Melendez Roberto I, Rodd-Henricks Zachary A, Engleman Eric A, Li Ting-Kai, McBride William J, Murphy James M
Department of Psychology, Program in Psychobiology of Addictions, Purdue School of Science/IUPUI, 402 N. Blackford Street, Indianapolis, Indiana 46202-3275, USA.
Alcohol Clin Exp Res. 2002 Mar;26(3):318-25.
The present study was designed to test directly whether a contextual stimulus for access to ethanol would acquire the ability to enhance locomotor activity and dopamine efflux in the nucleus accumbens (NAc) of alcohol-preferring (P) rats. The study also explored the association between elevated locomotor activity and NAc dopamine efflux during operant self-administration of ethanol.
Adult female P rats were randomly assigned to operantly self-administer either 15% (v/v) ethanol or 0.0125% (w/v) saccharin. Both groups were trained in a daily 30-min two-lever concurrent operant task (FR-3) to orally self-administer ethanol or saccharin, with water on the alternate lever. A third (control) group was trained to self-administer water on both levers. All groups were also acclimated in the operant chambers to periods of habituation, anticipation, and postadministration.
Compared with controls, the ethanol group, but not the saccharin group, showed significant increases in locomotor activity as well as increased NAc dopamine efflux during the first 10 min of the anticipation period. During the first 10 min of the self-administration period, locomotor activity was significantly increased in both the ethanol and saccharin groups compared with control values. The ethanol group, but not the saccharin group, showed significant increases in NAc dopamine efflux during the 20th and 30th min of the self-administration period and during the first 10 min of the postadministration period.
The findings suggest that acquisition of signal-induced anticipation of self-administered ethanol is associated with increases in locomotor activity and extracellular levels of dopamine in the NAc of P rats. Such associations may be important to the development and maintenance of ethanol-seeking behaviors. The findings also indicate that operant self-administration of ethanol is associated with increases in extracellular levels of dopamine in the NAc of P rats.
本研究旨在直接测试获取乙醇的情境刺激是否会获得增强偏爱酒精（P）大鼠伏隔核（NAc）中运动活动和多巴胺外流的能力。该研究还探讨了在乙醇操作性自我给药过程中运动活动增强与NAc多巴胺外流之间的关联。
成年雌性P大鼠被随机分配以操作性方式自我给药15%（v/v）乙醇或0.0125%（w/v）糖精。两组均接受每日30分钟的双杠杆同时操作性任务（FR-3）训练，以口服方式自我给药乙醇或糖精，另一杠杆提供水。第三组（对照组）接受在两个杠杆上均自我给水的训练。所有组还在操作箱中适应习惯化、预期和给药后阶段。
与对照组相比，乙醇组而非糖精组在预期期的前10分钟内运动活动显著增加，同时NAc多巴胺外流也增加。在自我给药期的前10分钟内，乙醇组和糖精组的运动活动均较对照值显著增加。乙醇组而非糖精组在自我给药期的第20和30分钟以及给药后阶段的前10分钟内NAc多巴胺外流显著增加。
研究结果表明，信号诱导的自我给药乙醇预期的获得与P大鼠NAc中运动活动增加和多巴胺细胞外水平升高相关。这种关联可能对寻求乙醇行为的发展和维持很重要。研究结果还表明，乙醇的操作性自我给药与P大鼠NAc中多巴胺细胞外水平升高相关。
