Background SKF83959, an atypical dopamine (DA) D1 receptor agonist, has been used to test the functions of DA-related receptor complexes in vitro, but little is known about its impact on conditioned behavior. The present study examined the effects of SKF83959 on operant behaviors and assayed the neurochemical mechanisms involved. Methods Male rats were trained and maintained on either a fixed-interval 30-second (FI30) schedule or a differential reinforcement of low-rate response 10-second (DRL10) schedule of reinforcement. After drug treatment tests, western blotting assayed the protein expressions of the calcium-/calmodulin-dependent protein kinase II (CaMKII) and the transcription factor cyclic AMP response element binding protein (CREB) in tissues collected from 4 selected DA-related areas. Results SKF83959 disrupted the performance of FI30 and DRL10 behaviors in a dose-dependent manner by reducing the total number of responses in varying magnitudes. Moreover, the distinct profiles of the behavior altered by the drug were manifested by analyzing qualitative and quantitative measures on both tasks. Western-blot results showed that phospho-CaMKII levels decreased in the nucleus accumbens and the dorsal striatum of the drug-treated FI30 and DRL10 subjects, respectively, compared with their vehicle controls. The phospho-CREB levels decreased in the nucleus accumbens and the hippocampus of drug-treated FI30 subjects but increased in the nucleus accumbens of drug-treated DRL10 subjects. Conclusions Our results provide important insight into the neuropsychopharmacology of SKF83959, indicating that the drug-altered operant behavior is task dependent and related to regional-dependent changes of CaMKII-CREB signaling in the mesocorticolimbic DA systems.

中文翻译：

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SKF83959 对与纹状体亚区 CaMKII 信号明显变化相关的操作行为的任务依赖性影响

背景 SKF83959 是一种非典型多巴胺 (DA) D1 受体激动剂，已用于体外测试 DA 相关受体复合物的功能，但对其对条件行为的影响知之甚少。本研究检查了 SKF83959 对操作行为的影响，并分析了所涉及的神经化学机制。方法 雄性大鼠被训练和维持在固定间隔 30 秒 (FI30) 计划或低速率反应 10 秒 (DRL10) 强化计划的差异强化。在药物治疗测试后，蛋白质印迹法检测了从 4 个选定的 DA 相关区域收集的组织中钙/钙调蛋白依赖性蛋白激酶 II (CaMKII) 和转录因子环 AMP 反应元件结合蛋白 (CREB) 的蛋白质表达。结果 SKF83959 通过减少不同幅度的反应总数，以剂量依赖性方式破坏了 FI30 和 DRL10 行为的表现。此外，通过分析这两项任务的定性和定量措施，可以显示出药物改变的行为的不同特征。Western-blot 结果显示，与载体对照相比，药物治疗的 FI30 和 DRL10 受试者的伏隔核和背侧纹状体中的磷酸化 CaMKII 水平分别降低。药物治疗的 FI30 受试者的伏隔核和海马中的磷酸化 CREB ​​水平降低，但药物治疗的 DRL10 受试者的伏隔核中的磷酸化 CREB ​​水平升高。结论 我们的结果提供了对 SKF83959 的神经精神药理学的重要见解，