Pharmacological characterization of the receptor mediating electrophysiological responses to dopamine in the rat medial prefrontal cortex: a microiontophoretic study.
Pharmacological characterization of the receptor mediating electrophysiological responses to dopamine in the rat medial prefrontal cortex: a microiontophoretic study.
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发表时间：
1989-03
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通讯作者：
S. Sesack;B. Bunney
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作者：
S. Sesack;B. Bunney
采用细胞外单单位记录和微离子电泳技术对大鼠内侧前额叶皮质（PFC）中多巴胺（DA）抑制作用受体的药理学特征进行了表征。离子渗透应用DA抑制了PFC深层65%的自发活性细胞，而对浅层细胞的影响很小。D2选择性拮抗剂舒必利特异性地减弱了da诱导的对PFC深层神经元的抑制，而不阻断γ -氨基丁酸（GABA）或5-羟色胺（5-HT）的抑制作用。令人惊讶的是，舒必利的拮抗作用似乎并不具有立体特异性，因为它的(-)-和(+)-异构体在阻断DA的抑制作用方面同样有效。与舒必利相比，D1选择性拮抗剂SCH23390在减弱DA抑制反应方面的效果要差得多。选择性激动剂对da敏感的PFC神经元的作用也进行了研究。D2选择性激动剂LY171555和D1选择性激动剂SKF38393对少量da敏感的PFC神经元产生抑制作用。然而，大多数细胞仅被DA抑制，而不被LY171555或SKF38393抑制。此外，LY171555和SKF38393的离子电泳。此外，LY171555和SKF38393的离子导入未能抑制大多数da敏感的PFC细胞。LY171555，而不是SKF38393，在同时应用时显著减弱da诱导的抑制，表明D2选择性激动剂可能对该受体具有部分激动剂/弱拮抗剂活性。这些结果表明，在内侧PFC中介导DA抑制作用的受体具有D2亚型的药理学特征。然而，这种受体可能与大脑其他区域的D2位点不相同。
The pharmacological profile of the receptor mediating inhibitory effects of dopamine (DA) in the rat medial prefrontal cortex (PFC) was characterized using extracellular single unit recording and microiontophoretic techniques. Iontophoretic application of DA inhibited 65% of spontaneously active cells in the deep layers of the PFC, while producing little effect on cells in superficial laminae. The D2 selective antagonist, sulpiride, specifically attenuated DA-induced inhibition of deep layer PFC neurons, without blocking the inhibitory effects of gamma-aminobutyric acid (GABA) or serotonin (5-HT). Surprisingly, sulpiride antagonism did not appear to be stereospecific, as both its (-)- and (+)-isomers proved equally effective at blocking the inhibitory effects of DA. In contrast to sulpiride, the D1 selective antagonist, SCH23390, was much less effective at attenuating inhibitory responses to DA. The effects of selective agonists also were examined on DA-sensitive PFC neurons. The D2 selective agonist, LY171555, and the D1 selective agonist, SKF38393, produced inhibitory effects on a small number of DA-sensitive PFC neurons. However, the majority of cells tested were inhibited only by DA and not by LY171555 or SKF38393. In addition, coiontophoresis of LY171555 and SKF38393. In addition, coiontophoresis of LY171555 and SKF38393 failed to inhibit the majority of DA-sensitive PFC cells tested. LY171555, but not SKF38393, significantly attenuated DA-induced inhibition when applied simultaneously, suggesting that the D2 selective agonist might possess partial agonist/weak antagonist activity at this receptor. These results indicate that the receptor mediating the inhibitory effects of DA in the medial PFC has the pharmacological characteristics of a D2 subtype. However, this receptor may not be identical to D2 sites in other brain regions.