Granon S, Passetti F, Thomas K L, Dalley J W, Everitt B J, Robbins T W
Department of Experimental Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom.
J Neurosci. 2000 Feb 1;20(3):1208-15. doi: 10.1523/JNEUROSCI.20-03-01208.2000.
The role in spatial divided and sustained attention of D1 and D2-like dopamine (DA) receptors in the rat prelimbic medial prefrontal cortex (mPFC) was investigated in a five-choice serial reaction time task. Rats were trained to detect brief flashes of light (0.5-0.25 sec) presented randomly in a spatial array of five apertures. When performance stabilized, animals received bilateral microinfusions of either the D1 DA receptor antagonist SCH 23390, the D1 DA receptor agonist SKF 38393, or the D2 DA antagonist sulpiride into the mPFC. Rats were divided into two groups, with low (<75% correct) and high (>75%) baseline levels of accuracy. Infusions of the D2 receptor antagonist sulpiride had no significant effect on any task variable. SCH 23390 (0.3 microg) selectively impaired the accuracy of attentional performance in rats in the high baseline condition. By contrast, SKF 38393 (0.06 microg) enhanced the accuracy of attentional performance in the low baseline condition, a lower dose (0.03 microg) also increasing the speed of making correct responses. Finally, the beneficial effects of SKF-383893 on choice accuracy were antagonized by SCH 23390 (1.0 microg). The results provide apparently the first demonstration of enhanced cognitive function after local administration of a D1 receptor agonist to the mPFC and suggest dissociable roles of D1 and D2 DA receptors of the mPFC in modulating attentional function.
在一项五选择连续反应时任务中,研究了大鼠前额叶内侧前额叶皮质(mPFC)中D1和D2样多巴胺(DA)受体在空间分离和持续注意力方面的作用。训练大鼠检测在五个小孔的空间阵列中随机呈现的短暂闪光(0.5 - 0.25秒)。当表现稳定后,动物接受双侧向mPFC微量注射D1 DA受体拮抗剂SCH 23390、D1 DA受体激动剂SKF 38393或D2 DA拮抗剂舒必利。大鼠被分为两组,基线准确率水平低(<75%正确)和高(>75%)。注射D2受体拮抗剂舒必利对任何任务变量均无显著影响。SCH 23390(0.3微克)选择性损害高基线条件下大鼠注意力表现的准确性。相比之下,SKF 38393(0.06微克)提高了低基线条件下注意力表现的准确性,较低剂量(0.03微克)也提高了做出正确反应的速度。最后,SKF - 383893对选择准确性的有益作用被SCH 23390(1.0微克)拮抗。结果显然首次证明了向mPFC局部施用D1受体激动剂后认知功能增强,并表明mPFC的D1和D2 DA受体在调节注意力功能方面具有可分离的作用。