Broersen L M, Heinsbroek R P, de Bruin J P, Joosten R N, van Hest A, Olivier B
Graduate School Neurosciences Amsterdam, Netherlands Institute for Brain Research, The Netherlands.
Brain Res. 1994 May 9;645(1-2):113-22. doi: 10.1016/0006-8993(94)91644-6.
Lesions of the medial prefrontal cortex (mPFC) disrupt performance in a variety of delay tasks, which suggests that the mPFC supports short-term memory processes. The putative involvement of the dopaminergic innervation of the mPFC in these mnemonic processes was investigated by evaluating the effects of local infusions of dopaminergic drugs into the mPFC of rats in an operant delayed-matching-to-position (DMTP) task. Trained animals were provided with bilateral guide cannulae aimed at the dorsal part of the mPFC. Two separate groups of rats were tested after microinfusion of several doses of either the dopamine agonist apomorphine (APO) or the dopamine antagonist cis-flupenthixol (FLU). In addition, all animals were tested after infusion of several doses of the muscarinic antagonist scopolamine (SCO). Animals were tested 0 and 135 min after each infusion. At the 0 min interval, neither APO nor FLU affected accuracy of DMTP performance, while both drugs dose-dependently increased response latencies and decreased nosepoke frequencies. At the 135 min interval, APO had almost no effect, whereas the effects of FLU were very prominent. A number of animals no longer responded after infusion of the highest doses of FLU and those that did showed a delay-independent decrease in response accuracy. In contrast, SCO infusions into the mPFC induced a dose- and delay-dependent deterioration of DMTP performance. Taken together, these results support a direct involvement of the rat mPFC in short-term memory processes, although they implicate cholinergic rather than dopaminergic mechanisms in this function.
内侧前额叶皮质（mPFC）的损伤会破坏多种延迟任务的表现，这表明mPFC支持短期记忆过程。通过评估向大鼠mPFC局部注射多巴胺能药物对操作性位置延迟匹配（DMTP）任务的影响，研究了mPFC的多巴胺能神经支配在这些记忆过程中的假定作用。为经过训练的动物双侧植入靶向mPFC背侧的引导套管。在微量注射几剂多巴胺激动剂阿扑吗啡（APO）或多巴胺拮抗剂顺式氟哌噻吨（FLU）后，对两组不同的大鼠进行测试。此外，在注射几剂毒蕈碱拮抗剂东莨菪碱（SCO）后，对所有动物进行测试。在每次注射后0分钟和135分钟对动物进行测试。在0分钟间隔时，APO和FLU均未影响DMTP表现的准确性，而两种药物均剂量依赖性地增加反应潜伏期并降低鼻触频率。在135分钟间隔时，APO几乎没有影响，而FLU的影响非常显著。注射最高剂量的FLU后，许多动物不再做出反应，而那些做出反应的动物表现出与延迟无关的反应准确性下降。相比之下，向mPFC注射SCO会导致DMTP表现出现剂量和延迟依赖性恶化。综上所述，这些结果支持大鼠mPFC直接参与短期记忆过程，尽管它们表明该功能涉及胆碱能而非多巴胺能机制。
