Midgley L P, Bush L G, Gibb J W, Hanson G R
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City.
J Pharmacol Exp Ther. 1993 Nov;267(2):707-13.
Neuropeptide Y-like immunoreactivity (NPYLI) in the frontal cortex and nucleus accumbens was significantly decreased after acute and multiple administrations of phencyclidine-HCl (PCP). The role of dopamine, serotonin and sigma receptors in these PCP-induced effects was evaluated. Neither the dopamine D1 antagonist SCH 23390 nor the D2 antagonist sulpiride by itself altered cortical neuropeptide systems, but in combination they totally blocked the PCP-induced changes. In contrast, sulpiride alone significantly decreased accumbens NPYLI content and enhanced the PCP-induced decreases, whereas SCH 23390 alone had no effect on accumbens NPYLI levels but did attenuate PCP-induced effects. Neither depletion of serotonin nor blockage of the sigma "receptor" had any effect on PCP-induced changes in either structure. The effects of the selective, noncompetitive N-methyl-D-aspartate receptor antagonist MK-801 on cortical and accumbens NPYLI content were similar to those of PCP, suggesting an N-methyl-D-aspartate receptor mechanism in these effects. Administration of gamma-aminobutyric acid-transaminase (GABA-T) inhibitors, gamma-vinyl-GABA (GVG, vigabatrin, MDL 71,754) or aminooxyacetic acid alone had no effect on cortical NPYLI content; however, administration of aminooxyacetic acid alone decreased accumbens NPYLI levels. Co-administration of these GABA-T inhibitors with PCP completely blocked PCP-induced cortical NPYLI decreases and attenuated NPYLI changes in the accumbens. These data suggest that limbic neuropeptide systems are differentially modulated by N-methyl-D-aspartate and dopaminergic activity and that glutamatergic influences on cortical and accumbens NPY systems are mediated, at least in part, by GABAergic mechanisms.
盐酸苯环利定（PCP）急性给药和多次给药后，额叶皮质和伏隔核中的神经肽Y样免疫反应性（NPYLI）显著降低。评估了多巴胺、5-羟色胺和西格玛受体在这些PCP诱导效应中的作用。多巴胺D1拮抗剂SCH 23390和D2拮抗剂舒必利单独使用时均未改变皮质神经肽系统，但联合使用时它们完全阻断了PCP诱导的变化。相比之下，单独使用舒必利可显著降低伏隔核NPYLI含量并增强PCP诱导的降低作用，而单独使用SCH 23390对伏隔核NPYLI水平无影响，但可减弱PCP诱导的效应。5-羟色胺耗竭或西格玛“受体”阻断对这两种结构中PCP诱导的变化均无任何影响。选择性、非竞争性N-甲基-D-天冬氨酸受体拮抗剂MK-801对皮质和伏隔核NPYLI含量的影响与PCP相似，表明这些效应中存在N-甲基-D-天冬氨酸受体机制。单独给予γ-氨基丁酸转氨酶（GABA-T）抑制剂γ-乙烯基-GABA（GVG，vigabatrin，MDL 71,754）或氨氧乙酸对皮质NPYLI含量无影响；然而，单独给予氨氧乙酸可降低伏隔核NPYLI水平。这些GABA-T抑制剂与PCP联合给药可完全阻断PCP诱导的皮质NPYLI降低，并减弱伏隔核中的NPYLI变化。这些数据表明，边缘神经肽系统受到N-甲基-D-天冬氨酸和多巴胺能活性的差异调节，并且谷氨酸能对皮质和伏隔核NPY系统的影响至少部分是由GABA能机制介导的。
