Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Burjassot, Spain; Instituto Universitario de Biotecnología y Biomedicina (BIOTECMED), University of Valencia, Burjassot, Spain.
Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Burjassot, Spain.
Pharmacol Biochem Behav. 2024 Nov;244:173845. doi: 10.1016/j.pbb.2024.173845. Epub 2024 Aug 3.
Alcohol consumption leads to significant neurochemical and neurobiological changes, contributing to the development of alcohol use disorders (AUDs), which exhibit sex- and age-dependent variations according to clinical data. However, preclinical studies often neglect these factors when investigating alcohol consumption patterns. In this study, we present data on male and female rats continuously exposed to a 20 % ethanol solution for one month. The animals were divided into two groups based on their age at the onset of drinking (8 and 12 weeks old). Interestingly, 12-week-old males consumed significantly less alcohol than both 12-week-old females and 8-week-old animals, indicating that alcohol consumption patterns vary with sex and age in our model. Additionally, to advance in the study of the neurobiological alterations induced by ethanol intake in the mesocorticolimbic system (MCLS) that may participate in its reinforcing properties and the maintenance of alcohol drinking behavior, we measured catalase activity-an enzyme involved in alcohol metabolism and related to ethanol reinforcement-in the nucleus accumbens (NAc) of these animals. Furthermore, we measured the levels of mu (MOR), kappa (KOR), delta (DOR), and nociceptin (NOP) opioid receptors in the NAc, as the endogenous opioidergic system plays a pivotal role in regulating the MCLS and alcohol reinforcement. MOR levels were lower in high alcohol-consuming groups (8-week-old males and all females). Both DOR and NOP levels decreased with age, whereas KOR levels remained unchanged. Our findings suggest that the age at onset of alcohol consumption critically influences alcohol intake, particularly in males. Additionally, females consistently showed higher alcohol intake regardless of age, highlighting inherent sex-specific differences. The dynamic changes in catalase activity and opioid receptor expression suggest the involvement of these factors in modulating alcohol consumption.
饮酒会导致显著的神经化学和神经生物学变化，从而导致酒精使用障碍（AUD）的发展，根据临床数据，AUD 表现出性别和年龄依赖性的差异。然而，在研究饮酒模式时，临床前研究往往忽略了这些因素。在这项研究中，我们提供了连续一个月暴露于 20%乙醇溶液的雄性和雌性大鼠的数据。根据开始饮酒时的年龄（8 周和 12 周），将动物分为两组。有趣的是，12 周龄雄性的饮酒量明显少于 12 周龄雌性和 8 周龄动物，表明我们的模型中饮酒模式随性别和年龄而变化。此外，为了深入研究乙醇摄入在中脑边缘系统（MCLS）中引起的神经生物学改变，这些改变可能参与其强化特性和维持饮酒行为，我们测量了这些动物伏隔核（NAc）中参与酒精代谢并与乙醇强化相关的过氧化氢酶活性。此外，我们测量了 NAc 中 mu（MOR）、kappa（KOR）、delta（DOR）和 nociceptin（NOP）阿片受体的水平，因为内源性阿片能系统在调节 MCLS 和酒精强化方面发挥着关键作用。MOR 水平在高饮酒组（8 周龄雄性和所有雌性）中较低。DOR 和 NOP 水平随年龄而降低，而 KOR 水平保持不变。我们的研究结果表明，饮酒开始的年龄会严重影响饮酒量，特别是在男性中。此外，女性无论年龄大小，饮酒量始终较高，突出了内在的性别特异性差异。过氧化氢酶活性和阿片受体表达的动态变化表明这些因素参与了调节饮酒量。
