Glickstein Sara B, Desteno Deirdre A, Hof Patrick R, Schmauss Claudia
Department of Neuroscience, New York State Psychiatric Institute, New York 10032, USA.
Cereb Cortex. 2005 Jul;15(7):1016-24. doi: 10.1093/cercor/bhh202. Epub 2004 Nov 10.
Mice lacking dopamine D2 and D3 receptors and wildtype littermates were tested in a two-choice perceptual discrimination test that is dependent upon optimal functioning of the prefrontal cortex. Both mutants showed no deficits in attending to the perceptual stimuli or in shifting attention between stimulus dimensions. However, the performance of both mutants differed from the wildtype in different test phases. D2 mutants exhibited significant impairment in the first compound discrimination, indicating deficits in the initial acquisition of the task-governing rules. In contrast, D3 mutants performed significantly better in a set-shifting phase that required reversal learning. The higher response accuracy of D3 mutants was also accompanied by significantly increased response latency. A stereological assessment of test-induced expression of the c-fos gene in neurons of the anterior cingulate and prelimbic/infralimbic cortices revealed highest activation in D3 mutants, intermediate activation in wildtype and lowest activation in D2 mutants, indicating that response accuracy in the cognitive test correlates with the magnitude of prefrontal cortical activation regardless of which test phases revealed different performances. The study illustrates that dopamine differentially modulates prefrontal cortical activity during tasks requiring attention depending upon the type of D2-like receptor that is activated.
缺乏多巴胺 D2 和 D3 受体的小鼠及其野生型同窝小鼠在一项依赖于前额叶皮质最佳功能的二选一知觉辨别测试中接受了测试。两种突变体在关注知觉刺激或在刺激维度之间转移注意力方面均未表现出缺陷。然而，在不同的测试阶段，两种突变体的表现与野生型不同。D2 突变体在首次复合辨别中表现出显著损伤，表明在任务控制规则的初始习得方面存在缺陷。相比之下，D3 突变体在需要逆向学习的定势转换阶段表现得明显更好。D3 突变体较高的反应准确性还伴随着反应潜伏期的显著增加。对前扣带回和前边缘/下边缘皮质神经元中 c-fos 基因的测试诱导表达进行的立体学评估显示，D3 突变体的激活程度最高，野生型的激活程度中等，D2 突变体的激活程度最低，这表明认知测试中的反应准确性与前额叶皮质激活的程度相关，而与哪个测试阶段表现出不同的表现无关。该研究表明，在需要注意力的任务中，多巴胺根据被激活的 D2 样受体类型对前额叶皮质活动进行不同的调节。
