Stress Intervention

Scientists have discovered a way to shut down the brain’s “stress process” before it gets going, says a new study.

Stress, or just a very acute case of the munchies? It's hard to say.

By blocking the brain’s ability to manufacture certain chemicals called neurosteroids, researchers have managed to temporarily cut off a biological process crucial for stressful behavior – and for many stressful feelings as well.

Animals from amphibians all the way up to humans produce a hormone called corticosterone in their adrenal glands. Corticosterone levels become elevated under stress, and this hormone is a major ingredient in a number of stress-related biological processes, from feelings of nervousness to aggressive behavior.

Corticosterone does most of its direct work within a brain pathway known as the hypothalamic-pituitary-adrenal axis (also called the HPA or HTPA axis). To be honest, the word “pathway” is a bit of an oversimplification – the HPA is actually a whole set of neurochemical feedback circuits involved in regulating digestion, immune response, and mood, among other things.

The HPA’s activity is mostly regulated by a neurotransmitter chemical called gamma-Aminobutyric acid (GABA to its friends). GABA is typically an inhibitory neurotransmitter, which means it prevents electrochemical signals from being passed beyond a certain point. It often works closely with a neurosteroid called tetrahydrodeoxycorticosterone (THDOC), which helps its inhibitory effects spread even more widely throughout the HPA.

But when we come under stress, everything changes: the adrenal glands start cranking out extra-large doses of THDOC and sending them up into the HPA. And here’s where things get weird – those conditions trigger a certain electrochemical shift that causes GABA and THDOC to activate the HPA rather than inhibit it.

As the Journal of Neuroscience reports, the discovery of that neurochemical mechanism is the first half of a two-part breakthrough made Jamie Maguire‘s team at Tufts University:

We have identified a novel mechanism regulating the body’s response to stress by determining that neurosteroids are required to mount the physiological response to stress.

But how did they discover this mechanism, you ask? Well, since the team suspected that neurosteroidogenesis – the production of neurosteroids like THDOC – was a crucial component in stress-related HPA activation, they got a bright idea: they wondered if a drug that blocked neurosteroidogenesis might be able to stop the brain’s stress response before it could even get into gear.

As it turned out, they were right – they cut off the THDOC rush by administering a drug called finasteride – which you might’ve heard of under the brand name Propecia. Yep, the baldness drug:

Blocking neurosteroidogenesis with finasteride is sufficient to block the stress-induced elevations in corticosterone and prevent stress-induced anxiety-like behaviors in mice.

In other words, the researchers found that finasteride does more than just control stress – it blocks the chemical cascade that causes stress-related feelings and behavior. As far as they can tell, it prevents animals from experiencing stress at all - at least temporarily.

This has the potential to develop into a far more powerful treatment than benzodiazepines like Xanax and Ativan, which work by helping GABA inhibit more activity than it normally would. By contrast, a finasteride-like drug would make it almost impossible to feel stressed, even if you tried – meaning this drug might also be used to treat diseases like epilepsy and major depression, which have been linked to excessive activation of the HPA.

Right now, Maguire’s team is focused on isolating more of the exact neural connections that play roles in disorders like these. That means it may be a few years before this “wonder drug” becomes available. In the meantime, I wouldn’t recommend swallowing handfuls of Propecia when you’re feeling stressed – the drug needs to be applied in a pretty targeted way to make this work, which means a major part of pharmaceutical development will be the creation of an effective chemical delivery system.

Even so, it’s exciting to think that before long, depression and anxiety may be as easy to prevent as, say, polio and malaria are today. The thought’s enough to get my hormones pumping, anyway.


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One Response to “Stress Intervention”

  1. […] Remember, it’s not always a bad thing It sometimes helps to remember that stress is a natural phenomenon…as natural as digestion or sleep. Though stress (or sadness, or worry) can sometimes get out […]

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