Cuitavi Javier, Riera-Calabuig Ana, Campos-Jurado Yolanda, Lorente Jesús D, de Jorge María, Polache Ana, Hipólito Lucía
University Institute of Biotechnology and Biomedicine (BIOTECMED), University of Valencia, C/ Dr. Moliner, 50. 46100, Burjassot, Spain; Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Avda. Vicent Andrés Estellés s/n. 46100 Burjassot, Spain.
Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Avda. Vicent Andrés Estellés s/n. 46100 Burjassot, Spain.
Neurochem Int. 2025 Jun;186:105974. doi: 10.1016/j.neuint.2025.105974. Epub 2025 Apr 1.
Alcohol use disorders (AUDs) are influenced by factors that initiate, maintain, and/or induce relapse. Chronic pain is both a risk factor for and consequence of AUD, sharing neurological pathways that affect the mesolimbic dopaminergic system. This study examines how inflammatory pain impacts long-term alcohol intake and mesolimbic dopamine transmission in alcohol-naïve rats. Inflammatory pain was induced in eight-week-old Sprague Dawley rats using complete Freund adjuvant (CFA), while controls received saline. Two protocols were followed: one group had continuous access to 20 % ethanol for one month (n = 10/sex), and the second group for three months (n = 8/sex) in a two-bottle choice paradigm. Mechanical nociception was assessed weekly using the Von Frey test. Dopamine levels in the nucleus accumbens core were measured through microdialysis during the final 1.5 months of ethanol exposure in the second cohort. Due to experimental limitations animals underwent microdialysis at different time points after alcohol was firstly introduced, this was done in a balanced manner by alternating sex and group. After a month of alcohol exposure, rats showed no differences in alcohol consumption. However, from the second month until the end, rats exhibited a non-sex-dependent decrease in alcohol intake, significantly lower in CFA-animals. This reduction was accompanied by a blunted ethanol-evoked dopamine release in the nucleus accumbens. Moreover, low mechanical nociception was maintained until the end of the experiment in CFA-animal. These findings provide insights into the effect of pain on alcohol-elicited neurochemical responses and drinking behaviour, showing how pain alters dopamine response to alcohol, affecting drinking patterns and prolonging nociception from CFA.
酒精使用障碍（AUDs）受引发、维持和/或诱发复发的因素影响。慢性疼痛既是AUD的危险因素，也是其后果，二者共享影响中脑边缘多巴胺能系统的神经通路。本研究探讨炎性疼痛如何影响初饮酒精大鼠的长期酒精摄入量和中脑边缘多巴胺传递。使用完全弗氏佐剂（CFA）在8周龄的Sprague Dawley大鼠中诱发炎性疼痛，而对照组注射生理盐水。遵循两种方案：一组在双瓶选择模式下连续1个月可获取20%乙醇（n = 10/性别），第二组连续3个月（n = 8/性别）。每周使用von Frey试验评估机械性伤害感受。在第二组乙醇暴露的最后1.5个月期间，通过微透析测量伏隔核核心中的多巴胺水平。由于实验限制，动物在首次引入酒精后的不同时间点进行微透析，通过交替性别和组以平衡的方式进行。酒精暴露1个月后，大鼠的酒精消耗量无差异。然而，从第二个月直至实验结束，大鼠的酒精摄入量出现非性别依赖性下降，CFA处理的动物显著更低。这种下降伴随着伏隔核中乙醇诱发的多巴胺释放减弱。此外，CFA处理的动物在实验结束前一直保持低机械性伤害感受。这些发现为疼痛对酒精诱发的神经化学反应和饮酒行为的影响提供了见解，表明疼痛如何改变多巴胺对酒精的反应，影响饮酒模式并延长CFA引起的伤害感受。
