Department of Pharmacy, Okayama University Hospital, 2-5-1, Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Behav Brain Res. 2013 Apr 15;243:313-21. doi: 10.1016/j.bbr.2012.10.051. Epub 2012 Nov 10.
It was recently demonstrated that the priming stimulation effect (PSE) in the runway model of intracranial self-stimulation (ICSS) can be used as a model system to study the motivational effects of drugs. However, the characteristics of this novel experimental model have not been fully clarified.
To elucidate the involvement of dopamine uptake inhibition in motivated behavior and the difference in experimental characteristics between closely related experimental models, we investigated the effects of the dopamine uptake inhibitor GBR12909 in the runway ICSS model, in the forced swimming test (FST), and on conditioned place preference (CPP). In addition, the role of dopamine receptor signaling in the runway model was evaluated using dopamine receptor agonists and antagonists.
GBR12909 dose-dependently increased running speed on the runway and decreased immobility time in the FST without affecting the time spent in the drug-associated compartment in CPP tests. The effect of GBR12909 in the runway model was inhibited by pre-treatment with the dopamine receptor antagonists haloperidol and raclopride. The dopamine receptor agonists SKF38393 and quinpirole dose-dependently decreased running speed.
These results demonstrate that GBR12909 displays motivation-enhancing and antidepressant-like effects without place conditioning effects. In addition, the mechanisms of PSE enhancement in the runway ICSS model are different from those underlying closely associated experimental models and are mediated by increases in dopamine signaling.
最近的研究表明，在颅内自我刺激（ICSS）的跑道模型中的启动刺激效应（PSE）可以作为一种研究药物动机效应的模型系统。然而，这个新颖的实验模型的特点尚未得到充分阐明。
为了阐明多巴胺摄取抑制在动机行为中的作用以及密切相关的实验模型之间实验特征的差异，我们研究了多巴胺摄取抑制剂 GBR12909 在跑道 ICSS 模型、强迫游泳试验（FST）和条件性位置偏好（CPP）中的作用。此外，还使用多巴胺受体激动剂和拮抗剂评估了多巴胺受体信号在跑道模型中的作用。
GBR12909 呈剂量依赖性地增加了跑道上的奔跑速度，并减少了 FST 中的不动时间，而不影响 CPP 测试中与药物相关的隔间中花费的时间。GBR12909 在跑道模型中的作用被多巴胺受体拮抗剂氟哌啶醇和氯丙嗪预处理所抑制。多巴胺受体激动剂 SKF38393 和喹吡罗尔呈剂量依赖性地降低了奔跑速度。
这些结果表明，GBR12909 具有增强动机和抗抑郁样作用，而没有位置条件作用。此外，跑道 ICSS 模型中 PSE 增强的机制与密切相关的实验模型不同，是通过增加多巴胺信号介导的。
