Institute of Biomedicine and Biotechnology of Cantabria, IBBTEC (CSIC-University of Cantabria), Calle Albert Einstein 22 (PCTCAN), 39011 Santander, Spain.
Biomedical Research Networking Center for Mental Health (CIBERSAM), 39011 Santander, Spain.
Biomolecules. 2020 Jun 23;10(6):947. doi: 10.3390/biom10060947.
N-methyl-D-aspartate (NMDA) receptor antagonists such as phencyclidine (PCP), dizocilpine (MK-801) and ketamine have long been considered a model of schizophrenia, both in animals and humans. However, ketamine has been recently approved for treatment-resistant depression, although with severe restrictions. Interestingly, the dosage in both conditions is similar, and positive symptoms of schizophrenia appear before antidepressant effects emerge. Here, we describe the temporal mechanisms implicated in schizophrenia-like and antidepressant-like effects of NMDA blockade in rats, and postulate that such effects may indicate that NMDA receptor antagonists induce similar mechanistic effects, and only the basal pre-drug state of the organism delimitates the overall outcome. Hence, blockade of NMDA receptors in depressive-like status can lead to amelioration or remission of symptoms, whereas healthy individuals develop psychotic symptoms and schizophrenia patients show an exacerbation of these symptoms after the administration of NMDA receptor antagonists.
N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，如苯环利定（PCP）、地佐环平（MK-801）和氯胺酮，长期以来一直被认为是精神分裂症的模型，无论是在动物还是人类中。然而，氯胺酮最近已被批准用于治疗抵抗性抑郁症，尽管有严格的限制。有趣的是，两种情况下的剂量相似，精神分裂症的阳性症状先于抗抑郁作用出现。在这里，我们描述了 NMDA 阻断在大鼠中引起类似精神分裂症和抗抑郁样效应的时间机制，并假设这种效应可能表明 NMDA 受体拮抗剂诱导相似的机制效应，而仅有机体的基础药物前状态限制了整体结果。因此，在抑郁状态下阻断 NMDA 受体可以改善或缓解症状，而健康个体在服用 NMDA 受体拮抗剂后会出现精神病症状，精神分裂症患者会出现这些症状的恶化。
