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

• Published in: Pediatric anesthesia 2002-11, Vol.12 (9), p.770-774
• Main Authors: HAYASHI, HIDEAKI, DIKKES, PIETER, SORIANO, SULPICIO G.
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; apoptosis; Biological and medical sciences; Brain - drug effects; Brain - growth & development; Drug toxicity and drugs side effects treatment; Ketamine - administration & dosage; Ketamine - pharmacology; ketamine neonate; Medical sciences; N-methyl-D-aspartate; Nerve Degeneration - chemically induced; neuronal degeneration; neurotoxicity; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Time Factors; Toxicity: nervous system and muscle
• ISSN: 1155-5645; 1460-9592
• DOI: 10.1046/j.1460-9592.2002.00883.x

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.