{"title":"Effects of 5-HT1A Receptor Antagonist and 5-HT2A Receptor Agonist on Morphine Withdrawal","authors":"Mahdi Ramezani, Siamak Shahidi, Simin Afshar, Parisa Habibi, Nasrin Hashemi-Firouzi","doi":"10.1134/s1819712424020120","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Chronic administration of morphine causes physical dependence, possibly through serotonin 5‑HT<sub>1A</sub> receptor (5-HT<sub>1A</sub>R) and 5-HT<sub>2A</sub> receptor (5-HT<sub>1A</sub>R). The aim of this study was to evaluate the effect of 5-HT<sub>1A</sub>R antagonist, NAD 299 hydrochloride (NAD 299), and 5-HT<sub>2A</sub> R agonist (TCB-2) on the withdrawal syndrome in morphine-dependent mice. Adult male mice were randomly divided into five groups. Three groups of mice were treated with NAD-299 (0.3 mg/kg, i.p.) and TCB-2 (0.3 mg/kg, i.p.) 15 min before naloxone injection (3 mg/kg, s.c.) to investigate the effect of the 5-HT<sub>1A</sub>R antagonist and 5-HT<sub>2A</sub>R agonist on morphine withdrawal syndrome. Morphine was administered subcutaneously with increasing daily doses at 12-h intervals for five days to induce dependence. The withdrawal symptoms, including jumping, abdomen writhing, body weight loss, and head shakes, were recorded for 30 min. Cortisol and total antioxidant levels were assessed 2 h after the morphine withdrawal test. There was a reduction in total withdrawal score and an increase in head shakes and total antioxidant capacity in the NAD-299 + morphine group compared to the morphine group. The TCB-2 + morphine group exhibited an increase in jumping and a decrease in writhing, head shakes, and withdrawal score compared to the morphine group. The NAD-299 + TCB-2 + morphine group showed a decrease in the number of jumping and total withdrawal score, and an increase in the head shakes and cortisol levels compared to the morphine group. The combined treatment with NAD-299 and TCB-2 modulates the morphine withdrawal syndrome and increases cortisol levels.</p>","PeriodicalId":19119,"journal":{"name":"Neurochemical Journal","volume":"81 1","pages":""},"PeriodicalIF":0.5000,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurochemical Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1134/s1819712424020120","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Chronic administration of morphine causes physical dependence, possibly through serotonin 5‑HT1A receptor (5-HT1AR) and 5-HT2A receptor (5-HT1AR). The aim of this study was to evaluate the effect of 5-HT1AR antagonist, NAD 299 hydrochloride (NAD 299), and 5-HT2A R agonist (TCB-2) on the withdrawal syndrome in morphine-dependent mice. Adult male mice were randomly divided into five groups. Three groups of mice were treated with NAD-299 (0.3 mg/kg, i.p.) and TCB-2 (0.3 mg/kg, i.p.) 15 min before naloxone injection (3 mg/kg, s.c.) to investigate the effect of the 5-HT1AR antagonist and 5-HT2AR agonist on morphine withdrawal syndrome. Morphine was administered subcutaneously with increasing daily doses at 12-h intervals for five days to induce dependence. The withdrawal symptoms, including jumping, abdomen writhing, body weight loss, and head shakes, were recorded for 30 min. Cortisol and total antioxidant levels were assessed 2 h after the morphine withdrawal test. There was a reduction in total withdrawal score and an increase in head shakes and total antioxidant capacity in the NAD-299 + morphine group compared to the morphine group. The TCB-2 + morphine group exhibited an increase in jumping and a decrease in writhing, head shakes, and withdrawal score compared to the morphine group. The NAD-299 + TCB-2 + morphine group showed a decrease in the number of jumping and total withdrawal score, and an increase in the head shakes and cortisol levels compared to the morphine group. The combined treatment with NAD-299 and TCB-2 modulates the morphine withdrawal syndrome and increases cortisol levels.
期刊介绍：
Neurochemical Journal (Neirokhimiya) provides a source for the communication of the latest findings in all areas of contemporary neurochemistry and other fields of relevance (including molecular biology, biochemistry, physiology, neuroimmunology, pharmacology) in an afford to expand our understanding of the functions of the nervous system. The journal presents papers on functional neurochemistry, nervous system receptors, neurotransmitters, myelin, chromaffin granules and other components of the nervous system, as well as neurophysiological and clinical aspects, behavioral reactions, etc. Relevant topics include structure and function of the nervous system proteins, neuropeptides, nucleic acids, nucleotides, lipids, and other biologically active components.
The journal is devoted to the rapid publication of regular papers containing the results of original research, reviews highlighting major developments in neurochemistry, short communications, new experimental studies that use neurochemical methodology, descriptions of new methods of value for neurochemistry, theoretical material suggesting novel principles and approaches to neurochemical problems, presentations of new hypotheses and significant findings, discussions, chronicles of congresses, meetings, and conferences with short presentations of the most sensational and timely reports, information on the activity of the Russian and International Neurochemical Societies, as well as advertisements of reagents and equipment.
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