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| Archive : Fall
2006 |
BEEN DOWN SO LONG IT LOOKS LIKE UP TO ME:
First dopamine whisks you into euphoria // Then compulsion displaces pleasure // Eventually, just the sight of a $20 bill makes your brain scream cocaine // Now, is there any way to replace the brain tissue
that got eaten away?
The Addicted Brain [page 3]
 By Anita Slomski
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Dopamine is very much involved in how this circuit learns and adapts, but once the infrastructure of the circuit gets changed through drug use, it’s really GABA and glutamate that drive drug-seeking behavior,” says Peter Kalivas, professor and chair of the department of neurosciences at the Medical University of South Carolina at Charleston.
That’s why, instead of targeting dopamine, some researchers are testing what happens when GABA transmission is enhanced with anticonvulsants or muscle relaxants, or the production of glutamate is inhibited. The trick is to get a therapeutic effect without causing lethargy, cognitive slowing or loss of motivation. Kalivas is encouraged by the results of experiments with rats and a promising Phase I human study with cocaine addicts in which an antioxidant compound, N-acetylcysteine, inhibited cravings for cocaine and dampened activity in addicts’ prefrontal cortices—home to glutamate and GABA activity—when the addicts were shown drug cues. “Our guess is that this won’t be a cure but that it will help restore some cognitive function,” says Kalivas, “though it may not help the hard-core addict who is extremely cognitively impaired.”
Yet another approach may be to amplify the dopamine response to non-drug-related stimuli, assuming researchers can find the right dopamine receptors to target. “If you can increase drug abusers’ sensitivity to natural reinforcers like sex and food, then they have alternative behaviors to help them feel good,” says Volkow.
Even as they crave the rush of their next hit, some addicts realize there’s a cost to getting high. That’s the executive brain talking—specifically, the anterior cingulate. But the executive brain, associated with decision-making and judgment, gradually loses sway as addiction takes hold. “The end stage of drug abuse is the disconnection—functionally or even structurally—of the primitive limbic brain from the more developed frontal cortical brain,” explains psychiatrist and neurologist Walter Ling, director of the Integrated Substance Abuse Programs at the University of California at Los Angeles.
To test the breakdown of the brain’s executive function, NIDA’s Stein compared brain images of cocaine addicts with those of a control group as the subjects pressed a button to identify patterns in a rapidly changing sequence of letters. When a subject made a mistake, the anterior cingulate, which monitors and recognizes errors, did not light up on the scan nearly as brightly among cocaine users as it did among members of the control group. “The ability of the cocaine addict’s brain to recognize an error was severely impeded,” says Stein. “Just saying no to drugs clearly doesn’t work for addicts because their brains are significantly impaired in coping with the conflict that arises when the no signal meets the yes signal brought on by a drug cue.”
But when the addicts were high on cocaine during this experiment, the rush of dopamine allowed their usually sluggish cingulates to approach normal levels. That suggests that a drug that increases dopamine might enhance compromised dopamine levels in the anterior cingulate and other areas and perhaps restore some of the dysfunctional dopamine circuitry. Stein also thinks that the brain’s cognitive circuitry can be bolstered by the rehabilitation of the anterior cingulate in the same way that therapy helps stroke victims relearn how to speak and move. “If we think of the anterior cingulate as a muscle that has atrophied, maybe we can use biofeedback to give people information about their cingulate activity and ask them to try to increase it, much as we might give feedback on muscle performance,” says Stein, who is writing a protocol for a clinical trial to test his idea. |
Next page | Pages: 1 2 3 4
Photographs by James Worrell |
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