Péczely László, Ollmann Tamás, László Kristóf, Kovács Anita, Gálosi Rita, Szabó Ádám, Karádi Zoltán, Lénárd László
Institute of Physiology, Pécs University Medical School, Szigeti str. 12, P.O. Box 99, H-7602 Pécs, Hungary.
Institute of Physiology, Pécs University Medical School, Szigeti str. 12, P.O. Box 99, H-7602 Pécs, Hungary; Molecular Neurophysiology Research Group, Pécs University, Szentágothai Research Center, Pécs, Hungary.
Behav Brain Res. 2014 Aug 15;270:131-6. doi: 10.1016/j.bbr.2014.04.054. Epub 2014 May 9.
The mesolimbic dopaminergic system (MLDS) originating from the ventral tegmental area has important role in the regulation of motivation, learning and memory. The ventral pallidum (VP), innervated by the MLDS, is involved in the regulation of adaptive behavior, but its exact role is not known in inhibitory avoidance learning. The VP contains both D1 and D2 dopamine receptors, but the density of the former subtype is more excessive. Therefore, in our present experiments, the role of D1 dopamine receptors of the VP in one trial step-through inhibitory avoidance paradigm was investigated. In the conditioning trial, animals were shocked 3 times with 0.5 mA current for 1s, and subsequently were microinjected bilaterally with D1 dopamine receptor agonist SKF38393 into the VP in three doses (0.1 μg, 1.0 μg or 5.0 μg in 0.4 μl saline). To clarify whether the agonist effect was specific, we also applied the D1 dopamine receptor antagonist SCH23390 (5.0 μg in 0.4 μl saline) 15 min prior the agonist treatment. The D1 dopamine receptor agonist, in a dose-dependent manner, significantly increased the step-through latency during the test trials: retention was significant relative to the controls even after 2 weeks of conditioning. The D1 dopamine receptor antagonist SCH23390 pretreatment eliminated SKF38393 effects in the ventral pallidum. Our results show that D1 dopamine receptor mediated mechanisms in the VP facilitate learning and memory in inhibitory avoidance paradigm and this facilitation is specific because it can be eliminated by D1 dopamine receptor antagonist.
起源于腹侧被盖区的中脑边缘多巴胺能系统（MLDS）在动机、学习和记忆的调节中发挥着重要作用。受MLDS支配的腹侧苍白球（VP）参与适应性行为的调节，但其在抑制性回避学习中的具体作用尚不清楚。VP同时含有D1和D2多巴胺受体，但前一种亚型的密度更高。因此，在我们目前的实验中，研究了VP中D1多巴胺受体在单次试验穿梭抑制性回避范式中的作用。在条件试验中，动物接受3次0.5 mA电流、持续1秒的电击，随后以三种剂量（0.1 μg、1.0 μg或5.0 μg溶于0.4 μl生理盐水中）双侧向VP微量注射D1多巴胺受体激动剂SKF38393。为了阐明激动剂效应是否具有特异性，我们还在激动剂治疗前15分钟应用了D1多巴胺受体拮抗剂SCH23390（5.0 μg溶于0.4 μl生理盐水中）。D1多巴胺受体激动剂以剂量依赖的方式显著增加了测试试验中的穿梭潜伏期：即使在条件训练2周后，相对于对照组，记忆保持仍很显著。D1多巴胺受体拮抗剂SCH23390预处理消除了腹侧苍白球中SKF38393的作用。我们的结果表明，VP中D1多巴胺受体介导的机制促进了抑制性回避范式中的学习和记忆，并且这种促进作用具有特异性，因为它可以被D1多巴胺受体拮抗剂消除。
