Repeated administration of ketamine may lead to neuronal degeneration in the developing rat brain

Background : This study was conducted to investigate, in vivo , the dose and duration effects of ketamine administration on neuronal degeneration in the developing rat brain. Methods : Seven-day-old (P7) Sprague-Dawley rats were treated with intraperitoneal injections of ketamine, a noncompetitive N -methyl-D-aspartate receptor antagonist. Degenerating neurones were identified by the cupric-silver stain from 10 brain regions using the stereological disector method. Results : A single dose of ketamine (25, 50 and 75 mg.kg(-1) ) did not increase neuronal degeneration compared with the saline-treated control. However, repeated doses of ketamine (25 mg.kg(-1) ) at 90-min intervals over 9 h increased degenerating neurones in seven out of 10 brain regions. Conclusions : These findings suggest that the duration of ketamine exposure correlates with increased neuronal degeneration in the developing rat brain.