Effect of exercise duration on toluene-induced locomotor sensitization in mice: a focus on the Renin Angiotensin System.

IF 3.5 3区医学 Q2 NEUROSCIENCES

Psychopharmacology Pub Date : 2024-10-01 Epub Date: 2024-06-05 DOI:10.1007/s00213-024-06626-5

Itzell A Gallardo-Ortíz, Alain Oros-González, Gabriela Rodríguez-Manzo, René Garduño-Gutiérrez, Andrés Aragón-Martínez, Nayeli Páez-Martínez

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引用次数: 0

Abstract

Rationale: Exercise attenuates addictive behavior; however, little is known about the contribution of exercise duration to this positive effect. The Renin Angiotensin System (RAS) has been implicated both in addictive responses and in the beneficial effects of exercise; though, its role in the advantageous effects of exercise on toluene-induced addictive responses has not been explored.

Objectives: To evaluate the impact of different exercise regimens in mitigating the expression of toluene-induced locomotor sensitization and to analyze changes in RAS elements' expression at the mesocorticolimbic system after repeated toluene exposure and following voluntary wheel running in toluene-sensitized animals.

Methods: Toluene-induced addictive-like response was evaluated with a locomotor sensitization model in mice. Toluene-sensitized animals had access to running wheels 1, 2, 4 or 24 h/day for 4 weeks; thereafter, locomotor sensitization expression was evaluated after a toluene challenge. RAS elements (ACE and ACE2 enzymes; AT1, AT2 and Mas receptors) expression was determined by Western blot in the VTA, NAc and PFCx of toluene-sensitized mice with and without exercise.

Results: Individual differences in toluene-induced locomotor sensitization development were observed. Access to wheel running 1 and 2 h/day reduced but 4 and 24 h/day completely blocked locomotor sensitization expression. Repeated toluene exposure changed RAS elements' expression in the VTA, NAc and PFCx, while exercise mainly modified ACE and AT1 in air-exposed and toluene-sensitized mice.

Conclusions: Inhalant-exposed animals show different sensitization phenotypes. Exercise duration determined its efficacy to attenuate the addictive-like response. Toluene exposure and exercise each modified RAS, the latter also modifying toluene-induced changes.

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运动持续时间对甲苯诱导的小鼠运动敏感性的影响：聚焦肾素血管紧张素系统。

理由：运动可减轻成瘾行为；然而，人们对运动持续时间对这种积极影响的贡献知之甚少。肾素血管紧张素系统（RAS）与成瘾反应和运动的有益作用都有关联；但是，它在运动对甲苯诱发的成瘾反应的有利影响中所起的作用尚未得到探讨：目的：评估不同运动方案对减轻甲苯诱导的运动敏感性表达的影响，并分析甲苯致敏动物反复暴露于甲苯后和自愿轮跑后皮质中层imbic系统中RAS元素表达的变化：方法：采用小鼠运动致敏模型评估甲苯诱导的成瘾样反应。甲苯致敏动物每天1、2、4或24小时接触跑步轮，持续4周；之后，在甲苯挑战后对运动敏感性表达进行评估。用 Western 印迹法测定了运动和不运动的甲苯致敏小鼠的 VTA、NAc 和 PFCx 中 RAS 元素（ACE 和 ACE2 酶；AT1、AT2 和 Mas 受体）的表达：结果：观察到甲苯诱导的运动敏感性发展存在个体差异。每天 1 小时和 2 小时的车轮跑步减少了运动敏感的表达，但每天 4 小时和 24 小时的车轮跑步完全阻止了运动敏感的表达。重复暴露甲苯改变了VTA、NAc和PFCx中RAS元素的表达，而运动主要改变了空气暴露小鼠和甲苯致敏小鼠的ACE和AT1：结论：暴露于吸入剂的动物表现出不同的致敏表型。结论：暴露于吸入剂的动物表现出不同的致敏表型，运动时间的长短决定了其减弱成瘾样反应的效果。甲苯暴露和运动各自改变了RAS，后者还改变了甲苯诱导的变化。

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来源期刊

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.