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A retired accountant developed a tremor and slowing of movements and was diagnosed with Parkinson's disease at age 67. At that time, his neurologist prescribed levodopa to restore dopamine levels. Two years later, motor symptoms start to fluctuate and the dopamine receptor agonist ropinirole is added to his treatment.* A few months later, he developed a strong interest in gambling, first buying lottery tickets and then visiting a casino almost every day. He concealed his gambling activity until he had lost more than $100,000. When he came for a consultation 5 weeks ago, ropinirole was replaced with monoamine oxidase inhibitor therapy. He now reports that his interest in gambling has disappeared. Is there a link between the dopamine agonist treatment and gambling addiction?

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*The treatment of Parkinson's disease is discussed in Chapter 28.

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Drugs are abused (used in ways that are not medically approved) because they cause strong feelings of euphoria or alter perception. However, repetitive exposure induces widespread adaptive changes in the brain. As a consequence, drug use may become compulsive—the hallmark of addiction.

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Dependence versus Addiction

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Recent neurobiologic research has led to the conceptual and mechanistic separation of "dependence" and "addiction." The older term "physical dependence" is now denoted as dependence, whereas "psychological dependence" is more simply called addiction.

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Every addictive drug causes its own characteristic spectrum of acute effects, but all have in common that they induce strong feelings of euphoria and reward. With repetitive exposure, addictive drugs induce adaptive changes such as tolerance (ie, escalation of dose to maintain effect). Once the abused drug is no longer available, signs of withdrawal become apparent. A combination of such signs, referred to as the withdrawal syndrome, defines dependence. Dependence is not always a correlate of drug abuse—it can also occur with many classes of nonpsychoactive drugs, eg, sympathomimetic vasoconstrictors and bronchodilators, and organic nitrate vasodilators. Addiction, on the other hand, consists of compulsive, relapsing drug use despite negative consequences, at times triggered by cravings that occur in response to contextual cues (see section: Animal Models in Addiction Research). Although dependence invariably occurs with chronic exposure, only a small percentage of subjects develop a habit, lose control, and become addicted. For example, very few patients who receive opioids as analgesics desire the drug after withdrawal. And only one person out of six becomes addicted within 10 years of first use of cocaine. Conversely, relapse is very common in addicts after a successful withdrawal when, by definition, they are no longer dependent.

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Animal Models in Addiction Research

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Many of the recent advances in addiction research have been made possible by the use of animal models. Since drugs of abuse are not only rewarding but also reinforcing, an animal will learn a behavior (eg, press a lever) when paired with drug administration. In such a self-administration paradigm, the ...

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