2,5-二甲氧基-4-碘苯丙胺和阿坦色林诱导大鼠大脑中多巴胺和血清素代谢途径发生特定区域性转变

IF 3.3 3区 心理学 Q1 BEHAVIORAL SCIENCES Pharmacology Biochemistry and Behavior Pub Date : 2024-07-11 DOI:10.1016/j.pbb.2024.173823
Susanne Nikolaus , Benedetta Fazari , Owen Y. Chao , Filipe Rodrigues Almeida , Laila Abdel-Hafiz , Markus Beu , Jan Henke , Christina Antke , Hubertus Hautzel , Eduards Mamlins , Hans-Wilhelm Müller , Joseph P. Huston , Charlotte von Gall , Frederik L. Giesel
{"title":"2,5-二甲氧基-4-碘苯丙胺和阿坦色林诱导大鼠大脑中多巴胺和血清素代谢途径发生特定区域性转变","authors":"Susanne Nikolaus ,&nbsp;Benedetta Fazari ,&nbsp;Owen Y. Chao ,&nbsp;Filipe Rodrigues Almeida ,&nbsp;Laila Abdel-Hafiz ,&nbsp;Markus Beu ,&nbsp;Jan Henke ,&nbsp;Christina Antke ,&nbsp;Hubertus Hautzel ,&nbsp;Eduards Mamlins ,&nbsp;Hans-Wilhelm Müller ,&nbsp;Joseph P. Huston ,&nbsp;Charlotte von Gall ,&nbsp;Frederik L. Giesel","doi":"10.1016/j.pbb.2024.173823","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><p>For understanding the neurochemical mechanism of neuropsychiatric conditions associated with cognitive deficits it is of major relevance to elucidate the influence of serotonin (5-HT) agonists and antagonists on memory function as well dopamine (DA) and 5-HT release and metabolism. In the present study, we assessed the effects of the 5-HT<sub>2A</sub> receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) and the 5-HT<sub>2A</sub> receptor altanserin (ALT) on object and place recognition memory and cerebral neurotransmitters and metabolites in the rat.</p></div><div><h3>Methods</h3><p>Rats underwent a 5-min exploration trial in an open field with two identical objects. After systemic injection of a single dose of either DOI (0.1 mg/kg), ALT (1 mg/kg) or the respectice vehicle (0.9 % NaCl, 50 % DMSO), rats underwent a 5-min test trial with one of the objects replaced by a novel one and the other object transferred to a novel place. Upon the assessment of object exploration and motor/exploratory behaviors, rats were sacrificed. DA, 5-HT and metabolite levels were analyzed in cingulate (CING), caudateputamen (CP), nucleus accumbens (NAC), thalamus (THAL), dorsal (dHIPP) and ventral hippocampus (vHIPP), brainstem and cerebellum with high performance liquid chromatography.</p></div><div><h3>Results</h3><p>DOI decreased rearing but increased head-shoulder motility relative to vehicle. Memory for object and place after both DOI and ALT was not different from vehicle. Network analyses indicated that DOI inhibited DA metabolization in CING, CP, NAC, and THAL, but facilitated it in dHIPP. Likewise, DOI inhibited 5-HT metabolization in CING, NAC, and THAL. ALT facilitated DA metabolization in the CING, NAC, dHIPP, vHIPP, and CER, but inhibited it in the THAL. Additionally, ALT facilitated 5-HT metabolization in NAC and dHIPP.</p></div><div><h3>Conclusions</h3><p>DOI and ALT differentially altered the quantitative relations between the neurotransmitter/metabolite levels in the individual brain regions, by inducing region-specific shifts in the metabolization pathways. Findings are relevant for understanding the neurochemistry underlying DAergic and/or 5-HTergic dysfunction in neurological and psychiatric conditions.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"242 ","pages":"Article 173823"},"PeriodicalIF":3.3000,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0091305724001175/pdfft?md5=391c635a379ee00471e0425513cdda90&pid=1-s2.0-S0091305724001175-main.pdf","citationCount":"0","resultStr":"{\"title\":\"2,5-Dimethoxy-4-iodoamphetamine and altanserin induce region-specific shifts in dopamine and serotonin metabolization pathways in the rat brain\",\"authors\":\"Susanne Nikolaus ,&nbsp;Benedetta Fazari ,&nbsp;Owen Y. Chao ,&nbsp;Filipe Rodrigues Almeida ,&nbsp;Laila Abdel-Hafiz ,&nbsp;Markus Beu ,&nbsp;Jan Henke ,&nbsp;Christina Antke ,&nbsp;Hubertus Hautzel ,&nbsp;Eduards Mamlins ,&nbsp;Hans-Wilhelm Müller ,&nbsp;Joseph P. Huston ,&nbsp;Charlotte von Gall ,&nbsp;Frederik L. Giesel\",\"doi\":\"10.1016/j.pbb.2024.173823\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Purpose</h3><p>For understanding the neurochemical mechanism of neuropsychiatric conditions associated with cognitive deficits it is of major relevance to elucidate the influence of serotonin (5-HT) agonists and antagonists on memory function as well dopamine (DA) and 5-HT release and metabolism. In the present study, we assessed the effects of the 5-HT<sub>2A</sub> receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) and the 5-HT<sub>2A</sub> receptor altanserin (ALT) on object and place recognition memory and cerebral neurotransmitters and metabolites in the rat.</p></div><div><h3>Methods</h3><p>Rats underwent a 5-min exploration trial in an open field with two identical objects. After systemic injection of a single dose of either DOI (0.1 mg/kg), ALT (1 mg/kg) or the respectice vehicle (0.9 % NaCl, 50 % DMSO), rats underwent a 5-min test trial with one of the objects replaced by a novel one and the other object transferred to a novel place. Upon the assessment of object exploration and motor/exploratory behaviors, rats were sacrificed. DA, 5-HT and metabolite levels were analyzed in cingulate (CING), caudateputamen (CP), nucleus accumbens (NAC), thalamus (THAL), dorsal (dHIPP) and ventral hippocampus (vHIPP), brainstem and cerebellum with high performance liquid chromatography.</p></div><div><h3>Results</h3><p>DOI decreased rearing but increased head-shoulder motility relative to vehicle. Memory for object and place after both DOI and ALT was not different from vehicle. Network analyses indicated that DOI inhibited DA metabolization in CING, CP, NAC, and THAL, but facilitated it in dHIPP. Likewise, DOI inhibited 5-HT metabolization in CING, NAC, and THAL. ALT facilitated DA metabolization in the CING, NAC, dHIPP, vHIPP, and CER, but inhibited it in the THAL. Additionally, ALT facilitated 5-HT metabolization in NAC and dHIPP.</p></div><div><h3>Conclusions</h3><p>DOI and ALT differentially altered the quantitative relations between the neurotransmitter/metabolite levels in the individual brain regions, by inducing region-specific shifts in the metabolization pathways. Findings are relevant for understanding the neurochemistry underlying DAergic and/or 5-HTergic dysfunction in neurological and psychiatric conditions.</p></div>\",\"PeriodicalId\":19893,\"journal\":{\"name\":\"Pharmacology Biochemistry and Behavior\",\"volume\":\"242 \",\"pages\":\"Article 173823\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-07-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0091305724001175/pdfft?md5=391c635a379ee00471e0425513cdda90&pid=1-s2.0-S0091305724001175-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmacology Biochemistry and Behavior\",\"FirstCategoryId\":\"102\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0091305724001175\",\"RegionNum\":3,\"RegionCategory\":\"心理学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BEHAVIORAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacology Biochemistry and Behavior","FirstCategoryId":"102","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0091305724001175","RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
引用次数: 0

