Thesis (M.A.)--Baylor University, 2009. / Includes bibliographical references (p. 44-55).

Thesis (PhD) - Swinburne University of Technology, Brain Sciences Institute, 2008. / A thesis submitted for the degree of Doctorate of Philosophy, Brain Sciences Institute, Swinburne University of Technology - 2008. Typescript. Includes bibliographical references (p. 98-133)

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.

Many human pharmaceuticals have limited biodegradability and can end up in the aquatic environment. The effects of these pharmaceuticals on aquatic organisms is not fully understood. Ropinirole is a drug used to treat Parkinson’s disease. Ropinirole is a dopamine agonist that targets the dopaminergic system that many diverse organisms share. In this study, threespined sticklebacks (Gasterosteus aculeatus) were used to investigate the effect of ropinirole on wild animals. Wild captured sticklebacks were exposed to ropinirole, ropinirole and fluoxetine, or untreated control. The fish were sacrificed at two different time points to study the effects on gene expression after long and short- time exposure of the drug. Gene expression of two dopamine receptor genes (drd2 and drd1b) and one adrenergic receptor gene (adrd2a) is studied in this project. The fish brains were dissected, total mRNA isolated and translated to cDNA, and finally qPCR was done. The expression of drd2 and adrd2a genes did not differ across the treatment groups or time. Drd1b showed higher expression at long term of exposure relative to short time exposure to ropinirole, but no other differences were observed between treatment groups. Collectively, my results show that ropinirole, or ropinirole together with fluoxetine did not interact with the adrenergic receptor or the dopamine 2-receptor. Exposure to ropinirole longer time can upregulate genes, as seem for the gene drd1b.  Overall, these results show that pharmaceuticals in the environment can affect gene expression on other animals than the targeted humans.

abstract: The thrill of a live performance can enhance endorphin, serotonin, dopamine, and adrenaline levels in the body. This mixture of heightened chemical levels is a result of "performance adrenaline." This phenomenon can positively and/or negatively affect a performing singer. A singer's body is her instrument, and therefore, any bodily change can alter the singing voice. The uptake of these chemicals can especially influence a central aspect of singing: breath. "Performance adrenaline" can induce shallow or clavicular breathing, alter phonation, and affect vibrato. To optimize the positive effects and counteract the negative, diaphragmatic breathing, yoga, and beta-blockers are explored as viable management tools. When managed properly, the boost offered by "performance adrenaline" can aid the singer in performing and singing. After a review of medical and psychological studies that reveal the physiological and emotional effects of endorphins, serotonin, dopamine, and adrenaline, this paper will explore the biological changes specific to vocalists and methods to optimize these effects in performance. / Dissertation/Thesis / Doctoral Dissertation Music 2015

No description available.

abstract: Sensory gating is a process by which the nervous system preferentially admits stimuli that are important for the organism while filtering out those that may be meaningless. An optimal sensory gate cannot be static or inflexible, but rather plastic and informed by past experiences. Learning enables sensory gates to recognize stimuli that are emotionally salient and potentially predictive of positive or negative outcomes essential to survival. Olfaction is the only sensory modality in mammals where sensory inputs bypass conventional thalamic gating before entering higher emotional or cognitive brain regions. Thus, olfactory bulb circuits may have a heavier burden of sensory gating compared to other primary sensory circuits. How do the primary synapses in an olfactory system "learn"' in order to optimally gate or filter sensory stimuli? I hypothesize that centrifugal neuromodulator serotonin serves as a signaling mechanism by which primary olfactory circuits can experience learning informed sensory gating. To test my hypothesis, I conditioned genetically-modified mice using reward or fear olfactory-cued learning paradigms and used pharmacological, electrophysiological, immunohistochemical, and optical imaging approaches to assay changes in serotonin signaling or functional changes in primary olfactory circuits. My results indicate serotonin is a key mediator in the acquisition of olfactory fear memories through the activation of its type 2A receptors in the olfactory bulb. Functionally within the first synaptic relay of olfactory glomeruli, serotonin type 2A receptor activation decreases excitatory glutamatergic drive of olfactory sensory neurons through both presynaptic and postsynaptic mechanisms. I propose that serotonergic signaling decreases excitatory drive, thereby disconnecting olfactory sensory neurons from odor responses once information is learned and its behavioral significance is consolidated. I found that learning induced chronic changes in the density of serotonin fibers and receptors, which persisted in glomeruli encoding the conditioning odor. Such persistent changes could represent a sensory gate stabilized by memory. I hypothesize this ensures that the glomerulus encoding meaningful odors are much more sensitive to future serotonin signaling as such arousal cues arrive from centrifugal pathways originating in the dorsal raphe nucleus. The results advocate that a simple associative memory trace can be formed at primary sensory synapses to facilitate optimal sensory gating in mammalian olfaction. / Dissertation/Thesis / Ph.D. Biology 2012

