Charara A, Grace A A
Departments of Neuroscience and Psychiatry, University of Pittsburgh, 446 Crawford Hall, Pittsburgh, PA 15260, USA.
Neuropsychopharmacology. 2003 Aug;28(8):1412-21. doi: 10.1038/sj.npp.1300220. Epub 2003 Jun 11.
The nucleus accumbens (NAc) receives excitatory afferents from several cortical and limbic regions and dense dopaminergic inputs from the ventral tegmental area. We examined the effects of dopamine (DA) D1 and D2 selective drugs on the responses evoked in the NAc shell neurons recorded in vitro by stimulation of hippocampal and amygdaloid afferents. Activation of hippocampal and amygdaloid afferents induced excitatory postsynaptic responses that were depressed by bath application of DA in most of the cells recorded. The DA effect was substantially blocked by the D1 receptor antagonist SCH 23390, but not by the D2 receptor antagonist eticlopride. Moreover, the D1 receptor agonist SKF 38393, but not the D2 receptor agonist quinpirole, mimicked the effects of DA, although a small population of neurons exhibited a D1-mediated facilitation of the EPSP amplitude following fornix stimulation. These data demonstrate a DA receptor subtype-specific modulation of glutamatergic inputs to the NAc, with D1 agonists attenuating amygdaloid inputs, whereas hippocampal-evoked responses were either depressed or potentiated by D1 stimulation. Such facilitation or attenuation of hippocampal afferents against a background of suppression of other afferents would permit the hippocampus to have a dominant influence over behavior during periods of exploration.
伏隔核(NAc)接收来自多个皮质和边缘区域的兴奋性传入纤维以及来自腹侧被盖区的密集多巴胺能输入。我们研究了多巴胺(DA)D1和D2选择性药物对体外记录的伏隔核壳神经元中由海马和杏仁核传入纤维刺激所诱发反应的影响。在大多数记录的细胞中,海马和杏仁核传入纤维的激活诱导了兴奋性突触后反应,而通过浴灌应用多巴胺可使这些反应受到抑制。多巴胺的这种作用被D1受体拮抗剂SCH 23390基本阻断,但未被D2受体拮抗剂依托必利阻断。此外,D1受体激动剂SKF 38393模拟了多巴胺的作用,而D2受体激动剂喹吡罗则没有,尽管有一小部分神经元在穹窿刺激后表现出D1介导的兴奋性突触后电位(EPSP)幅度增强。这些数据表明,多巴胺受体亚型对伏隔核的谷氨酸能输入具有特异性调节作用,D1激动剂减弱杏仁核输入,而D1刺激对海马诱发的反应则既有抑制作用也有增强作用。在其他传入纤维被抑制的背景下,海马传入纤维的这种增强或减弱作用将使海马在探索期间对行为产生主导影响。