The Influence of the Estrous Cycle on Neuropeptide S Receptor-Mediated Behaviors.

IF 3.1 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Paula Carvalho Costa, Brisa Salinas, Alaina Wojciechowski, Susan K Wood, Scott Runyon, Stewart D Clark
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引用次数: 0

Abstract

The neuropeptide S receptor (NPSR) has been identified as a potential therapeutic target for anxiety and post-traumatic stress disorder. Central administration of neuropeptide S (NPS) in male mice produces anxiolytic-like effects, hyperlocomotion, and memory enhancement. Currently, the literature is limited in the number of studies investigating the effects of NPS in female test subjects despite females facing a higher prevalence of anxiety-related pathology, as well as greater risk for adverse effects while taking psychoactive drugs. Moreover, no previous studies have considered the influence of estrous cycle on the effects of NPS. The present study investigates whether NPS-mediated behavioral phenotypes seen in males translate to females, and whether they are affected by estrous cycle stage. Female C57BL/6NCr mice were intracerebroventricularly cannulated and underwent behavioral paradigms to test locomotion, anxiety, and memory. Estrous cycle stage was determined through examination of vaginal cytology. Our results provide evidence that NPS-mediated behaviors are influenced by the estrous cycle. Administration of NPS decreased anxiety-like behaviors more robustly when the female mice were in high estrogen stages of the estrous cycle. Therefore, the desired anxiolytic-like effects of targeting the NPSR are intact in female mice. However, these effects may to be influenced by the stage of the estrous cycle. The NPSR remains a strong potential drug target for new anxiolytic compounds and based on our initial observations further studies exploring the interaction of estrous cycle and the NPS system are warranted. SIGNIFICANCE STATEMENT: The neuropeptide S (NPS) receptor has been identified as a potential target for treating anxiety, a condition that is most prevalent in females. Therefore, the potential interaction of estrous cycle with the NPS system described in the present study is an important first step in understanding the function of the NPS system in females.

动情周期对神经肽 S 受体介导行为的影响
神经肽 S 受体(NPSR)已被确定为焦虑症和创伤后应激障碍的潜在治疗靶点。对雄性小鼠中枢注射神经肽 S(NPS)可产生抗焦虑样效应、运动过度和记忆增强。目前,尽管女性焦虑相关病症的发病率更高,而且在服用精神活性药物时出现不良反应的风险更大,但有关 NPS 对女性受试者影响的研究数量有限。此外,以前的研究也没有考虑过发情周期对 NPS 作用的影响。本研究调查了 NPS 介导的行为表型在雄性动物身上的表现是否会转化到雌性动物身上,以及它们是否会受到发情周期阶段的影响。对雌性 C57BL/6NCr 小鼠进行脑室内插管,并对其进行行为范式试验,以测试其运动、焦虑和记忆能力。通过检查阴道细胞学确定动情周期阶段。我们的研究结果证明,NPS介导的行为受发情周期的影响。当雌性小鼠处于发情周期的高雌激素阶段时,服用 NPS 能更有效地减少焦虑行为。因此,针对 NPSR 的预期抗焦虑样效应在雌性小鼠中是完整的。不过,这些效应可能会受到发情周期阶段的影响。NPSR仍然是新抗焦虑化合物的一个强大的潜在药物靶点,基于我们的初步观察,有必要进一步研究发情周期与NPS系统之间的相互作用。意义声明 神经肽 S(NPS)受体已被确定为治疗女性焦虑症的潜在靶点。因此,本研究中描述的发情周期与 NPS 系统之间的潜在相互作用是了解女性 NPS 系统功能的重要的第一步。
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来源期刊
CiteScore
6.90
自引率
0.00%
发文量
115
审稿时长
1 months
期刊介绍: A leading research journal in the field of pharmacology published since 1909, JPET provides broad coverage of all aspects of the interactions of chemicals with biological systems, including autonomic, behavioral, cardiovascular, cellular, clinical, developmental, gastrointestinal, immuno-, neuro-, pulmonary, and renal pharmacology, as well as analgesics, drug abuse, metabolism and disposition, chemotherapy, and toxicology.
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