摘要

研究目的为了解与认知缺陷相关的神经精神疾病的神经化学机制,阐明血清素(5-HT)激动剂和拮抗剂对记忆功能以及多巴胺(DA)和 5-HT 释放和代谢的影响具有重要意义。为此,我们评估了 2,5-二甲氧基-4-碘苯丙胺(DOI)和阿坦色林(ALT)对大鼠物体和地点识别记忆以及脑神经递质和代谢物的影响:大鼠在空地上对两个相同的物体进行 5 分钟的探索试验。大鼠在全身注射单剂量 DOI(0.1 毫克/千克)、ALT(1 毫克/千克)或药物载体(0.9 % NaCl,50 % DMSO)后,进行 5 分钟的测试试验,将其中一个物体替换为新物体,另一个物体转移到新地点。在对大鼠的物体探索和运动/探索行为进行评估后,将大鼠处死。用高效液相色谱法分析了扣带回(CING)、尾状核(CP)、伏隔核(NAC)、丘脑(THAL)、海马背侧(dHIPP)和腹侧(vHIPP)、脑干和小脑中的DA、5-HT和代谢物水平:与车辆相比,DOI减少了爬行,但增加了头肩运动。DOI和ALT对物体和地点的记忆与车辆没有差异。网络分析表明,DOI抑制了CING、CP、NAC和THAL中的DA代谢,但促进了dHIPP中的DA代谢。同样,DOI 在 CING、NAC 和 THAL 中抑制 5-HT 代谢。ALT 在 CING、NAC、dHIPP、vHIPP 和 CER 中促进 DA 的代谢,但在 THAL 中抑制 DA 的代谢。此外,ALT 还能促进 5-HT 在 NAC 和 dHIPP 中的代谢:结论:DOI 和 ALT 通过诱导特定区域代谢途径的转变,不同程度地改变了各个脑区神经递质/代谢物水平之间的定量关系。这些发现有助于了解神经和精神疾病中DA能和/或5-HT能功能障碍的神经化学原理。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
2,5-Dimethoxy-4-iodoamphetamine and altanserin induce region-specific shifts in dopamine and serotonin metabolization pathways in the rat brain

