Department of Psychology, University of Illinois at Urbana-Champaign, 515 Psychology Bldg MC-716, 603 E. Daniel St, Champaign, IL, 61820, USA.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 S. Limestone, Lexington, KY, 40536, USA.
Psychopharmacology (Berl). 2018 Mar;235(3):861-871. doi: 10.1007/s00213-017-4804-5. Epub 2017 Dec 2.
Adolescence is a period of considerable development of brain and behavior and is the time during which most drug use is initiated.
Age-dependent differences in motivated behaviors may be one of the factors that contribute to heightened vulnerability to developing substance use disorders, so we sought to compare age differences in methamphetamine (METH) and saccharin seeking.
Beginning during adolescence or adulthood, male and female Sprague-Dawley rats were trained to self-administer 0.1% saccharin (via liquid dipper cup) or intravenous METH at one of three doses (0.02, 0.05, 0.08 mg/kg/inf) under increasing fixed ratio schedules of reinforcement. Subsequently, responding for METH (0.02, 0.05, 0.08, or 0.1 mg/kg/inf) under progressive ratio response requirements was assessed in rats that acquired METH self-administration at the highest dose (0.08 mg/kg/inf).
We found that adult-onset rats acquired METH self-administration more readily and exhibited higher motivation compared to adolescent-onset rats, although there were no differences in METH intake during acquisition. Adult rats also acquired saccharin self-administration more readily, but in contrast to METH, there were age and sex differences in saccharin intake driven by high levels of responding in adult females.
These findings challenge the prevailing notion that adolescents are hypersensitive to reward and instead raise questions about the potential role of methodological factors on which rodent studies often differ.
青春期是大脑和行为发育的重要时期,也是大多数药物使用开始的时期。
动机行为的年龄依赖性差异可能是导致物质使用障碍易感性增加的因素之一,因此我们试图比较 methamphetamine(METH)和 saccharin 觅药的年龄差异。
从青春期或成年期开始,雄性和雌性 Sprague-Dawley 大鼠接受训练,通过液体滴杯自行摄取 0.1% saccharin(saccharin)或静脉内 METH,剂量为三个递增剂量(0.02、0.05、0.08mg/kg/inf),强化递增固定比率方案。随后,在以最高剂量(0.08mg/kg/inf)获得 METH 自我给药的大鼠中,评估了对 METH(0.02、0.05、0.08或 0.1mg/kg/inf)进行递增比率反应要求的反应。
我们发现,与青春期开始的大鼠相比,成年开始的大鼠更容易获得 METH 自我给药,并且表现出更高的动机,尽管在获得过程中 METH 摄入量没有差异。成年大鼠也更容易获得 saccharin 自我给药,但与 METH 相反,由于成年雌性大鼠的高反应水平,saccharin 摄入量存在年龄和性别差异。
这些发现挑战了青少年对奖励高度敏感的普遍观点,而是提出了关于啮齿动物研究中经常存在差异的方法学因素的潜在作用的问题。