O Hormônio Concentrador de Melanina (MCH) está associado ao controle da ingestão de alimentos, peso corporal e homeostase da energia. Além disso, a lactação é um modelo fisiológico importante para estudar a integração do hipotálamo com os sinais sensoriais periféricos, como a sucção e também aqueles relacionados ao balanço energético. Concentrações mais elevadas de mRNA de MCH têm sido encontrados durante a lactação na área preóptica medial (MPOA) e na parte anterior do núcleo paraventricular do hipotálamo, especialmente em torno do 19º dia de lactação, quando este hormônio revela o seu pico mais alto de expressão do mRNA. O significado fisiológico desse fenômeno não é muito bem compreendido. Neste sentido, o objetivo do presente estudo foi contribuir para a investigação dos fatores que influenciam os sistemas endócrinos e sensoriais na expressão da MCH e a sua relação com alterações neuroendócrinas e comportamentais que envolvem o final da lactação, o desmame e a perpetuação do ciclo reprodutivo. Ratas Wistar (n = 56), foram divididas em subgrupos de quatro animais, as quais foram sacrificadas do 15º ao 21º dia de lactação, com (CS) ou sem (SS) sucção. O MCH e a proteína Fos foram avaliados na área hipotalâmica lateral (LHA), MPOA e área incertohipotalâmica (IHy). A MPOA mostrou uma relação inversa existente entre Fos e MCH. Além disso, observou-se um aumento da proteína Fos no grupo CS, o qual foi menos intensa durante o 18º dia de lactação quando comparado com o 15º dia. Além disso, duplas marcações para MCH e Fos não foram encontradas. Nossos resultados sugerem que a sucção é capaz de influenciar o MCH ao redor do 19º dia de lactação na LHA. Portanto, as áreas que foram encontradas com marcações para Fos podem ser capazes de se comunicarem com as regiões que possuem neurônios produtores de MCH, ou os mecanismos de ativação da expressão de MCH não são repassados via Fos. Sendo assim, parece existir uma relação indireta entre as áreas de ativação neuronal e MCH durante a sucção. / Melanin-Concentrating Hormone (MCH) has been largely implicated in the control of food intake, body weight and energy homeostasis. Moreover, lactation is an important physiological model to study hypothalamic integration to peripheral sensory signals, such as suckling stimulus and also those related to energy balance. Higher concentrations of MCH mRNA have been found during lactation in the medial preoptic area (MPOA) and in the anterior part of the paraventricular nucleus of hypothalamus, especially around the 19th day of lactation when this hormone reveals its highest peak of mRNA expression, and decrease after weaning. The physiological significance of this phenomenon is unclear. In this sense, the aim of the present study was to contribute to the investigation of sensory and endocrine factors influencing in the expression of MCH and its relationship to neuroendocrine and behavioural changes involving the end of lactation, weaning and perpetuating reproductive cycle. Wistar female rats (n= 56), divided in subgroups of four animals, were sacrificed every day from 15th to 21st day of lactation, with (CS) or without (SS) suckling stimulus. MCH and Fos immunoreactivity (MCH/Fos) was evaluated in the lateral hypothalamic area (LHA), MPOA and incerto-hypothalamic area (IHy). The MPOA showed an inverse relationship between Fos and MCH. Also, we observed an increase in the Fos of the group CS, which was less intense on 18th day when compared to 15th day, while MCH was increased. Besides, no colocalization between MCH and Fos was found. Our results suggest that suckling stimulus is able to influence the MCH around the 19th day of lactation in LHA. Therefore, the areas were we found Fos might have stimulated MCH-producing neurons. Hence, an indirect relationship between the areas of neuronal activation and MCH during suckling stimulus seems likely.

