Shapovalova K B, Kamkina Yu V
I. P. Pavlov Institute of Physiology, Russian Academy of Sciences, 6 Makarov Bank, 199034, St. Petersburg, Russia.
Neurosci Behav Physiol. 2008 Jan;38(1):71-9. doi: 10.1007/s11055-008-0010-6.
Studies on 60 Sprague-Dawley rats were performed to compare systemic and intrastriate administration of the selective D1 dopamine receptor blocker SCH23390 on the acquisition of a discriminant conditioned active avoidance reflex (CAAR) in a T maze and on behavior in an open field test. Systemic treatment at a dose of 0.025 mg/kg produced several-fold reductions in the proportion of correct performances of the discriminant CAAR and motor activity in the open field test. At the same time, bilateral microinjection of SCH23390 into the rat neostriatum at doses of 0.004-1.0 microg did not induce any deterioration in learning of the discriminant CAAR as compared with intact controls, though there was a sharp inhibition of motor activity in the open field test. Bilateral microinjections of the D2 dopamine receptor blocker raclopride into the rat neostriatum at a dose of 0.004 microg produced a marked and long-lasting degradation of learning of the discriminant CAAR. These data lead to the following conclusions: 1) the differences in the effects of systemic and intrastriate administration of SCH23390 appear to be associated with the fact that the behavioral changes seen after systemic administration may be mediated mainly by structures differing from neostriatal D1 receptors, and 2) the D1-mediated effects of the nigrostriatal dopaminergic system on the neostriatum are complex, with activation of motor activity (projection spiny neurons of the direct pathway) and weak modulation of the learning process (large aspiny cholinergic interneurons). Modulation of the learning process evidently occurs via neostriatal D2 dopaminergic receptors.
对60只Sprague-Dawley大鼠进行了研究，以比较选择性D1多巴胺受体阻滞剂SCH23390全身给药和纹状体内给药对T迷宫中辨别性条件性主动回避反射（CAAR）的习得以及旷场试验中行为的影响。0.025 mg/kg剂量的全身治疗使辨别性CAAR的正确表现比例和旷场试验中的运动活动降低了几倍。同时，与完整对照组相比，以0.004 - 1.0微克的剂量将SCH23390双侧微量注射到大鼠新纹状体中，在辨别性CAAR的学习方面并未引起任何恶化，尽管在旷场试验中运动活动受到了强烈抑制。以0.004微克的剂量将D2多巴胺受体阻滞剂雷氯必利双侧微量注射到大鼠新纹状体中，导致辨别性CAAR的学习出现明显且持久的退化。这些数据得出以下结论：1）SCH23390全身给药和纹状体内给药效果的差异似乎与以下事实有关，即全身给药后观察到的行为变化可能主要由不同于新纹状体D1受体的结构介导；2）黑质纹状体多巴胺能系统对新纹状体的D1介导作用是复杂的，包括运动活动的激活（直接通路的投射棘状神经元）和对学习过程的微弱调节（大型无棘胆碱能中间神经元）。学习过程的调节显然是通过新纹状体D2多巴胺能受体发生的。
