Opioid-Dopamine Interactions During Lactation

哺乳期间阿片类药物-多巴胺的相互作用

• 批准号: 7442309
• 负责人: LYDIA A ARBOGAST
• 金额: $ 24.82万
• 依托单位: SOUTHERN ILLINOIS UNIVERSITY CARBONDALE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7442309
• 关键词: Accounting; Anabolism; Anterior Pituitary Hormones; Behavioral; Brain; Brain Stem; Complex; Development; Dopamine; Down-Regulation; Elevation; Endocrine; Enzymes; Event; Gene Proteins; Genes; Genetic Transcription; Histocytochemistry; Hormonal; Human; Human Milk; Hypothalamic structure; In Situ Hybridization; Label; Lactation; Mammary gland; Maternal Behavior; Messenger RNA; Milk; Milk Proteins; Molecular; Neural Pathways; Neuraxis; Neurons; Newborn Infant; Opioid; Opioid Peptide; Opioid Receptor; Pathway interactions; Phosphorylation; Play; Process; Production; Prolactin; Protein Dephosphorylation; Proteins; Rate; Receptor Gene; Regulation; Reproductive Process; Role; Signal Transduction; Spinal Cord; Stimulus; Structure of nucleus infundibularis hypothalami; System; Techniques; Translating; Tyrosine 3-Monooxygenase; Western Blotting; cell growth regulation; dopaminergic neuron; endogenous opioids; immunocytochemistry; protein expression; receptor; receptor expression; response

DESCRIPTION (provided by applicant): Lactation is a reproductive process, which is unique to mammalian species and essential for their survival. Although not critical for human survival, breast milk is considered the optimal nourishment for newborns. Prolactin (PRL) is an anterior pituitary hormone which influences many aspects of lactation including maternal behavior, mammary gland development/ differentiation and the production of milk proteins. Elevated PRL levels are essential for adequate lactation. The initial signal for increased PRL secretion is the suckling of the newborn. The signal is transmitted by a specific neural pathway through the spinal cord and brainstem to the hypothalamus where it acts on neurons to increase PRL release and maintain competent lactation. Tuberoinfundibular dopaminergic (TIDA) neurons in the hypothalamus provide the primary inhibitory influence on PRL release. TIDA neuronal activity is suppressed during lactation, contributing to the elevated levels of PRL. The endogenous opioid peptides are an important component in the neuronal network to translate the suckling stimulus into increased PRL secretion. These opioid peptides contribute to the suppression of TIDA neuronal activity during lactation. However, we do not understand the cellular/molecular processes occurring in the dopaminergic neurons in response to the suckling stimulus and how opioid peptides interact with the dopaminergic neurons to influence these processes. The first specific aim will assess the cellular regulation of tyrosine hydroxylase in TIDA neurons by evaluating the phosphorylation state of tyrosine hydroxylase protein and transcriptional rate for tyrosine hydroxylase gene in response to the suckling stimulus. The second specific aim will evaluate the co-localization of particular opioid receptor subtypes within the TIDA neurons and opioid receptor expression in response to the suckling stimulus. The third specific aim will investigate opioid receptor subtype(s) involved in the control of PRL secretion and TIDA neuronal activity by using selective opioid receptor antagonists. Overall these studies will contribute to our understanding of the complex neuronal pathways involved in maintaining lactation.

描述（由申请人提供）：哺乳是一种生殖过程，是哺乳动物物种所独有的，对其生存至关重要。 尽管母乳对人类生存并不重要，但它被认为是新生儿的最佳营养。 催乳素 (PRL) 是一种垂体前叶激素，影响哺乳的许多方面，包括母亲行为、乳腺发育/分化和乳蛋白的产生。 升高的 PRL 水平对于充足的泌乳至关重要。 PRL 分泌增加的最初信号是新生儿的哺乳。 该信号通过特定的神经通路通过脊髓和脑干传输到下丘脑，在下丘脑作用于神经元以增加 PRL 释放并维持充足的泌乳。 下丘脑中的结节漏斗多巴胺能 (TIDA) 神经元对 PRL 释放具有主要的抑制作用。 TIDA 神经元活动在哺乳期间受到抑制，导致 PRL 水平升高。 内源性阿片肽是神经网络中的重要组成部分，可将哺乳刺激转化为催乳素分泌增加。 这些阿片肽有助于抑制哺乳期间的 TIDA 神经元活动。 然而，我们不了解多巴胺能神经元响应哺乳刺激而发生的细胞/分子过程，以及阿片肽如何与多巴胺能神经元相互作用以影响这些过程。 第一个具体目标是通过评估酪氨酸羟化酶蛋白的磷酸化状态和酪氨酸羟化酶基因响应哺乳刺激的转录率来评估 TIDA 神经元中酪氨酸羟化酶的细胞调节。 第二个具体目标将评估 TIDA 神经元内特定阿片受体亚型的共定位以及响应哺乳刺激的阿片受体表达。 第三个具体目标是通过使用选择性阿片受体拮抗剂来研究参与控制 PRL 分泌和 TIDA 神经元活性的阿片受体亚型。 总的来说，这些研究将有助于我们理解维持泌乳所涉及的复杂神经元通路。