Dopamine is the key chemical player in drug addiction. Excesses (and shortages) of this pleasure-inducing hormone feed the cycle of enhanced sensations and subsequent cravings that define chemical dependence. Researchers at the renowned Brookhaven National Laboratory now believe that they can mitigate the addiction cycle by artificially leveling the amount of dopamine and the receptor genes that activate it within the affected brain. In the latest study on this subject, rats who'd been conditioned toward an addiction to self-administered cocaine responded positively to gene therapy treatment, with their interest in the drug waning considerably.
Any sense of physical pleasure we feel - whether caused by good food, intense exercise, or intoxicaton - stems from the release of the neurochemical dopamine and its subsequent absorption by dopamine receptor proteins in the brain. In order to provide their respective highs, alcohol and other drugs prompt the brain to release abnormally large quantities of the hormone, and this overactivity swamps the receptors and renders them less effective with time. The "blunted" sensation experienced by many addicts who truly cannot experience pleasure without their drug of choice comes from this extended dopamine imbalance. In keeping with this model, researchers believe that individuals with low dopamine receptor (D2) levels are particularly susceptible to addiction. Flooding an addicted brain with dopamine may seem like a counterintuitive strategy, but it makes sense in this context as it works to restore the brain's ability to experience pleasure without the influence of the drug in question.
The rats in this study had been provided with self-administered cocaine for 2 weeks, a period long enough to facilitate addiction. Using a lever, the rats dosed themselves with the drug at their own discretion. As predicted, they became dependent on the drug, their quantities of usage increasing. In order to facilitate the development of replacement D2 receptors in the rat's brains, researchers injected their brains with a benign virus that had been modified to carry a D2 receptor gene. After receiving this injection, the rats' brains began producing more of the receptor proteins on their own, thereby eliminating the gap between the amount of dopamine present and the number of receptors available to receive it. Affected rats then considerably reduced their cocaine consumption rates. They used 75% less of the drug for a period lasting approximately 6 days (at which time the balance brought about by the receptor gene presumably wore off and their drug use returned to its previous levels).
Previous studies by the same lab came to similar conclusions regarding alcohol dependence, finding that the act of introducing excess dopamine into the brains of addicted lab rats led them away from their cravings and normalized their pleasure responses. By artificially boosting the number of available receptors and allowing the rats' brains to fully process all the dopamine in their systems, researchers essentially fooled them into believing that their pleasure urges had already been satisfied, all but eliminating their physiological need for the drug. The fact that the same procedures produced identical results when alcohol was the variable also implies that different types of addictive drugs, all of which work through the release of dopamine, will respond in the same way. If this pattern holds true, the potential applications of their research are extremely significant. The concept of injecting a modified viral compound directly into the brains of human subjects is not currently viable, but alternate methods of gene therapy will certainly be developed. At the very least, these studies have helped us better understand the mechanisms of addiction and improved our ability to predict its phases. Human treatments seem inevitable.
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