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Dr. Antonello Bonci

June 27, 2014

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We replicated, so to speak, a compulsive model in rodents that had a very negative component.

And basically, these rats would self-administer cocaine despite a negative consequence, which in this case was a mild foot shock.

First of all, we learned this amazing finding that the brain area which is called the prelimbic portion of the prefrontal cortex in these rats was hypoactive—less active than normal.

And this brain area is the equivalent of a brain region in humans in the frontal cortical part of our brain which is also very hypoactive in humans after chronic cocaine exposure.

So this is a brain region that actually controls our ability to make decisions, our ability to understand that an action can have a positive or a negative consequence, and basically these compulsive cocaine seekers had, like in humans, very low activity of this portion of the frontal cortex.

We have this amazing technique which was discovered just a few years ago at Stanford called optogenetics, so sounds like science fiction, but basically with this technique, we can use a virus and we can inject this virus into this hypoactive part of the rodent’s brain called the prefrontal cortex.

And by injecting this virus, we can deliver with a laser light a signal, a wavelength of light that will turn on this hypoactive portion of the rodent’s brain.

And basically when we did that, this compulsive cocaine seeking immediately disappeared.

Despite having these rats been exposed for months to cocaine seeking, and despite going through foot shocks and still wanting to seek and take cocaine, the moment we turned on this activity, via this light, of the prefrontal cortex, this compulsive cocaine seeking immediately disappeared.

So this is a very astonishing finding for us.

What this means for people is that we can translate these findings in several different ways.

First of all, we have a brain region that is a target.

We know it is hypoactive, as we knew through human studies, but we also know for the first time that turning on—back to normal, if you will—this brain region will wipe out this behavior in rodents.

So there are techniques that are currently used in patients that are used for depression, for Parkinson’s disease, for obsessive-compulsive disorder, and these techniques are called transcranial magnetic stimulation, or TMS, or deep brain stimulation, or DBS.

And they can basically activate classes of brain cells by targeting specific brain regions.

So in this case, instead of having to wait, for example, 15 years to develop a new molecule that goes from basic science to treatment, we can use these currently available and safe techniques to basically design clinical trials with the idea of stimulating precisely this prelimbic portion of the prefrontal cortex of human brains to really try to wipe out symptoms of cocaine addiction.

This page was last updated June 2014

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