Purpose

For understanding the neurochemical mechanism of neuropsychiatric conditions associated with cognitive deficits it is of major relevance to elucidate the influence of serotonin (5-HT) agonists and antagonists on memory function as well dopamine (DA) and 5-HT release and metabolism. In the present study, we assessed the effects of the 5-HT2A receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) and the 5-HT2A receptor altanserin (ALT) on object and place recognition memory and cerebral neurotransmitters and metabolites in the rat.

Methods

Rats underwent a 5-min exploration trial in an open field with two identical objects. After systemic injection of a single dose of either DOI (0.1 mg/kg), ALT (1 mg/kg) or the respectice vehicle (0.9 % NaCl, 50 % DMSO), rats underwent a 5-min test trial with one of the objects replaced by a novel one and the other object transferred to a novel place. Upon the assessment of object exploration and motor/exploratory behaviors, rats were sacrificed. DA, 5-HT and metabolite levels were analyzed in cingulate (CING), caudateputamen (CP), nucleus accumbens (NAC), thalamus (THAL), dorsal (dHIPP) and ventral hippocampus (vHIPP), brainstem and cerebellum with high performance liquid chromatography.

Results

DOI decreased rearing but increased head-shoulder motility relative to vehicle. Memory for object and place after both DOI and ALT was not different from vehicle. Network analyses indicated that DOI inhibited DA metabolization in CING, CP, NAC, and THAL, but facilitated it in dHIPP. Likewise, DOI inhibited 5-HT metabolization in CING, NAC, and THAL. ALT facilitated DA metabolization in the CING, NAC, dHIPP, vHIPP, and CER, but inhibited it in the THAL. Additionally, ALT facilitated 5-HT metabolization in NAC and dHIPP.

Conclusions

DOI and ALT differentially altered the quantitative relations between the neurotransmitter/metabolite levels in the individual brain regions, by inducing region-specific shifts in the metabolization pathways. Findings are relevant for understanding the neurochemistry underlying DAergic and/or 5-HTergic dysfunction in neurological and psychiatric conditions.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
6.40
自引率
2.80%
发文量
122
审稿时长
38 days
期刊介绍: Pharmacology Biochemistry & Behavior publishes original reports in the areas of pharmacology and biochemistry in which the primary emphasis and theoretical context are behavioral. Contributions may involve clinical, preclinical, or basic research. Purely biochemical or toxicology studies will not be published. Papers describing the behavioral effects of novel drugs in models of psychiatric, neurological and cognitive disorders, and central pain must include a positive control unless the paper is on a disease where such a drug is not available yet. Papers focusing on physiological processes (e.g., peripheral pain mechanisms, body temperature regulation, seizure activity) are not accepted as we would like to retain the focus of Pharmacology Biochemistry & Behavior on behavior and its interaction with the biochemistry and neurochemistry of the central nervous system. Papers describing the effects of plant materials are generally not considered, unless the active ingredients are studied, the extraction method is well described, the doses tested are known, and clear and definite experimental evidence on the mechanism of action of the active ingredients is provided.
期刊最新文献
Dusting off old blueprints: Is it time to reconsider metabotropic glutamate receptor 2 for therapeutic drug development? Conditioned place preference with low dose mixtures of α-pyrrolidinopentiophenone (α-PVP) and 3,4-methylenedioxypyrovalerone (MDPV) in male and female Sprague-Dawley rats. Splenic γδ T cells mediate antidepressant and prophylactic actions of arketamine in lipopolysaccharide-induced depression in mice Mescaline-induced behavioral alterations are mediated by 5-HT2A and 5-HT2C receptors in rats. ANXIOLYTICS: Introduction to a special issue celebrating 50 years of Pharmacology, Biochemistry and Behavior
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1