O Hormônio Concentrador de Melanina (MCH) está associado ao controle da ingestão de alimentos, peso corporal e homeostase da energia. Além disso, a lactação é um modelo fisiológico importante para estudar a integração do hipotálamo com os sinais sensoriais periféricos, como a sucção e também aqueles relacionados ao balanço energético. Concentrações mais elevadas de mRNA de MCH têm sido encontrados durante a lactação na área preóptica medial (MPOA) e na parte anterior do núcleo paraventricular do hipotálamo, especialmente em torno do 19º dia de lactação, quando este hormônio revela o seu pico mais alto de expressão do mRNA. O significado fisiológico desse fenômeno não é muito bem compreendido. Neste sentido, o objetivo do presente estudo foi contribuir para a investigação dos fatores que influenciam os sistemas endócrinos e sensoriais na expressão da MCH e a sua relação com alterações neuroendócrinas e comportamentais que envolvem o final da lactação, o desmame e a perpetuação do ciclo reprodutivo. Ratas Wistar (n = 56), foram divididas em subgrupos de quatro animais, as quais foram sacrificadas do 15º ao 21º dia de lactação, com (CS) ou sem (SS) sucção. O MCH e a proteína Fos foram avaliados na área hipotalâmica lateral (LHA), MPOA e área incertohipotalâmica (IHy). A MPOA mostrou uma relação inversa existente entre Fos e MCH. Além disso, observou-se um aumento da proteína Fos no grupo CS, o qual foi menos intensa durante o 18º dia de lactação quando comparado com o 15º dia. Além disso, duplas marcações para MCH e Fos não foram encontradas. Nossos resultados sugerem que a sucção é capaz de influenciar o MCH ao redor do 19º dia de lactação na LHA. Portanto, as áreas que foram encontradas com marcações para Fos podem ser capazes de se comunicarem com as regiões que possuem neurônios produtores de MCH, ou os mecanismos de ativação da expressão de MCH não são repassados via Fos. Sendo assim, parece existir uma relação indireta entre as áreas de ativação neuronal e MCH durante a sucção. / Melanin-Concentrating Hormone (MCH) has been largely implicated in the control of food intake, body weight and energy homeostasis. Moreover, lactation is an important physiological model to study hypothalamic integration to peripheral sensory signals, such as suckling stimulus and also those related to energy balance. Higher concentrations of MCH mRNA have been found during lactation in the medial preoptic area (MPOA) and in the anterior part of the paraventricular nucleus of hypothalamus, especially around the 19th day of lactation when this hormone reveals its highest peak of mRNA expression, and decrease after weaning. The physiological significance of this phenomenon is unclear. In this sense, the aim of the present study was to contribute to the investigation of sensory and endocrine factors influencing in the expression of MCH and its relationship to neuroendocrine and behavioural changes involving the end of lactation, weaning and perpetuating reproductive cycle. Wistar female rats (n= 56), divided in subgroups of four animals, were sacrificed every day from 15th to 21st day of lactation, with (CS) or without (SS) suckling stimulus. MCH and Fos immunoreactivity (MCH/Fos) was evaluated in the lateral hypothalamic area (LHA), MPOA and incerto-hypothalamic area (IHy). The MPOA showed an inverse relationship between Fos and MCH. Also, we observed an increase in the Fos of the group CS, which was less intense on 18th day when compared to 15th day, while MCH was increased. Besides, no colocalization between MCH and Fos was found. Our results suggest that suckling stimulus is able to influence the MCH around the 19th day of lactation in LHA. Therefore, the areas were we found Fos might have stimulated MCH-producing neurons. Hence, an indirect relationship between the areas of neuronal activation and MCH during suckling stimulus seems likely.

Thesis advisor: Michael Numan / This paper will review research from our laboratory dealing with the neural basis of maternal behavior in rats. Specifically, my work investigates hypothalamic interaction with the mesolimbic dopamine system and the regulation of maternal responsiveness. Recent evidence has shown that increased dopamine activity in the nucleus accumbens, a major terminus of the mesolimbic dopamine pathway, results in a facilitation of maternal behavior in female rats who have been partially primed by hormones. However, the way in which dopamine and hormones act on these neural circuits is unclear. We hypothesize that one of these hormones, estradiol, acts on the MPOA and mesolimbic dopamine system through similar intracellular mechanisms as dopamine. My research goals are twofold: (1) to discern which G-protein coupled pathway dopamine utilizes to act in the nucleus accumbens and (2) to investigate whether estradiol is having rapid effects at the cell membrane and whether these effects are mediated by G-protein coupled receptors. / Thesis (BA) — Boston College, 2008. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Psychology. / Discipline: College Honors Program.

Maternal behavior is the complex array of caregiving behaviors females display towards offspring. In rats, the transition to motherhood depends on the action of various hormones, especially estradiol near parturition, which primes the maternal circuitry to respond to pups upon first encounter at parturition with appropriate maternal behavior. Although virgin rats avoid pups, new mothers are highly motivated to interact with pups, and their maternal behavior depends on the functional interaction between the medial preoptic area (mPOA) and the ventral tegmental area (VTA). However, a precise mapping of the VTA-projecting mPOA neurons remains to be elucidated. To determine whether pup-responsive neurons in the mPOA project to the VTA, we injected the retrograde tracer Fluorogold (FG) into the VTA of new mother and virgin female rats. Six days later, females were exposed to 3 pups for 5 minutes, and their brains processed to visualize FG and c-Fos immunostaining. In addition, we further characterized the molecular phenotype of these neurons by performing immunohistochemistry against estrogen receptor alpha (Esr1). As expected, the behavior of postpartum and virgin females toward pups was different. Mothers readily approached pups and displayed maternal behavior, whereas virgins avoided interaction with pups. Despite these disparate responses to pups, no differences were found in the number and distribution of mPOAc-Fos→VTA neurons. In addition, in both postpartum and virgin females, a significant proportion of these pup-responsive mPOA→VTA projecting neurons also express Esr1. Further functional interrogation of these c-Fos+/Esr1+ mPOA→VTA neurons in virgins and mothers might elucidate distinct circuit dynamics potentially underlying their behavioral differences towards pups.