Doyon William M, York Jennifer L, Diaz Laurea M, Samson Herman H, Czachowski Cristine L, Gonzales Rueben A
Division of Pharmacology, College of Pharmacy, University of Texas, Austin, Texas 78712, USA.
Alcohol Clin Exp Res. 2003 Oct;27(10):1573-82. doi: 10.1097/01.ALC.0000089959.66222.B8.
BACKGROUND This present study was designed to clarify the role of dopamine in the nucleus accumbens during operant ethanol self-administration by separating bar pressing (ethanol seeking) from ethanol consumption. Furthermore, we sought to define the relationship between ethanol in the brain and the accumbal dopamine response after oral self-administration of ethanol.
Two separate groups of male Long-Evans rats were trained to bar press with 10% ethanol or water. Rats were trained to elicit an escalating number of bar presses across daily sessions before gaining access to the drinking solution for 20 min. Microdialysis was performed before (during a waiting period), during, and after bar pressing and drinking. A handling control group was included, but did not receive training.
A significant increase in dopamine occurred during placement of the rats into the operant chamber in trained rats and handling controls. The lever-pressing period did not produce an increase in dialysate dopamine. Accumbal dopamine was increased in the first 5 min of ethanol, but not water, consumption. Ethanol appeared in the dialysate sample following ethanol availability, and peak concentrations were reached at 10 min. Most of the ethanol and water consumption occurred within 5 min of fluid access. The probes were distributed in the core (32%), shell (32%), and core plus shell (36%) regions of the nucleus accumbens.
The enhancement of dopamine during transfer into the operant chamber does not depend on anticipation or operant training with ethanol or water reinforcement. Furthermore, the difference between the time course of accumbal dopamine and ethanol in dialysates suggests that the dopamine response is not solely due to pharmacological effects of ethanol. The dopamine response may be associated with the stimulus properties of ethanol presentation, which would be strongest during consumption.
背景 本研究旨在通过将压杆行为(寻找乙醇)与乙醇消耗分开,阐明伏隔核中多巴胺在操作性乙醇自我给药过程中的作用。此外,我们试图确定口服自我给药乙醇后大脑中的乙醇与伏隔核多巴胺反应之间的关系。
将两组雄性Long-Evans大鼠分别训练用10%乙醇或水进行压杆。在大鼠获得20分钟饮用溶液之前,每天训练它们增加压杆次数。在压杆和饮水前(等待期)、期间和之后进行微透析。纳入了一个处理对照组,但该组未接受训练。
在训练大鼠和处理对照组中,将大鼠放入操作性实验箱时多巴胺显著增加。压杆期间透析液中的多巴胺没有增加。在乙醇(而非水)消耗的前5分钟,伏隔核多巴胺增加。乙醇供应后出现在透析液样本中,10分钟时达到峰值浓度。大多数乙醇和水的消耗发生在获得液体后的5分钟内。探针分布在伏隔核的核心(32%)、壳(32%)和核心加壳(36%)区域。
转移到操作性实验箱期间多巴胺的增强不依赖于对乙醇或水强化的预期或操作性训练。此外,伏隔核多巴胺和透析液中乙醇时间进程的差异表明,多巴胺反应并非仅由乙醇的药理作用引起。多巴胺反应可能与乙醇呈现的刺激特性有关,在消耗期间这种刺激特性最强。