abstract: 5-HT2A receptor (R) antagonists and 5-HT2CR agonists attenuate reinstatement of cocaine-seeking behavior (i.e., incentive motivation). 5-HT2Rs are distributed throughout the brain, primarily in regions involved in reward circuitry, including the prefrontal cortex (PFC), caudate putamen (CPu), and basolateral (BlA) and central (CeA) amygdala. Using animal models, we tested our hypotheses that 5-HT2ARs in the medial (m) PFC mediate the incentive motivational effects of cocaine and cocaine-paired cues; 5-HT2ARs and 5-HT2CRs interact to attenuate cocaine hyperlocomotion and functional neuronal activation (i.e, Fos protein); and 5-HT2CRs in the BlA mediate the incentive motivational effects of cocaine-paired cues and anxiety-like behavior, while 5-HT2CRs in the CeA mediate the incentive motivational effects of cocaine. In chapter 2, we infused M100907, a selective 5-HT2AR antagonist, directly into the mPFC and examined its effects on reinstatement of cocaine-seeking behavior. We found that M100907 in the mPFC dose- dependently attenuated cue-primed reinstatement, without affecting cocaine-primed reinstatement, cue-primed reinstatement of sucrose-seeking behavior, or locomotor activity. In chapter 3, we used subthreshold doses of M100907 and MK212, a 5-HT2CR agonist, to investigate whether these compounds interact to attenuate cocaine hyperlocomotion and Fos protein expression. Only the drug combination attenuated cocaine hyperlocomotion and cocaine-induced Fos expression in the CPu, but had no effect on spontaneous locomotion. Finally, in chapter 4 we investigated the effects of a 5- HT2CR agonist in the BlA and CeA on cocaine-seeking behavior and anxiety-like behavior. We found that CP809101, a selective 5-HT2CR agonist, infused into the BlA increased anxiety-like behavior on the elevated plus maze (EPM), but failed to alter cocaine-seeking behavior. CP809101 infused into the CeA attenuated cocaine-primed reinstatement and this effect was blocked by co-administration of a 5-HT2CR antagonist. Together, these results suggest that 5-HT2ARs in the mPFC are involved in cue-primed reinstatement, 5-HT2A and 5-HT2CRs may interact in the nigrostriatal pathway to attenuate cocaine hyperlocomotion and Fos expression, and 5-HT2CRs are involved in anxiety-like behavior in the BlA and cocaine-primed reinstatement in the CeA. Our findings add to the literature on the localization of 5-HT2AR antagonist and 5-HT2CR agonist effects, and suggest a potential treatment mechanism via concurrent 5-HT2AR antagonism and 5-HT2CR agonism. / Dissertation/Thesis / Ph.D. Psychology 2013

