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Addiction's Path

Cocaine. Heroin. The nicotine in cigarettes. They are only a few of the drugs that lead to abuse and addiction. All are known to exert their actions through the brain. Researchers now are identifying common links to several drug addictions, centering around a brain circuit that naturally rewards us for performing activities that keep us alive. Researchers are uncovering the mechanisms that drugs alter in this set of structures. The studies are leading to new treatments for addiction.

      No cereal. No crackers. Even the hidden stash of "M&M's" is depleted. Exasperated, you search the back of your bare cupboards and finally locate the ingredients for a peanut butter and marshmallow fluff sandwich. What is at the root of your urge? A main part of the answer lies in the brain's reward system. This network of neurons, or nerve cells, is activated when we perform functions that help us stay alive, such as eating. It provides a reward and associated pleasurable feelings, which lead us to repeat the activity.
      Researchers have found, however, that most abused drugs also stimulate this system and can induce even greater feelings of pleasure than natural functions. In turn, the drug's influence on the reward circuit can lead a user to bypass survival activities and repeat drug use. Chronic drug use can lead to a powerful cycle of addiction, and in some cases damage the brain and other organs. An addict loses control of drug taking, even when faced with adverse consequences.
      New research shows that this specific brain system underlies addiction to drugs such as cocaine, speed, angel dust, heroin, morphine, alcohol and even the nicotine in tobacco.

The research is leading to:

• A clearer understanding of the biochemical reactions that are common to different drug addictions.
• The development of more effective treatments for addiction.
• Insight on how reminders of drug use set off strong activity in parts of the reward system that appear to be related to craving.

      In the 1950s researchers discovered that rats under some circumstances would dismiss the pleasures of water, food, and sexual partners, to keep an area of the brain over-stimulated by an electrode. The region was dubbed the "reward center." The center blossomed into a circuit when researchers found that a number of linked brain locations are involved in pleasure. Animal studies showed that the structures are powerfully activated by many drugs. The circuit includes a set of neurons found in the ventral tegmental area (VTA), which connect to the nucleus accumbens, and to other areas such as the prefrontal cortex.
      Recent human imaging studies also provide evidence that specific parts of the brain underlie some aspects of addiction. In one study, researchers found that a video, which reminded a user of cocaine, triggered a craving for the drug. This was marked by an increase of activity in parts of the reward system.
      Many neuroscientists now are dissecting the molecular mechanisms that drugs alter in the circuit. The way the chemical messenger dopamine is produced, how its message is received, and how it is inactivated, all appear to be changed by drugs. Researchers believe that a drug's influence on these dopamine mechanisms eventually changes the way the neurons in the system work.
      In rats, the chronic administration of morphine produces a dramatic decrease in the size of neurons that communicate with dopamine in the VTA. Other neurons remain the same size. This implies that drugs can selectively harm circuit cells.
      Some scientists are testing ways to protect the neurons from this drug-induced change. The natural protective molecules called nerve growth factors can reverse the damage to the dopamine neurons in rats. Unfortunately the molecules can't pass into the brain from the blood and must be injected through a hole in the skull. Researchers are searching for ways to set off nerve growth factor activity in the brain with smaller molecules that can navigate their way inside.
      Scientists also are developing methods to block abused drugs from working. Cocaine, for example, activates the system by blocking a pump or transporter that regulates dopamine's signaling. New drugs may attach to the transporter and make it ignore cocaine, but continue its proper function. Other methods target the areas on neurons that receive dopamine, called receptors. The blocking of one type of dopamine receptor appears to stop craving in rats. The treatment now is being tested in humans.
      Future therapies will most likely involve drugs that home in on the reward system, compounds that target reactions specific to a certain drug and behavioral techniques.

Chronic administration of morphine in rats shrinks dopamine neurons in the reward circuit. The receiving branches, called dendrites, wither and the filaments that transport important substances down the neuron's axon are reduced. Nerve growth factors appear to reverse the damage.

Illustration by Lydia Kibiuk, Copyright © 1997 Lydia Kibiuk.