Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 SW Sam Jackson Park Road L470, Portland, OR, 97239, USA.
Psychopharmacology (Berl). 2021 Mar;238(3):899-911. doi: 10.1007/s00213-020-05741-3. Epub 2021 Jan 6.
The majority of preclinical studies assessing treatments for alcohol use disorder use singly housed animals. Because social factors affect ethanol intake, studies investigating such treatments in group-housed animals are needed.
We investigated the effects of repeated oxytocin treatment on ethanol intake in socially housed male and female C57BL/6J mice.
We used the novel "Herdsman" system implementing radiotracking technology to measure individual ethanol intake in group-housed animals. Mice were housed in same-sex groups of 4 per cage and exposed to 3 and 6% ethanol solutions. After baseline drinking was established, half of the animals in each cage received repeated intraperitoneal injections of 3 mg/kg oxytocin.
During baseline, females consumed more ethanol than males partly due to greater number of ethanol drinks taken by females. We also observed a gradual development of two peaks of ethanol consumption during the dark phase of the circadian cycle. The effects of oxytocin treatment were short-acting and varied across treatment days. Oxytocin significantly decreased ethanol intake on three out the four treatment days. On the fourth treatment day, oxytocin decreased ethanol intake and water intake.
The greater intake of ethanol in female mice is associated with the number of drinks taken. Oxytocin treatments not only cause an acute decrease in ethanol consumption, but can also change in efficacy over time. While the oxytocin system remains a promising therapeutic target for alcoholism, studies investigating longer periods of repeated oxytocin treatment and those using additional oxytocin receptor agonists are warranted.
大多数评估酒精使用障碍治疗方法的临床前研究都使用独居动物。由于社会因素会影响乙醇摄入量，因此需要在群居动物中研究此类治疗方法。
我们研究了重复给予催产素对群居雄性和雌性 C57BL/6J 小鼠乙醇摄入量的影响。
我们使用新的“牧人”系统实施放射跟踪技术来测量群居动物的个体乙醇摄入量。将小鼠以每笼 4 只为一组进行饲养，并暴露于 3%和 6%的乙醇溶液中。在建立基线饮酒后，每个笼子中的一半动物接受 3 毫克/千克催产素的重复腹腔内注射。
在基线期，雌性比雄性消耗更多的乙醇，部分原因是雌性摄入的乙醇饮料数量更多。我们还观察到在昼夜节律的暗期逐渐出现两个乙醇消耗高峰。催产素处理的效果是短暂的，并且在不同的处理日之间有所不同。催产素在 4 个处理日中的 3 天显著降低了乙醇摄入量。在第 4 天的处理日中，催产素降低了乙醇和水的摄入量。
雌性小鼠中更大的乙醇摄入量与摄入的饮料数量有关。催产素处理不仅会导致急性乙醇消耗减少，而且随着时间的推移其效果也会发生变化。虽然催产素系统仍然是治疗酒精中毒的有前途的治疗靶点，但需要进行更长时间的重复催产素治疗研究，并使用其他催产素受体激动剂进行研究。