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-03-28T12:35:23Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação_Manuella da Luz D Barros.pdf: 1660746 bytes, checksum: 1cd53d223f6d92ef7dab1a2d30b49ece (MD5) / Made available in DSpace on 2017-03-28T12:35:23Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação_Manuella da Luz D Barros.pdf: 1660746 bytes, checksum: 1cd53d223f6d92ef7dab1a2d30b49ece (MD5) Previous issue date: 2016-02-23 / FACEPE / CNPQ / A plasticidade fenotípica compreende a capacidade do organismo de elaborar adaptações morfofuncionais em resposta aos estímulos ambientais. Essa capacidade é mais intensa durante a gestação e lactação (plasticidade do desenvolvimento), podendo estar associada a consequências ao longo da vida. Neste contexto, a serotonina (5-HT) tem papel determinante no desenvolvimento do sistema nervoso central. Além disso, a 5-HT participa do controle central homeostático do balanço energético no núcleo arqueado (Arc) do hipotálamo, estimulando a saciedade e o gasto de energia através da inibição de neurônios orexígenos e estimulação de neurônios anorexígenos via receptores 5-HT1B e 5-HT2C, respectivamente. Dessa forma, a alteração da atividade serotoninérgica durante o desenvolvimento pode modificar a regulação e a expressão do comportamento alimentar em longo prazo. Estudos prévios de nosso grupo de pesquisa apontaram que a inibição seletiva neonatal da recaptação de serotonina (ISNRS) pode estar associada a fenótipo hipofágico na vida adulta. Nós acreditamos que esse fenótipo se deve a maior atividade da via anorexígena no Arc. Diante disso, este estudo teve como objetivo avaliar os efeitos da ISNRS sobre o peso corporal, o comportamento alimentar e a atividade neuronal no Arc em resposta aos agonistas dos receptores 5HT2C e 5-HT1B em ratos adultos. Ratos Wistar foram tratados com solução salina (SAL, n=15) ou fluoxetina (FLUO, n=15) do 1° ao 21° dia pós-natal. Aos 170 dias de vida foi realizada cirurgia de estereotaxia para implantação de cânula no ventrículo lateral direito através da qual foram feitas as injeções intracerebroventricular (ICV). Aos 180 dias foi realizada a pesagem dos animais seguida de injeção ICV de ACSF, agonista do receptor 5-HT2C ou agonista do receptor 5-HT1B, obtendo-se seis grupos experimentais (n=5 animais/grupo): SAL+ACSF, SAL+AG.1B, SAL+AG.2C, FLUO+ACSF, FLUO+AG.1B e FLUO+AG.2C. A partir desses grupos, foi analisada a sequência comportamental de saciedade (SCS) e o número de células reativas contra proteína c-fos no Arc. Comparado ao grupo SAL, o grupo FLUO apresentou menor peso corporal. A ISNRS também promoveu maior ingestão alimentar frente ao estímulo com o agonista 5-HT2C, menor taxa alimentar após injeção de ACSF e antecipação do ponto de saciedade após estímulo com o agonista 5-HT1B. Além disso, o grupo FLUO apresentou maior número de células reativas contra c-fos no Arc frente ao agonista 5-HT2C. Corroborando nossa hipótese, a ISNRS parece promover aumento da atividade da via anorexígena no Arc na idade adulta, apesar de não ter ocorrido redução da ingestão alimentar. Em conjunto, os achados deste estudo sugerem que o menor peso corporal em ratos adultos submetidos à ISNRS pode ser consequência do aumento da atividade da via anorexígena no Arc, o que pode contribuir para um aumento do gasto energético. / Phenotypic plasticity comprises the ability of an organism to develop morphological and functional adaptations in response to environmental stimuli. This capacity is more intense during pregnancy and lactation (developmental plasticity) and may be associated with consequences throughout life. In this context, serotonin (5-HT) has a decisive role in the development of the central nervous system. Furthermore, 5-HT participates in homeostatic central control of energy balance in the arcuate nucleus (Arc) of the hypothalamus, stimulating satiety and energy expenditure through inhibition of orexigenic neurons and stimulation anorectic neurons via 5-HT1B receptors and 5-HT2C, respectively. Thus, the modification of serotonergic activity during development can change the regulation and expression of feeding behavior in the long term. Previous studies from our research group showed that neonatal selective serotonin reuptake inhibition (NSSRI) may be associated with hypophagic phenotype in adulthood. We believe that this phenotype is due to increased activity of anorectic via in the Arc. Thus, this study aimed to evaluate the effects of NSSRI on body weight, feeding behavior and neuronal activity in the Arc in response to 5-HT2C and 5-HT1B receptors agonists in adult rats. Wistar rats were treated with saline (SAL, n=15) or fluoxetine (FLUO, n=15) from 1° to 21° postnatal day. At 170 days, stereotactic surgery was performed for implantation of a cannula in the right lateral ventricle through which were made the intracerebroventricular injections (ICV). At 180 days, weighing of animals was performed followed by ICV injections of ACSF, 5-HT2C or 5-HT1B receptors agonists, resulting in six experimental groups (n=5 animals/group): SAL+ACSF, SAL+AG.1B, SAL+AG.2C, FLUO+ACSF, FLUO+AG.1B and FLUO+AG.2C. From these groups, behavioral satiety sequence (SCS) and number of reactive cells against c-fos protein in the Arc were analyzed. Compared to the SAL group, FLUO group had lower body weight. NSSRI also promoted greater food intake after stimulation with 5-HT2C receptor agonist, lower feed rate after injection of ACSF and anticipation of the point of satiety after stimulation with 5-HT1B receptor agonist. Furthermore, FLUO group had a higher number of reactive cells against c-fos in the Arc after stimulation with 5-HT2C receptor agonist. Corroborating our hypothesis, NSSRI seems to promote increased anorexigenic pathway activity in the Arc in adulthood, despite not having been reduced food intake. Together, the findings suggest that lower body weight in adult rats submitted to NSSRI may be a consequence of increased anorexigenic pathway activity in the Arc, which can contribute to an increase in energy expenditure.

