Novella on Glutamine, AMPA and Antidepressants

The comment-posting mechanism over at NeuroLogica seems to be on the fritz, so I’ll take this opportunity to use my own blag to thank Dr. Steven Novella for replying to my question about a new potential class of antidepressants. I had noticed a glancing mention of neuroscientists growing interested in treating depression by working on the brain’s glutamate mechanisms.

The short version is that ketamine, an anaesthetic, veterinary tranquilizer and sometimes recreational drug, mucks with the brain’s neurotransmitter signaling by blocking NMDA receptors, thereby leaving more glutamate floating in the synapses to bind to AMPA receptors. And, in not-very-rigorous trials, this seems to make people happier!

Clearly, the next logical step is to start giving drugs to laboratory animals. C. A. Zarate and colleagues at NIMH found that doping mice with a drug which inhibited AMPA receptors reduced the behavioral effects of ketamine. This suggests that compounds which work directly to boost AMPA receptor activity — AMPA agonists — might also have an antidepressant effect.

All in all, fascinating stuff.