Department of Psychiatry, University of Minnesota Medical School, MMC 392, Minneapolis, MN 55455, USA.
Psychopharmacology (Berl). 2013 May;227(2):243-50. doi: 10.1007/s00213-012-2958-8. Epub 2013 Jan 10.
Adolescence marks a period of increased vulnerability to the development of substance use disorders. High sweet preference is a genetically mediated behavioral trait that also predicts vulnerability to substances of abuse. Previous research has shown that while adolescent rats selectively bred for high (HiS) saccharin intake acquire cocaine self-administration at the same rate as adult HiS rats, adolescent rats bred for low saccharin intake (LoS) acquire cocaine self-administration faster than adult LoS rats.
This study was conducted to investigate the interaction of the addiction vulnerability factors of peri-adolescence and saccharin preference on cocaine intake using an animal model of escalation of cocaine consumption over 6-h/day sessions.
Peri-adolescent and adult HiS and LoS female rats self-administered i.v. cocaine (0.4 mg/kg/inf) during short-access (2-h/day) sessions for 2 days. Next, a long-access (6-h/day) period (LgA) commenced and lasted 16 days. Following LgA, session length was returned to 2-h/day for a second short access phase.
LoS peri-adolescent rats escalated cocaine intake over the LgA period and consumed more drug than LoS adult rats; however, peri-adolescent and adult HiS rats consumed similar amounts of cocaine during this period. Additionally, adult HiS rats self-administered more cocaine than adult LoS rats during the LgA period, while there was no phenotypic difference between the rat lines during peri-adolescence for the LgA period. During the first short-access phase, peri-adolescent rats self-administered more cocaine than adult rats.
These results emphasize the importance of adolescent drug abuse prevention by illustrating that phenotypic protection from addiction may not be expressed until adulthood.
青春期是易患物质使用障碍的时期。高甜偏好是一种遗传介导的行为特征,也预示着对滥用物质的易感性。先前的研究表明,虽然高糖精摄入(HiS)的青春期大鼠选择性繁殖,获得可卡因自我给药的速度与成年 HiS 大鼠相同,但低糖精摄入(LoS)的青春期大鼠获得可卡因自我给药的速度比成年 LoS 大鼠快。
本研究旨在使用可卡因消费递增的动物模型,研究青春期前和蔗糖偏好这两个成瘾易感性因素的相互作用对可卡因摄入的影响。
青春期和成年 HiS 和 LoS 雌性大鼠在 2 小时/天的短期访问(2 小时/天)期间进行静脉内可卡因(0.4mg/kg/inf)自我给药,共 2 天。然后,开始长期访问(6 小时/天),持续 16 天。在 LgA 之后,会话长度恢复到 2 小时/天,进行第二个短期访问阶段。
LoS 青春期大鼠在 LgA 期间可卡因摄入量增加,比 LoS 成年大鼠摄入更多的药物;然而,青春期和成年 HiS 大鼠在这段时间内摄入了相似量的可卡因。此外,成年 HiS 大鼠在 LgA 期间自我给药的可卡因量多于成年 LoS 大鼠,而在 LgA 期间,这两个大鼠品系之间没有表型差异。在第一个短期访问阶段,青春期大鼠自我给药的可卡因量多于成年大鼠。
这些结果强调了青少年药物滥用预防的重要性,说明成瘾的表型保护可能要到成年后才会表现出来。