Analisamos o efeito do sistema serotoninérgico no desenvolvimento somático e na ontogênese de reflexos dos filhotes, cujas mães foram submetidas a tratamento farmacológico durante a prenhez. Ratas wistar prenhas foram divididas em dois grupos (N=11): Grupo AD, tratadas com água destilada, Grupo Sert, tratadas com sertralina 30mg/kg, 0,5mL/100g, s.c. Um dia após o parto 8 neonatos (4 machos e 4 fêmeas) foram mantidos com suas mães do 1º ao 21º dia pós-natal. O investigador cego avaliou o crescimento somático, características físicas e maturação de reflexos. Aos 22 e 60 dias de idade os encéfalos foram processados com técnicas de imunoistoquímica contra 5-HT. O grupo Sert, macho ou fêmea, apresentou atraso no crescimento somático e na maturação de alguns reflexos. A quantidade de neurônios 5-HT-IR foi alterada nos núcleos da rafe nos ratos aos 22 dias de idade, mas não aos 60 dias. A análise da morfometria dos neurônios 5-HT-IR, em ambas as idades estudadas, revelou alterações em sua forma. Os resultados deste estudo demonstram a ação inibitória da serotonina sobre o crescimento somático e desenvolvimento sensório-motor bem como alterações na quantidade e na forma dos neurônios 5-HT em ratos. / The aim of the present study was to investigate the effects of prenatal sertraline exposure on offspring in growth and somatic development and even in the maturation of reflex in rats. Female wistar rats were treated with sertraline (Sert, 30 mg/kg, 0,5 mL/100 g, s.c., N=11) or distilled water (Control, N=11) during the whole pregnancy. After the birth, 8 pups (4 males and 4 females) were kept in each litter during lactation. The blind investigator evaluated indicators of general body growth parameters, somatic maturation and ontogeny of reflex during the period of lactation. The central nervous system alterations were approached by 5-HT-IR using the ABC-DAB-Peroxidase techniques in animals at the 22st and 60st postnatal day. The Sert group, showed reduction on the somatic growth and on the maturation of reflexes. There was reduction in the amount of the 5-HT-IR neurons in the raphe nuclei at the 22st postnatal day, but did not change at the 60st. The morphometric analysis revealed alterations in the shape of these cells at the 22st and 60st postnatal day. An inhibitory action of the 5-HT on the somatic and sensory-motor growth in these rats was also observed. After the lactation period, the amount and shape of the 5-HT neurons were altered.