scholarly journals Mice with high FGF21 serum levels had a reduced preference for morphine and an attenuated development of acute antinociceptive tolerance and physical dependence

2021 ◽  
pp. 108858
Author(s):  
Louben Dorval ◽  
Brian I. Knapp ◽  
Olufolake A. Majekodunmi ◽  
Sophia Eliseeva ◽  
Jean M. Bidlack
2021 ◽  
Author(s):  
Louben Dorval ◽  
Brian I. Knapp ◽  
Olufolake A. Majekodunmi ◽  
Sophia Eliseeva ◽  
Jean M Bidlack

As a result of the opioid epidemic, there is a desire to identify new targets for treating opioid use disorder. Previous studies showed that fibroblast growth factor 21 (FGF21) decreased alcohol and sweet preference in mice. In this study, FGF21-transgenic (FGF21-Tg) mice, expressing high FGF21 serum levels, and wildtype (WT) C57BL/6J littermates were treated with morphine and saline to determine if differences exist in their physiological and behavioral responses to opioids. FGF21-Tg mice displayed reduced preference for morphine in the conditioned place preference assay compared to WT littermates. Similarly, FGF21-Tg mice had an attenuation of the magnitude and rate of acute morphine antinociceptive tolerance development, and acute and chronic morphine physical dependence, but exhibited no change in chronic morphine antinociceptive tolerance. The ED50 values for morphine-induced antinociception in the 55-degree C hot plate and the 55-degree C warm-water tail withdrawal assays were similar in both strains of mice. Likewise, FGF21-Tg and WT littermates had comparable responses to morphine-induced respiratory depression. Overall, FGF21-Tg mice had an attenuated preference for morphine, a reduced development of morphine-induced dependence, and a reduction in the development of acute morphine antinociceptive tolerance. FGF21 and its receptor have therapeutic potential for reducing opioid withdrawal symptoms and craving, and augmenting opioid therapeutics for acute pain treatment.


Author(s):  
Т.П. Ветлугина ◽  
Е.В. Матафонова ◽  
Н.А. Бохан ◽  
В.Б. Никитина ◽  
А.И. Мандель ◽  
...  

Цель исследования: изучение динамики показателей иммунитета и уровня кортизола у больных опийной наркоманией в процессе терапии синдрома отмены. Методика. В исследование включено 136 больных опийной наркоманией (инъекции экстракта опия) с сформировавшейся физической зависимостью. Пациенты получали в стационаре стандартную терапию с полной отменой наркотика. Исследование проводилось на следующих этапах: при поступлении в стационар (опийный абстинентный синдром - ОАС); на 5-7-е сут. терапии (переход в постабстинентное состояние - ПАС); на 25-28-е сут. лечения (становление терапевтической ремиссии - СТР). Лабораторные методы включали определение количества лимфоцитов с рецепторами CD3, CD4, CD8, СD16, с рецепторами к дофамину (D-RFC); содержание иммуноглобулинов М, G, А, уровня кортизола и циркулирующих иммунных комплексов (ЦИК) в сыворотке крови. Результаты. Основной иммуноэндокринный паттерн на всех этапах терапии синдрома отмены характеризуется дефицитом субпопуляций Т-лимфоцитов CD3, CD4, СD8; увеличением числа лимфоцитов с рецепторами к дофамину (D-RFC); активацией гуморальных факторов иммунитета (IgM, IgG, ЦИК); высокой концентрацией кортизола. На этапе ОАС и ПАС эти изменения были наиболее выражены; на 25-28-е сут. лечения отмечена позитивная динамика Т-лимфоцитов СD3 и цитотоксических Т-лимфоцитов (СD8); хелперы/индукторы CD4 оставались устойчиво сниженными; D-RFC лимфоциты, параметры гуморального иммунитета и концентрация кортизола - повышенными. Длительный срок наркотизации при употреблении высоких доз наркотика связан с большей выраженностью нарушений. Заключение. Установленная дизрегуляция параметров иммуноэндокринной системы у больных опийной наркоманией на всех этапах терапии синдрома отмены в наблюдаемые сроки (25-28 сут.) свидетельствует о неустойчивости достигнутой терапевтической ремиссии и необходимости проведения дальнейших реабилитационных мероприятий. The purpose: investigate changes in immunity parameters and cortisol level in subjects with opiate addiction during the treatment of opiate withdrawal syndrome. Methods. The study enrolled 136 subjects with opiate addiction with physical dependence receiving injections of opium extract. Patients received conventional therapy with complete opiate withdrawal. The study was performed at the following stages: at admission to the hospital (acute withdrawal syndrome (AWS); on days 5-7 of therapy (transition into post-withdrawal state - PWS); on days 25-28 of therapy (formation of therapeutic remission - FTR). Laboratory methods included determination count of lymphocytes with receptors CD3, CD4, CD8, СD16, with receptors to dopamine (D-RFC); the serum levels of IgМ, IgG, IgА, cortisol, circulating immune complexes (CIC). Results. The principal immunoendocrine pattern for all stages of withdrawal syndrome therapy is characterized in comparison to the reference normal values quantitative deficit of CD3, CD4, СD8 Т-lymphocyte subpopulations, increased count of lymphocytes with receptors to dopamine, activation of humoral immunity factors (IgM, IgG, CIC), high cortisol level. At AWS and PAS stages such changes are most pronounced; on days 25-28 of therapy positive changes in cytotoxic Т-lymphocytes (СD8) and Т-lymphocytes СD3 was revealed. CD4 count remained steadily reduced, count of lymphocytes with receptors to dopamine and cortisol level were elevated. Clinical and immunological analysis demonstrated that consumption of high opiate doses, long-term narcotization are associated with higher intensity of disorders detected. Conclusion. Dysregulation of immunoendocrine parameters was revealed in subjects with opiate addiction at all stages of withdrawal syndrome therapy within the term observed evidencing instability of therapeutic remission achieved and necessity in further rehabilitation events.


