雌性大鼠急性奥氮平治疗后下丘脑-阿片受体表达的变化:对摄食行为的影响

IF 2.7 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of chemical neuroanatomy Pub Date : 2023-10-01 DOI:10.1016/j.jchemneu.2023.102324
Maiken Krogsbaek , Nick Yao Larsen , Anne M. Landau , Connie Sanchez , Jens Randel Nyengaard
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引用次数: 0

摘要

近年来,在使用阿片受体拮抗剂作为精神药物的辅助治疗方面取得了进展,以减少与第二代抗精神病药物相关的衰弱性体重增加和代谢不良反应。然而,尚不清楚第二代抗精神病药物是否会改变大脑中阿片受体的表达。本研究研究了雌性大鼠下丘脑中阿片受体表达的早期变化,下丘脑是饥饿和代谢调节的主要控制者,在急性使用奥氮平(一种常用的第二代抗精神病药)后。采用定量空间原位杂交和受体放射自显影技术,检测三种阿片受体的表达水平;分别测定下丘脑室旁核、弓形核、腹内侧核、背内侧核和外侧下丘脑5个区域的kappa、mu和delta mRNA和蛋白水平。奥氮平治疗48 h后,观察到雌性大鼠的临床相关血药浓度、体重增加、摄食量变化及血糖升高。奥氮平治疗还导致弓状核中mu阿片受体的可用性显著增加,弓状核包含饱腹感和饥饿控制神经元。其他区域在mRNA和蛋白水平上均未见阿片受体表达变化。由于技术上的困难,无法分析下丘脑外侧的mRNA水平和δ阿片受体的总体结合。因此,本研究为临床相关的早期血浆水平的奥氮平如何调节下丘脑的阿片系统提供了见解。
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Changes in hypothalamic mu-opioid receptor expression following acute olanzapine treatment in female rats: Implications for feeding behavior

Advances have been made in recent years in using opioid receptor antagonists as an adjunct therapy to psychotropic medication to reduce debilitating weight gain and metabolic adverse effects associated with in particular second generation antipsychotics. However, it is unknown whether second generation antipsychotics produce a change in opioid receptor expression in the brain. The present study investigated early changes in opioid receptor expression in the female rat hypothalamus, a master controller of hunger and metabolic regulation, after acute treatment with olanzapine, a commonly used second generation antipsychotic. Using quantitative spatial in situ hybridization and receptor autoradiography, expression levels of the three opioid receptors; kappa, mu and delta, were determined at mRNA and protein level, respectively, in the five hypothalamic areas: paraventricular nucleus, arcuate nucleus, ventromedial nucleus, dorsomedial nucleus and lateral hypothalamus. After 48 h of olanzapine treatment at clinically relevant plasma concentration weight gain and food intake changes, and increased plasma glucose were observed in female rats. Olanzapine treatment also led to a significant increase in mu opioid receptor availability in the arcuate nucleus, which contains both satiety and hunger controlling neurons. No other areas showed any opioid receptor expressional changes with olanzapine treatment on neither at mRNA nor protein level. Technical difficulties made it impossible to analyze mRNA levels in the lateral hypothalamus and overall binding of delta opioid receptors. Thus, the present study provided insights in to how olanzapine at clinically relevant plasma levels already at an early stage modulated the opioid system in the hypothalamus.

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来源期刊
Journal of chemical neuroanatomy
Journal of chemical neuroanatomy 医学-神经科学
CiteScore
4.50
自引率
3.60%
发文量
87
审稿时长
62 days
期刊介绍: The Journal of Chemical Neuroanatomy publishes scientific reports relating the functional and biochemical aspects of the nervous system with its microanatomical organization. The scope of the journal concentrates on reports which combine microanatomical, biochemical, pharmacological and behavioural approaches. Papers should offer original data correlating the morphology of the nervous system (the brain and spinal cord in particular) with its biochemistry. The Journal of Chemical Neuroanatomy is particularly interested in publishing important studies performed with up-to-date methodology utilizing sensitive chemical microassays, hybridoma technology, immunocytochemistry, in situ hybridization and receptor radioautography, to name a few examples. The Journal of Chemical Neuroanatomy is the natural vehicle for integrated studies utilizing these approaches. The articles will be selected by the editorial board and invited reviewers on the basis of their excellence and potential contribution to this field of neurosciences. Both in vivo and in vitro integrated studies in chemical neuroanatomy are appropriate subjects of interest to the journal. These studies should relate only to vertebrate species with particular emphasis on the mammalian and primate nervous systems.
期刊最新文献
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