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.