Olney's lesions

Olney's lesions, also known as NMDA receptor antagonist neurotoxicity (NAT), is a form of brain damage consisting of selective death of neurons but not glia, observed in restricted brain regions of rats and certain other animal models exposed to large quantities of psychoactive drugs that inhibit the normal operation of the neuronal NMDA receptor.

The visible signs of NAT are named after John Olney, who conducted a study in 1989 to investigate neurotoxicity caused by PCP and related drugs.

In the late 1980s, John Olney, a researcher specializing in excitotoxicity, the phenomenon where persistently high neurotransmitter concentrations damage nerve cells, began to investigate the pharmacology of NMDA receptor antagonists.

Other workers had recently begun proposing to use NMDA antagonists PCP, MK-801 (dizocilpine) and ketamine in clinical trials for various psychological effects; but the drugs' current illegality meant that scientists had no record of pharmacological response to guide safe use.

The regions of the brain that show neuronal death are remarkably restricted, and consist chiefly of the cingulate and retrosplenial cortex.

[4] Varying the dosing regimes revealed that the drugs' lesiary potency correlated with their NMDA antagonism (MK-801 > PCP > tiletamine > ketamine).

[5] Researcher Roland N. Auer conducted similar studies to look at the correlation between age and sex and the development of NMDA receptor antagonist neurotoxicity in test rats.

[6] Dextromethorphan, a common antitussive often found in cough medicines, has been shown to cause vacuolization in rats' brains when administered at doses of 75 mg/(kg ip).

[11][12] In Ketamine: Dreams and Realities, Karl Jansen writes: Roland Auer injected the common squirrel monkey with Dizocilpine, or MK-801 and was unable to produce any vacuoles.