Nicola S M, Kombian S B, Malenka R C
Graduate Program in Neuroscience, University of California, San Francisco 94143, USA.
J Neurosci. 1996 Mar 1;16(5):1591-604. doi: 10.1523/JNEUROSCI.16-05-01591.1996.
The effects of dopamine (DA) and the psychostimulants cocaine and amphetamine on excitatory transmission in the nucleus accumbens (NAc) were examined in rat NAc slices using both extracellular-field and whole-cell patch-clamp recording. DA, cocaine, and amphetamine reversibly reduced the excitatory synaptic responses (EPSPs/EPSCs) elicited by stimulation of prelimbic cortical afferents. DA and amphetamine increased paired-pulse facilitation, reduced the frequency of spontaneous miniature EPSCs (mEPSCs), and had no effect on mEPSC amplitude, suggesting a presynaptic mechanism for the observed reduction in excitatory synaptic transmission. The effects of DA and amphetamine were attenuated by the D1 receptor antagonist SCH23390 but not by the D2 receptor antagonist sulpiride. The broad-spectrum DA receptor agonist 6,7-ADTN mimicked the effects of DA and the psychostimulants, but neither the D1 receptor agonists SKF38393 and SKF81297 nor the D2 receptor agonist quinpirole caused a significant reduction in EPSP magnitude. SKF38393 at a higher concentration (100 microM) was effective in reducing the EPSP, however, and this reduction was sensitive to SCH23390. There was no difference in the effects of DA in cells from mutant mice lacking D1a receptors and cells from wild-type control mice. Unilaterally lesioning the dopaminergic afferents to the NAc using 6-hydroxydopamine attenuated the amphetamine-induced reduction in EPSP magnitude in slices from the lesioned hemisphere but not the control (unlesioned) hemisphere. These results indicate that DA and psychostimulants (acting indirectly by increasing endogenous extracellular DA levels) reduce excitatory synaptic transmission in the NAc by activating presynaptic DA receptors with D1-like properties.
运用细胞外场记录和全细胞膜片钳记录技术，在大鼠伏隔核（NAc）脑片中研究了多巴胺（DA）以及精神兴奋剂可卡因和苯丙胺对伏隔核兴奋性突触传递的影响。DA、可卡因和苯丙胺可逆性地降低了刺激前边缘皮质传入纤维所引发的兴奋性突触反应（兴奋性突触后电位/EPSCs）。DA和苯丙胺增加了双脉冲易化，降低了自发性微小兴奋性突触后电流（mEPSCs）的频率，且对mEPSC幅度无影响，提示观察到的兴奋性突触传递减少存在突触前机制。DA和苯丙胺的作用被D1受体拮抗剂SCH23390减弱，但未被D2受体拮抗剂舒必利减弱。广谱DA受体激动剂6,7 - ADTN模拟了DA和精神兴奋剂的作用，但D1受体激动剂SKF38393和SKF81297以及D2受体激动剂喹吡罗均未引起EPSP幅度的显著降低。然而，较高浓度（100 microM）的SKF38393可有效降低EPSP，且这种降低对SCH23390敏感。在缺乏D1a受体的突变小鼠细胞和野生型对照小鼠细胞中，DA的作用没有差异。使用6 - 羟基多巴胺单侧损毁伏隔核的多巴胺能传入纤维，减弱了苯丙胺诱导的损毁侧半球脑片EPSP幅度的降低，但对照（未损毁）半球未受影响。这些结果表明，DA和精神兴奋剂（通过增加内源性细胞外DA水平间接起作用）通过激活具有D1样特性的突触前DA受体来降低伏隔核中的兴奋性突触传递。
