Pirot S, Godbout R, Mantz J, Tassin J P, Glowinski J, Thierry A M
INSERM U114, Chaire de Neuropharmacologie, Collège de France, Paris.
Neuroscience. 1992 Aug;49(4):857-65. doi: 10.1016/0306-4522(92)90362-6.
The medial prefrontal cortex of the rat receives dopamine and non-dopaminergic projections from the ventral tegmental area. Both electrical stimulation of the ventral tegmental area and local application of dopamine induce an inhibition of the spontaneous activity of most prefrontal cortical neurons, including efferent neurons. In the present study, the techniques of extracellular recording and microiontophoresis were used in anesthetized rats in order to determine whether these dopamine- and ventral tegmental area-induced inhibitory responses involve GABAergic components. Prefrontal cortex output neurons were identified by antidromic activation from subcortical structures. The inhibitory responses evoked by the local application of dopamine were blocked by the iontophoretic application of the D2 antagonist sulpiride, and the GABAA antagonist bicuculline in 89 and 57% of the cases, respectively. In addition, sulpiride and bicuculline abolished the inhibition induced by ventral tegmental area stimulation in 54 and 51% of the prefrontal cortical cells tested, respectively. The implication of a non-dopaminergic mesocortical system in the ventral tegmental area-induced inhibition was further analysed using rats pre-treated with alpha-methylparatyrosine to deplete dopamine stores. The proportion of prefrontal cortical cells inhibited by ventral tegmental area stimulation was markedly reduced (39%) in alpha-methylparatyrosine-treated rats, when compared to controls (86%). Remaining ventral tegmental area-induced inhibition was no longer affected by sulpiride, but in all cases blocked by the local microiontophoretic application of bicuculline. The present results suggest that: (1) the dopamine-induced inhibition of prefrontal cortex neurons could involve cortical GABAergic interneurones; (2) the non-dopaminergic mesocortical system exerts also an inhibitory influence on prefrontal cortical cells and appears to be GABAergic.
大鼠的内侧前额叶皮质接受来自腹侧被盖区的多巴胺能和非多巴胺能投射。对腹侧被盖区的电刺激以及多巴胺的局部应用均会抑制大多数前额叶皮质神经元（包括传出神经元）的自发活动。在本研究中，对麻醉的大鼠使用细胞外记录和微离子透入技术，以确定这些多巴胺和腹侧被盖区诱导的抑制反应是否涉及γ-氨基丁酸（GABA）能成分。通过皮层下结构的逆向激活来识别前额叶皮质输出神经元。多巴胺局部应用所诱发的抑制反应，分别在89%和57%的情况下被离子透入应用D2拮抗剂舒必利和GABAA拮抗剂荷包牡丹碱阻断。此外，舒必利和荷包牡丹碱分别使54%和51%接受测试的前额叶皮质细胞中腹侧被盖区刺激所诱导的抑制作用消失。使用α-甲基对酪氨酸预处理以耗尽多巴胺储备的大鼠，进一步分析了腹侧被盖区诱导的抑制中，非多巴胺能中皮质系统的作用。与对照组（86%）相比，α-甲基对酪氨酸处理的大鼠中，腹侧被盖区刺激所抑制的前额叶皮质细胞比例显著降低（39%）。腹侧被盖区诱导的剩余抑制作用不再受舒必利影响，但在所有情况下均被局部微离子透入应用荷包牡丹碱阻断。目前的结果表明：（1）多巴胺对前额叶皮质神经元的抑制作用可能涉及皮质GABA能中间神经元；（2）非多巴胺能中皮质系统对前额叶皮质细胞也发挥抑制作用，且似乎是GABA能的。
