Page "Olney's lesions" Paragraph 1

In 1989, Olney et al.

discovered that neuronal vacuolation and other cytotoxic changes (" lesions ") occurred in brains of rats administered NMDA antagonists, including PCP, MK-801 ( dizocilpine ) and ketamine.

Examination of neurons in the posterior cingulate and retrosplenial cortices by electron micrograph revealed apparent lytic breakdown of mitochondria in the large vacuoles which had become apparent 2 hours after administration of an NMDA antagonist.

After administration of 1. 0 ( mg / kg sc ) MK-801 to rats, these neurotoxic changes became more apparent until about 12 hours post-dose, but the morphology of most cells appeared normal by light microscope about 24 hours post-dose.

With 10 ( mg / kg sc ) doses of MK-801, the vacuolation reaction was still visible by light microscope 48 hours post-dose.

After repeated doses of the NMDA antagonists MK-801 and PCP, the vacuolation reaction appeared consistent with the reaction after a single dose, so there was no evidence of a cumulative neurotoxic effect or that the reaction proceeded to an irreversible stage with repeated doses.

The lowest doses of ketamine and tiletamine that produced neurotoxic changes visible by light microscope 4 hours post dose were 40 ( mg / kg sc ) and 10 ( mg / kg sc ), respectively.

The potency of the drugs in producing these neurotoxic changes corresponded with their potency as NMDA antagonists: i. e. MK-801 > PCP > tiletamine > ketamine.