Anna Maria Borruto, Michele Petrella, Sara De Carlo, Nazzareno Cannella, Friedbert Weiss, Roberto Ciccocioppo
{"title":"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。","authors":"Anna Maria Borruto, Michele Petrella, Sara De Carlo, Nazzareno Cannella, Friedbert Weiss, Roberto Ciccocioppo","doi":"10.1007/s00213-025-06842-7","DOIUrl":null,"url":null,"abstract":"<p><strong>Rationale: </strong>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.</p><p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>Male Wistar Han and NOP<sup>(-/-)</sup> 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.</p><p><strong>Results: </strong>NOP<sup>(-/-)</sup> rats displayed impaired acquisition in the spatial and cued MWM tasks but performed comparably to controls in CPA and spatial MWM retrieval. Notably, NOP<sup>(-/-)</sup> rats exhibited an anxiogenic-like phenotype in the MWM, EPM, and OF tests, without showing any motor impairment.</p><p><strong>Conclusions: </strong>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<sup>(-/-)</sup> rats. These findings highlight the complex interplay between anxiety and memory processes in the context of NOP receptor signaling.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effect of genetic deletion of nociceptin/orphanin FQ receptors on spatial and associative memory in rats.\",\"authors\":\"Anna Maria Borruto, Michele Petrella, Sara De Carlo, Nazzareno Cannella, Friedbert Weiss, Roberto Ciccocioppo\",\"doi\":\"10.1007/s00213-025-06842-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Rationale: </strong>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.</p><p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>Male Wistar Han and NOP<sup>(-/-)</sup> 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.</p><p><strong>Results: </strong>NOP<sup>(-/-)</sup> rats displayed impaired acquisition in the spatial and cued MWM tasks but performed comparably to controls in CPA and spatial MWM retrieval. Notably, NOP<sup>(-/-)</sup> rats exhibited an anxiogenic-like phenotype in the MWM, EPM, and OF tests, without showing any motor impairment.</p><p><strong>Conclusions: </strong>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<sup>(-/-)</sup> rats. These findings highlight the complex interplay between anxiety and memory processes in the context of NOP receptor signaling.</p>\",\"PeriodicalId\":20783,\"journal\":{\"name\":\"Psychopharmacology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2025-07-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Psychopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00213-025-06842-7\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00213-025-06842-7","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Effect of genetic deletion of nociceptin/orphanin FQ receptors on spatial and associative memory in rats.
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.
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