2021 ◽  
pp. 174245
Author(s):  
Renata Wolińska ◽  
Patrycja Kleczkowska ◽  
Anna de Cordé-Skurska ◽  
Piotr Poznański ◽  
Mariusz Sacharczuk ◽  
...  

2010 ◽  
Vol 21 (5-6) ◽  
pp. 523-529 ◽  
Author(s):  
Chin-Chen Chu ◽  
Ja-Ping Shieh ◽  
Hao-Ai Shui ◽  
Jen-Yin Chen ◽  
Chung-Hsi Hsing ◽  
...  

2011 ◽  
Vol 338 (1) ◽  
pp. 164-172 ◽  
Author(s):  
Cheng Yang ◽  
Yan Chen ◽  
Lei Tang ◽  
Zaijie Jim Wang

2015 ◽  
Vol 137 ◽  
pp. 38-43 ◽  
Author(s):  
Mohammad Taghi Mansouri ◽  
Mohammad Javad Khodayar ◽  
Amirhossein Tabatabaee ◽  
Behnam Ghorbanzadeh ◽  
Bahareh Naghizadeh

2018 ◽  
Vol 835 ◽  
pp. 52-60 ◽  
Author(s):  
Mahsa Hassanipour ◽  
Nazanin Rajai ◽  
Nastaran Rahimi ◽  
Iman Fatemi ◽  
Mitra Jalali ◽  
...  

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 55
Author(s):  
Lucja Kudla ◽  
Ryszard Bugno ◽  
Sabina Podlewska ◽  
Lukasz Szumiec ◽  
Lucja Wiktorowska ◽  
...  

Among different approaches to the search for novel—safer and less addictive—opioid analgesics, biased agonism has received the most attention in recent years. Some μ-opioid receptor agonists with G protein bias, including SR compounds, were proposed to induce diminished side effects. However, in many aspects, behavioral effects of those compounds, as well as the mechanisms underlying differences in their action, remain unexplored. Here, we aimed to evaluate the effects of SR-14968 and SR-17018, highly G protein-biased opioid agonists, on antinociception, motor activity and addiction-like behaviors in C57BL/6J mice. The obtained results showed that the compounds induce strong and dose-dependent antinociception. SR-14968 causes high, and SR-17018 much lower, locomotor activity. Both agonists develop reward-associated behavior and physical dependence. The compounds also cause antinociceptive tolerance, however, developing more slowly when compared to morphine. Interestingly, SR compounds, in particular SR-17018, slow down the development of antinociceptive tolerance to morphine and inhibit some symptoms of morphine withdrawal. Therefore, our results indicate that SR agonists possess rewarding and addictive properties, but can positively modulate some symptoms of morphine dependence. Next, we have compared behavioral effects of SR-compounds and PZM21 and searched for a relationship to the substantial differences in molecular interactions that these compounds form with the µ-opioid receptor.


Sign in / Sign up

Export Citation Format

Share Document