Colom-Rocha Carles, Bis-Humbert Cristian, García-Fuster M Julia
University Research Institute of Health Sciences, University of the Balearic Islands, Palma, Spain.
Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain.
Front Pharmacol. 2024 Aug 27;15:1448170. doi: 10.3389/fphar.2024.1448170. eCollection 2024.
Few studies have previously evaluated the long-term impact of initiating the combined use of alcohol and cocaine early-in-life during adolescence. Our preclinical study characterized changes in affective-like behavior and/or voluntary ethanol consumption emerging later on in adulthood induced by a prior adolescent drug exposure, as well as tested therapeutical interventions (i.e., cannabidiol or ketamine) to prevent the observed effects.
We performed three independent studies with male and female Sprague-Dawley rats, treated in adolescence (postnatal days, PND 29-38) with non-contingent paradigms of ethanol, cocaine, their combination or vehicle. Later on, adult rats were (1) scored for their affective-like state (forced-swim, elevated-plus maze, novelty-suppressed feeding, sucrose preference), (2) allowed to freely drink ethanol for 6 weeks (two-bottle choice), or (3) treated with cannabidiol or ketamine before given access to ethanol in adulthood.
No signs of increased negative affect were observed in adulthood following the adolescent treatments. However, adolescent ethanol exposure was a risk-factor for later developing an increased voluntary ethanol consumption in adulthood, both for male and female rats. This risk was similar when ethanol was combined with adolescent cocaine exposure, since cocaine alone showed no effects on later ethanol intake. Finally, rats exposed to adolescent ethanol and pretreated in adulthood with cannabidiol (and/or ketamine, but just for females) reduced their ethanol voluntary consumption.
Our data provided two therapeutical options capable of preventing the impact of an early drug initiation during adolescence by decreasing voluntary ethanol consumption in adult rats.
此前很少有研究评估青少年时期过早开始同时使用酒精和可卡因的长期影响。我们的临床前研究描述了先前青少年期药物暴露在成年后期引发的情感样行为变化和/或自愿乙醇摄入量变化，并测试了治疗干预措施（即大麻二酚或氯胺酮）以预防所观察到的影响。
我们对雄性和雌性斯普拉格-道利大鼠进行了三项独立研究，在青少年期（出生后第29 - 38天）用非条件范式给予乙醇、可卡因、它们的组合或赋形剂处理。随后，成年大鼠进行如下操作：(1) 对其情感样状态进行评分（强迫游泳、高架十字迷宫、新奇抑制摄食、蔗糖偏好）；(2) 允许自由饮用乙醇6周（双瓶选择）；或者(3) 在成年期给予乙醇之前用大麻二酚或氯胺酮进行处理。
青少年期处理后成年大鼠未观察到负面影响增加的迹象。然而，青少年期乙醇暴露是成年期雄性和雌性大鼠后期自愿乙醇摄入量增加的一个风险因素。当乙醇与青少年期可卡因暴露联合使用时，这种风险相似，因为单独使用可卡因对后期乙醇摄入量没有影响。最后，暴露于青少年期乙醇且在成年期用大麻二酚预处理（和/或氯胺酮，但仅对雌性大鼠）的大鼠减少了它们的自愿乙醇摄入量。
我们的数据提供了两种治疗选择，能够通过减少成年大鼠的自愿乙醇摄入量来预防青少年期过早开始使用药物的影响。
