Sharp F R, Butman M, Wang S, Koistinaho J, Graham S H, Sagar S M, Noble L, Berger P, Longo F M
Department of Neurology, University of California, San Francisco.
J Neurosci Res. 1992 Dec;33(4):605-16. doi: 10.1002/jnr.490330413.
The non-competitive NMDA receptor antagonists, PCP (phencyclidine), MK801, and ketamine produce psychosis in humans and abnormal vacuoles in posterior cingulate and retrosplenial rat cortical neurons. We show that PCP (> or = 5 mg/kg), MK801 (> or = 0.1 mg/kg), and ketamine (> 20 mg/kg) induce hsp70 mRNA and HSP70 heat shock protein in these vacuolated, injured neurons, and PCP also induces hsp70 in injured neocortical, piriform, and amygdala neurons. The PCP, MK801, and ketamine drug induced injury occurs in 30 day and older rats, but not in 0-20 day old rats, and is prevented by prior administration of the antipsychotic drugs haloperidol and rimcazole. Since haloperidol and rimcazole block dopamine and sigma receptors, and since M1 muscarinic cholinergic receptor antagonists also prevent the injury produced by PCP, MK801, and ketamine, future studies will be needed to determine whether dopamine, sigma, M1, or other receptors mediate the injury.
非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂苯环己哌啶（PCP）、氯胺酮（MK801）和氯胺酮可导致人类出现精神病症状，并使大鼠后扣带回和压后皮质神经元产生异常空泡。我们发现，PCP（≥5mg/kg）、MK801（≥0.1mg/kg）和氯胺酮（>20mg/kg）可在这些出现空泡的受损神经元中诱导热休克蛋白70（hsp70）信使核糖核酸（mRNA）和热休克蛋白70（HSP70）产生，PCP还可在受损的新皮质、梨状皮质和杏仁核神经元中诱导hsp70产生。PCP、MK801和氯胺酮所致的药物损伤发生在30日龄及以上的大鼠中，而在0至20日龄的大鼠中则不会发生，且预先给予抗精神病药物氟哌啶醇和利咪唑可预防这种损伤。由于氟哌啶醇和利咪唑可阻断多巴胺受体和σ受体，且M1毒蕈碱胆碱能受体拮抗剂也可预防PCP、MK801和氯胺酮所致的损伤，因此未来需要开展研究以确定多巴胺、σ、M1或其他受体是否介导了这种损伤。
