Cocaine and ministrokes

Nov 07 2012 Published by under Behavioral Neuro

We all know that abuse of cocaine results in some pretty severe effects. Usually we think about addiction. When we think about the acute (immediate) effects of cocaine, we think of things like increased heart rate and blood pressure, and the possibility of heart attack from an overdose. But maybe we should also think about strokes. Ministrokes. In the brain.

"Cocaine-induced cortical microischemia in the rodent brain: clinical implications" Molecular Psychiatry, 2012.

Why should we think of heart attack or stroke? Because cocaine, aside from being a drug that inhibits the recycling of dopamine and produces a feeling of 'high', is also a potent vasoconstrictor, meaning that it causes your blood vessels to narrow. This is usually due to increased blood pressure from the inhibition of dopamine and norepinephrine recycling, the more dopamine and norepinephrine there is around, the more vasoconstriction results. At high doses, this means that cocaine can cause life threatening strokes (actually a bigger cause of death in young adults taking cocaine than heart attacks). But even at normal doses, cocaine produces some pretty significant increases in blood pressure.

And increases in blood pressure and vasoconstriction mean that you get restrictions in blood flow. And this is especially interesting in the brain, where restrictions of blood flow for long enough can result in the death of your neurons. But it's been hard to tell just how MUCH vasoconstriction and restriction of cerebral blood flow is going on. Much of this is thought to take place at the level of capillaries so small that they could not be distinguished by imaging.

Until now. And the results are both scientifically interesting, and eerily beautiful.

The authors of this study took high resolution Doppler optical coherence tomography (which allows you to image structures at micrometers of scale), and used an algorithm to image blood flow within capillaries as well as the capillaries themselves, which allowed them to put together a 3D map of blood vessels in the brain.)

When they had this incredibly complicated technique working in the mouse brain, they then injected the mice with a single dose, or multiple doses of cocaine.

The figure above shows a single dose of i.v. cocaine. If you look carefully at the green arrows, you will see the disappearance of a small arteriole (the smaller version of an artery) from the image. This is not due to it going away in the brain. Instead, the image is lost because there is such a restriction of blood flow through that vessel that it cannot be tracked. This was especially apparently in the arteries, where 77% showed a response to a single dose of cocaine, while only 23% of veins did.

And it got worse when the doses were repeated.

Here you can see the effects of three acute doses of cocaine. The effect was stronger after repeated cocaine. Luckily the restriction recovers faster in arteries (within 5 minutes) than it does in veins (within 12 minutes), but some arteries showed effects up to 45 minutes later.

This restriction of blood flow at such a small level could end up having big effects. The fact that it gets worse with repeated cocaine dosing could mean that repeated cocaine users (who use more than once in a night, for example) are at risk for tiny microstrokes in the brain, and this could contribute to the neuronal death that is often seen in cocaine abusers. It's an interesting study into the mechanisms of cocaine, but it also shows how beautiful the working body can be.

Ren H, Du C, Yuan Z, Park K, Volkow ND, & Pan Y (2012). Cocaine-induced cortical microischemia in the rodent brain: clinical implications. Molecular psychiatry, 17 (10), 1017-25 PMID: 22124273

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