by many different pathogens, giving a varying symptomatic profile and arise via many different routes of exposure. The pathogenesis of sepsis is very complex and not yet fully understood, but hyperactivation of mainly the innate immune system with consequences such as complement activation, cytokine storm, secretion of reactive oxygen species and endothelial influence are considered central mechanisms that further lead to organ dysfunction with septic shock and possible death. The cause of infection in sepsis can often be treated with early-acting broad-spectrum antibiotics, but there is a lack of treatment for the host response and the hyperactivation of the immune system.  Oxytocin is an endogenous neuropeptide that acts on receptors throughout the body including the nervous system and in certain immune cells. Oxytocin has long been known for its role in childbirth and breastfeeding, where it is also used clinically, and for its importance in behavioral functions such as learning and bonding. Recent research has shown a broader effect of oxytocin such as antioxidant and anti-inflammatory substance. These findings have opened up a new perspective on oxytocin and its potential uses, where treatment for sepsis-induced hyperactivation of the immune system is a suggestion.  The aim of this work is to evaluate, based on the published studies, whether exogenous oxytocin can be used therapeutically in sepsis to limit hyperactivation of the immune system and reduce the risk of organ dysfunction with septic shock and possible death.  The method used in the work is literature search via the database PubMed and further analysis and discussion of six preclinical research articles. All analyzed studies were sepsis induced in rodents, and oxytocin was administered as potential treatment.     The results showed exogenous administration of oxytocin in rodents had the effect of antioxidant, anti-inflammatory substance, tissue protective peptide and that via vagal cholinergic stimulation it can to some extent restore physical parameters affected by sepsis induction such as heart rate, heart rate variation and respiration. Oxytocin also had positive effects on the general condition in these preclinical studies. In conclusion, exogenous administration of oxytocin in sepsis seems to have beneficial effects that can reduce the hyperactivation of the immune system in sepsis and contribute to reduced mortality in the same. / Sepsis är en sjukdom som har skördat oändligt många liv historiskt och gör så än idag. Sjukdomens patofysiologi har två komponenter; infektion och överdrivet inflammatoriskt värdsvar vilket orsakar organdysfunktion. I dagsläget kan infektionen oftast behandlas med antibiotika men det saknas medicinsk behandling mot den inflammatoriska responsen. Världshälsoorganisationen gjorde 2017 sepsis till en global hälsoprioritet och betonade då att det behövs nya behandlingsalternativ. Oxytocin är en endogen neuropeptid med komplex verkan i kroppen. Forskningen har sedan länge bekräftat dess betydelse vid förlossning och amning där den också används kliniskt. På senare tid har forskningen börjat intressera sig för oxytocins övriga fysiologiska effekter. Studier visar på att oxytocin har egenskaper som kan påverka immunologiska reaktioner vilket skulle kunna vara av intresse vid behandling av sepsis. Syftet med detta arbete var att utifrån publicerade studier utvärdera om exogent oxytocin kan användas terapeutiskt vid sepsis för att begränsa hyperaktivering av immunförsvaret och reducera risken för organskador med septisk chock och eventuell död som följd. Metoden som användes i arbetet var litteratursökning via databasen PubMed och vidare analys och diskussion av sex prekliniska forskningsartiklar. Alla studier som analyserades använde exogen administrering av oxytocin i en gnagarmodell. Resultaten visade sammantaget att exogen administrering av oxytocin hos gnagare hade effekt som antioxidant, antiinflammatorisk substans, vävnadsskyddande peptid och att oxytocin till viss del kan återställa fysiska parametrar som påverkas av sepsisinduktion såsom hjärtfrekvensvariation, andning och temperatur. Arbetets slutsats blev att exogen administrering av oxytocin vid sepsis har positiva effekter som kan minska hyperaktivering av immunsystemet och bidra till minskad dödlighet vid densamma.

Beacon is a 73-amino acid peptide encoded by a novel gene in the hypothalamus of Israeli sand rat Psammomys obesus. Reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemical techniques were used to investigate the presence of beacon mRNA and the distribution of beacon-immunoreactivity (irBC) in the hypothalamus of ICR mice. RT-PCR experiments revealed beacon mRNA in the mouse hypothalamus. Using a rabbit polyclonal antiserum directed against the synthetic C-terminal peptide fragment (47-73), irBC was detected in the mouse hypothalamus and pituitary. In the hypothalamus, irBC was concentrated in perikarya of the supraoptic (SO), paraventricular (PVH) and accessory neurosecretory nuclei and in cell processes of the median eminence and pituitary stalk. In the pituitary, irBC was noted mainly in the posterior lobe. Double-labeling the hypothalamic sections with guinea-pig vasopressin-antiserum or mouse monoclonal oxytocin-antibody and beacon-antiserum revealed that <30% of vasopressin-immunoreactive neurons and nearly all oxytocin-immunoreactive neurons in the PVH and SO were irBC. The result shows the presence of beacon mRNA in the mouse hypothalamus, and the distribution of irBC is distinctively different from that reported in the hypothalamus of Psammomys obesus, but similar to that of the Sprague-Dawley rats described in our earlier study. More interestingly, Blast search uncovered a 73-amino acid peptide, human ubiquitin-like 5, which has the same exact sequence as beacon. Thus, irBC observed in the mouse brain could be that of ubiquitin-like 5.

With the use of an antiserum against human apelin-36, apelin-immunoreactivity (irAP) was detected in neurons and cell processes of the supraoptic nucleus (SO), paraventricular nucleus (PVH), accessory neurosecretory nuclei (Acc) and suprachiasmatic nucleus. Strongly labeled cells/processes were noted in the internal layer of the median eminence, infundibular stem, anterior and posterior pituitary. Double-labeling the sections with goat polyclonal neurophysin I-antiserum and rabbit polyclonal apelin-antiserum revealed a population of magnocellular neurons in the PVH, SO and Acc expressing both irAP and neurophysin I-immunoreactivity (irNP), the latter being a marker of oxytocin-containing neurons. By inference, the AP-positive but irNP-negative magnocellular neurons could be vasopressin-containing. The presence of irAP in certain hypothalamic nuclei and pituitary suggests that the peptide may be a signaling molecule released from the hypothalamic-hypophysial axis.