Effect of genetic deletion of nociceptin/orphanin FQ receptors on spatial and associative memory in rats.

IF 3.3 3区 医学 Q2 NEUROSCIENCES
Anna Maria Borruto, Michele Petrella, Sara De Carlo, Nazzareno Cannella, Friedbert Weiss, Roberto Ciccocioppo
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引用次数: 0

Abstract

Rationale: A growing body of evidence suggests that the N/OFQ-NOP receptor system modulates learning and memory in rodents, with NOP receptor agonists impairing memory and antagonists reversing this effect. Moreover, previous studies on transgenic mice showed that genetic deletion of the NOP receptor enhances spatial and aversive memory.

Objectives: To further investigate the role of the NOP receptor system in learning and memory, we used a rat model to assess how genetic deletion of NOP receptors affects spatial and associative memory, comparing it with a wild-type (WT) control group.

Methods: Male Wistar Han and NOP(-/-) rats were tested for spatial memory using the classical Morris Water Maze (MWM) test. A modified MWM was then used to assess cued learning and associative memory. Conditioned place aversion (CPA) further evaluated associative memory. Anxiety-like behavior and motor skills were tested using the Elevated Plus Maze (EPM), Open Field, and Rotarod tests.

Results: NOP(-/-) rats displayed impaired acquisition in the spatial and cued MWM tasks but performed comparably to controls in CPA and spatial MWM retrieval. Notably, NOP(-/-) rats exhibited an anxiogenic-like phenotype in the MWM, EPM, and OF tests, without showing any motor impairment.

Conclusions: Deletion of NOP receptors impairs spatial and associative memory acquisition in the MWM, but this is likely not due to a direct cognitive deficit. Instead, our data suggest that these impairments depend on the anxiogenic-like phenotype observed in NOP(-/-) rats. These findings highlight the complex interplay between anxiety and memory processes in the context of NOP receptor signaling.

痛觉肽/孤啡肽FQ受体基因缺失对大鼠空间记忆和联想记忆的影响。
理由:越来越多的证据表明,N/OFQ-NOP受体系统调节啮齿动物的学习和记忆,NOP受体激动剂损害记忆,拮抗剂逆转这种作用。此外,先前对转基因小鼠的研究表明,NOP受体的基因缺失增强了空间记忆和厌恶记忆。目的:为了进一步研究NOP受体系统在学习和记忆中的作用,我们使用大鼠模型来评估NOP受体基因缺失如何影响空间和联想记忆,并将其与野生型(WT)对照组进行比较。方法:采用Morris水迷宫(MWM)测试雄性Wistar Han和NOP(-/-)大鼠的空间记忆能力。然后使用改进的MWM来评估线索学习和联想记忆。条件位置厌恶(CPA)进一步评价联想记忆。焦虑样行为和运动技能测试采用高架加迷宫(EPM),开放领域,和Rotarod测试。结果:NOP(-/-)大鼠在空间和线索MWM任务中表现出习得障碍,但在CPA和空间MWM检索中表现与对照组相当。值得注意的是,NOP(-/-)大鼠在MWM、EPM和OF测试中表现出焦虑样表型,没有表现出任何运动损伤。结论:NOP受体的缺失损害了MWM的空间和联想记忆获取,但这可能不是由于直接的认知缺陷。相反,我们的数据表明,这些损伤取决于NOP(-/-)大鼠观察到的焦虑样表型。这些发现强调了在NOP受体信号的背景下,焦虑和记忆过程之间复杂的相互作用。
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来源期刊
Psychopharmacology
Psychopharmacology 医学-精神病学
CiteScore
7.10
自引率
5.90%
发文量
257
审稿时长
2-4 weeks
期刊介绍: Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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