Meador-Woodruff J H, King R E, Damask S P, Bovenkerk K A
Mental Health Research Institute, University of Michigan, Ann Arbor 48109-0720, USA.
Mol Psychiatry. 1996 Mar;1(1):41-53.
Dopamine-glutamate interactions within discrete neural circuits are increasingly recognized as potential substrates for dysregulation in schizophrenia, and as a result, potential targets for pharmacological intervention in this illness. We examined the regulation, by haloperidol (2 mg kg-1 day-1) and clozapine (20 mg kg-1 day-1), of the mRNAs encoding the four AMPA receptor subunits (gluR1-gluR4), three low-affinity kainate receptor subunits (gluR5-gluR7), and two high-affinity kainate subunits (KA1 and KA2) in the rat hippocampal formation and associated entorhinal cortex. A complex and differential pattern of AMPA and kainate subunit mRNA regulation by clozapine and haloperidol was observed in this study. Both drugs caused significant alterations of most of these mRNAs, but in a heterogeneous and region-specific fashion. These data suggest that these antipsychotic drugs alter the expression of the genes encoding the subunits that express ionotropic glutamate receptors. Given the importance of glutamatergic mechanisms and the hippocampal formation in schizophrenia, these data suggest a potential substrate for neurotransmitter dysregulation in this illness, as well as a potential target for therapeutic intervention.
离散神经回路中的多巴胺 - 谷氨酸相互作用日益被认为是精神分裂症失调的潜在基础，因此也是该疾病药物干预的潜在靶点。我们研究了氟哌啶醇（2毫克/千克/天）和氯氮平（20毫克/千克/天）对大鼠海马结构及相关内嗅皮质中编码四种AMPA受体亚基（gluR1 - gluR4）、三种低亲和力海人酸受体亚基（gluR5 - gluR7）和两种高亲和力海人酸亚基（KA1和KA2）的mRNA的调节作用。在本研究中观察到氯氮平和氟哌啶醇对AMPA和海人酸亚基mRNA的调节呈现出复杂且有差异的模式。两种药物均引起了这些mRNA中大多数的显著改变，但方式具有异质性且呈区域特异性。这些数据表明，这些抗精神病药物改变了编码离子型谷氨酸受体亚基的基因表达。鉴于谷氨酸能机制和海马结构在精神分裂症中的重要性，这些数据提示了该疾病中神经递质失调的潜在基础以及治疗干预的潜在靶点。
