Di Pietro N C, Seamans J K
Brain Research Centre, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.
Pharmacopsychiatry. 2007 Dec;40 Suppl 1:S27-33. doi: 10.1055/s-2007-992133.
Diminished activity within the prefrontal cortex (PFC) has been associated with many of the cognitive deficits that are observed in schizophrenia. It has been hypothesized that antipsychotic drugs (APDs) used to treat schizophrenia restore normal activity by antagonizing the dopamine (DA) D2 receptor, which is also known to modulate key ionic currents in the PFC. However, the hypothesis that an under-active cortical DA system is responsible for schizophrenic symptoms has been challenged by evidence that newer atypical APDs are weak antagonists at the D2 receptor but potent antagonists at the serotonin (5-HT) 2A receptor . This review examines how DA and 5-HT modulate cortical activity and how they may interact in ways that are relevant to schizophrenia. It is concluded that although D2 receptor antagonism remains a critical factor in restoring impaired cortical activity, effects on 5-HT receptors may act in a synergistic manner on NMDA and GABA currents to potentiate antipsychotic actions in the PFC.
前额叶皮质（PFC）活动减弱与精神分裂症中观察到的许多认知缺陷有关。据推测，用于治疗精神分裂症的抗精神病药物（APD）通过拮抗多巴胺（DA）D2受体来恢复正常活动，而D2受体也已知可调节PFC中的关键离子电流。然而，皮质DA系统活性不足导致精神分裂症症状的假说受到了以下证据的挑战：新型非典型APD是D2受体的弱拮抗剂，但却是5-羟色胺（5-HT）2A受体的强效拮抗剂。本综述探讨了DA和5-HT如何调节皮质活动，以及它们可能以与精神分裂症相关的方式相互作用。得出的结论是，虽然D2受体拮抗作用仍然是恢复受损皮质活动的关键因素，但对5-HT受体的作用可能以协同方式作用于NMDA和GABA电流，以增强PFC中的抗精神病作用。
