November 22, 2016

A Quick Recovery

A drug commonly used for ADHD seems to make recovering from anesthesia much easier.

People have been waking up after surgery in the same way for nearly 200 years — slowly. The anesthetic they were given gradually wears off and, eventually, consciousness returns. That may be about to change.

Considering how long general anesthetics have been used as a surgical tool, very little is known about how they work and especially how people recover from them.

Can this speeded-up arousal lessen anesthesia's undesirable side effects — the grogginess and lingering sense that the brain isn't working as well as it was before the anesthetic was given?

Clues began to emerge when a team of researchers from MIT and Massachusetts General Hospital made the discovery that giving rats Ritalin cut recovery time from one anesthetic (isoflurane) by more than two-thirds.

At first, the researchers weren't even clear on how Ritalin helped rodents wake faster. So they set out to find out.

Since Ritalin is known to increase levels of the neurotransmitter dopamine, that seemed like a good place to start looking. Initial experiments with mice pointed to dopamine-releasing nerve cells in a portion of the brain called the ventral tegmental area (VTA), part of the midbrain.

By engineering nerve cells in that part of the brain to become light sensitive (optogenetics), they were then able to selectively activate them by shining blue laser light at the nerve cells. This allowed the researchers to demonstrate that a small group of dopamine-releasing nerve cells was responsible for early arousal from anesthesia.

Mice were given a dose of isoflurane until they were unconscious and were then placed on their backs. Lying on its back is a sure sign that a mouse is unconscious. Even while asleep, its righting reflex would cause it to flip over onto its front side to make it less vulnerable to predators.

The researchers then activated the modified nerve cells with light, causing them to release dopamine. This caused the mice to immediately wake up and flip over and many to start walking around.

Dopamine has been long known to play an important role in reward, motivation and drug addiction. But it hasn't previously drawn much attention from sleep or consciousness researchers.

Further studies are underway to examine whether this speeded-up arousal also lessens anesthesia's undesirable side effects — the grogginess and lingering sense that the brain isn't working as well as it was before the anesthetic was given, a problem often seen in older patients.

Could this work in people? Trials are underway So far this has only been done with mice and rats, but the results have been (warning: pun coming) eye opening.

The study appears in PNAS, the Proceedings of the National Academy of Sciences.

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