The Addicted Brain Read Online Free PDF Page A

extending and examining the model more closely, you can study additional aspects or phases of drug addiction. These include: the initiation of drug taking or the rate at which an animal learns to self-administer it; the maintenance of drug taking, which is the phase where the lever pressing has been learned and is stable or relatively unchanging; the extinction of drug taking, which occurs when the lever pressing no longer produces a drug reward and the lever pressing gradually stops; and the relapse to drug taking, which is either stress, cue (see the following sidebar), or drug-induced, and occurs when an extinguished subject begins to seek drugs again. These four phases are different and can rely on different processes in the brain. Moreover, certain medications can be more effective in treating one phase compared to the other phases. Thus, the tools for searching for medications and treatments are becoming more sophisticated.
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    A “cue,” in this context, is anything that reminds you of drugs or taking drugs. It can be the sight of a friend that you take drugs with, the place where you have taken drugs, or even something like a white powder whether it is drug or not. The importance of a cue is that it can precipitate a relapse. A cue can trigger a response in your brain that makes you want drugs. Someone who wants to stop taking drugs must learn his or her cues, or danger signs, that lead to craving and more drug taking, and he or she must avoid them or neutralize them in his or her mind.
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An Example of a New Idea
    An example of how this model can be used to explore new ideas is an experiment with CART peptide that comes from the author’s laboratory. CART peptide is a chemical found in brain regions that areinvolved in drug abuse, and the effect of CART peptide on drug taking can be explored by using this animal model. If an animal has been allowed to learn the self-administration of cocaine, it can then be forced to give up or extinguish lever pressing by requiring a very large number of lever presses to get a reward. Instead of getting a drug injection for every lever press or for every other lever press, the number of lever presses required to get just one injection of cocaine can be made so great that the animal just gives up pressing. Now, here is the key part. The drugs that the animals like better elicit more attempts to get the drug than other less desirable drugs. The number of presses that the animal makes for a drug before it gives up is a measure of how much the animal wants the drug. Suppose animals are allowed to lever press to get injections of cocaine, and they learn to expect this whenever they press the lever. By withholding the drug injection, the number of presses required before they give up lever pressing can be measured. An interesting experimental result is that if CART peptide is injected into critical brain regions, the animal gives up lever pressing
sooner
( Figure 2-3 ). It appears that the animal is less interested in getting a cocaine reward when it has been given CART peptide.
    Figure 2-3. Injections of CART peptide reduce cocaine reward and intake. Animals work to receive injections of cocaine by lever pressing because they find cocaine rewarding and they want it. In fact, they press the lever many times to get a single injection of the drug. Now let’s add another part to the experiment. If a drug-free solution (aCSF) is injected into the brain, the animals can still press for cocaine hoping to get some drug (the number of presses corresponds to the height of the bars in the figure). But if CART peptide (2.5 micrograms) is injected into a part of the brain associated with cocaine use (the nucleus accumbens), then the animal works much less for cocaine as indicated by the shorter bar on the right. You can think of the length of the bar as a measure of cocaine’s desirability to the animal, and an injection of CART peptide reduces the desirability of cocaine and shortens the