青春期和成年雄性Long-Evans大鼠对甜味乙醇的操作性自我给药及血液乙醇水平的时间进程
Operant self-administration of sweetened ethanol and time course of blood ethanol levels in adolescent and adult male Long-Evans rats.
作者信息
Doherty James M, Gonzales Rueben A
机构信息
Waggoner Center for Alcohol and Addiction Research , University of Texas at Austin, Austin, Texas; Department of Pharmacology , College of Pharmacy, University of Texas at Austin, Austin, Texas.
出版信息
Alcohol Clin Exp Res. 2015 Mar;39(3):485-95. doi: 10.1111/acer.12630. Epub 2015 Feb 19.
BACKGROUND
Little is known regarding mechanisms regulating ethanol (EtOH) self-administration during adolescence or if the mechanisms differ from adults. One of the best models of abuse liability is operant self-administration. Therefore, we characterized operant sweetened EtOH self-administration behavior in adolescent and adult rats.
METHODS
Adolescent (36 days old at first EtOH exposure) and adult male Long-Evans rats were first trained to self-administer 10% sucrose (10S) in an appetitive/consummatory operant model for 1 week, and then the drinking solution was switched to 10% sucrose plus 10% EtOH (10S10E) for 2 weeks. Next, rats were switched to a fixed ratio 2 schedule, and this was followed by 1 session using a progressive ratio schedule of reinforcement. Last, rats were tested for cue-induced reinstatement of lever-pressing behavior under extinction conditions after 13 days of abstinence. Blood EtOH concentration (BEC) of sweetened EtOH (self-administered or intragastric [IG] administration of 1 g/kg) was determined via gas chromatography. Control rats drank only 10S.
RESULTS
Consumption of sweetened EtOH was not different between adolescents and adults under any schedule tested, reaching 1 g/kg in 20 minutes in the appetitive/consummatory model. Appetitive behavior directed at sweetened EtOH was less focused in adolescents versus adults. No age differences were found in motivation for sweetened EtOH. Cue-induced reinstatement of EtOH-seeking behavior after abstinence also did not differ by age. In control groups, no age difference was found in appetitive behavior or the amount of sucrose consumed, although adults exhibited greater cue-induced reinstatement. BEC after self-administration or IG administration of sweetened EtOH was higher in adults than adolescents.
CONCLUSIONS
Consumption and motivation for sweetened EtOH are similar in adolescents and adults, although adolescents are more vulnerable to the effects of EtOH consumption on appetitive behavior. The IG results suggest larger volume of distribution and higher first-pass metabolism of sweetened EtOH in adolescents versus adults, which may limit the reinforcing effects of EtOH in some adolescents. Overall, we have begun to establish an operant sweetened EtOH self-administration model in adolescent rats.
背景
关于青春期乙醇（EtOH）自我给药的调节机制，或者这些机制是否与成年人不同，目前所知甚少。滥用倾向的最佳模型之一是操作性自我给药。因此，我们对青春期和成年大鼠的操作性甜味EtOH自我给药行为进行了表征。
方法
青春期（首次接触EtOH时36日龄）和成年雄性Long-Evans大鼠首先在一个食欲/消耗性操作性模型中接受训练，以自我给药10%的蔗糖（10S），为期1周，然后将饮用溶液换成10%的蔗糖加10%的EtOH（10S10E），持续2周。接下来，大鼠切换到固定比例2的程序，随后进行1次使用渐进比例强化程序的实验。最后，在禁欲13天后，对大鼠在消退条件下提示诱导的压杆行为恢复情况进行测试。通过气相色谱法测定甜味EtOH（自我给药或胃内[IG]注射1 g/kg）的血液EtOH浓度（BEC）。对照大鼠只饮用10S。
结果
在任何测试程序下，青春期和成年大鼠对甜味EtOH的消耗量没有差异，在食欲/消耗性模型中20分钟内达到1 g/kg。与成年大鼠相比，青春期大鼠针对甜味EtOH的食欲行为不太集中。在对甜味EtOH的动机方面未发现年龄差异。禁欲后提示诱导的EtOH寻求行为恢复在年龄上也没有差异。在对照组中，虽然成年大鼠表现出更大的提示诱导恢复，但在食欲行为或蔗糖消耗量方面未发现年龄差异。自我给药或IG注射甜味EtOH后，成年大鼠的BEC高于青春期大鼠。
结论
青春期和成年大鼠对甜味EtOH的消耗量和动机相似，尽管青春期大鼠更容易受到EtOH消耗对食欲行为的影响。IG实验结果表明，与成年大鼠相比，青春期大鼠甜味EtOH的分布容积更大，首过代谢更高，这可能会限制EtOH在一些青春期大鼠中的强化作用。总体而言，我们已开始在青春期大鼠中建立操作性甜味EtOH自我给药模型。
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