The Addicted Brain Read Online Free PDF

bar. More details about this kind of experiment are given in subsequent chapters. (Summarized from Jaworski et al.. “Injection of CART Peptide into the Nucleus Accumbens Reduces Cocaine Self-Administration in Rats.”
Behavioral Brain Res
191:266-271, 2008.)

    The bottom line of the story is that CART peptide injected into the brain can function to make cocaine less attractive. Perhaps CART peptide is part of a chemical reflex that tries to control the excess brain activity produced by cocaine, and more will be said about this in later chapters. But, wouldn’t it be interesting if medications based on CART peptide could be developed to make cocaine less attractive to addicts? This last question is speculative because we need to learn much more about CART peptide before we think about treating humans, but you get the idea. There are many experiments like this using drug self-administration that generate many new ideas for additional treatments.
    You can see how important this drug self-administration model is (and other models, too). By showing that drug addiction is a physiological process based in the brain, we can then search for new medications and treatments for addiction that block or reverse the drug-induced processes in the brain. It provides a rational and physiology-based search for new treatments. We can inject drugs directly into various brain regions or surgically alter those regions to define the parts of the brain that mediate addiction. Of course, it goes without saying, that experiments like this using human beings are grossly unethical and impossible. 4 Thus, the animal models make significant progress possible.
Relapse, Craving, and Reinstatement
    Drug abuse is a relapsing disorder. In fact, most drug abusers and addicts have stopped or tried to stop taking drugs, only to eventually relapse. So at any given time, most drug abusers are in fact relapsers. Therefore, it is important to study relapse itself, and this is nicely done in a variant of the self-administration model, as mentioned previously. It works by allowing the animal to learn to self-administer a drug, such as cocaine, until the lever pressing is stable. Then, the drug is withdrawn, and, as expected, the animal gradually tires of lever pressing without a reward and the lever pressing behavior is extinguished. This animal is now an experienced drug user, much like most humans who have used drugs but have stopped. A human in this condition likely thinks about the drug, and when stressed or reminded of the drug, perhaps by some cue, craves the drug and perhaps starts looking for a drug. The cue can be the sight of friends who use drugs, the crack house, or even some white powder that reminds him or her of the drug. Cues and their effects are very interesting and currently studied. For example, Drs. Leslie Lundahl and Chris-Ellyn Johanson recently found that drug-related cues set off cravings in marijuana-dependent subjects. 5 Getting even a small amount of the drug (which is a cue) might set off a binge of drug taking. So, as you can see, certain events can trigger craving, drug seeking, and relapse.
    Now, let’s return to the animal that has experienced a drug but is currently without it. If stress, such as a foot shock, is present or if the drug is injected, the animal remarkably starts to press the lever that previously resulted in a drug injection. The animal does this even if
no drug is given
by the lever press (see Figure 2-4 ). Previous drug use has conditioned the animal to look for the drug in situations that elicit cravings in humans.
    Figure 2-4. Drug self-administration in animals provides a model for relapse in humans. Animals were presented with both a drug-related lever (darker dots) and a nondrug lever (lighter dots). The nondrug lever was rarely pressed as expected (shown on the vertical axis as “responses”). They were trained for 12 days to self-administer cocaine (left half of figure), and drug delivery was accompanied by