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(used in ways that are not medically approved) because they cause strong feelings of euphoria or alter perception.

Drugs are abused

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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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is now denoted as dependence

"physical dependence

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is more simply called addiction.

psychological dependence

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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 o

euphoria and reward.

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With repetitive exposure, addictive drugs induce adaptive changes such as

tolerance

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escalation of dose to maintain effect).

 tolerance

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Once the abused drug is no longer available, signs of() become apparent.

withdrawal

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A combination of such signs, referred to as the (), defines dependence

withdrawal syndrome

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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

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With chronic exposure to addictive drugs, the brain shows signs of adaptation. For example, if morphine is used at short intervals, the dose has to be progressively increased over the course of several days to maintain rewarding or analgesic effects. o This phenomenon is called

tolerance

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It may become a serious problem because of increasing side effects-eg, respiratory depression-that do not show much tolerance and may lead to fatalities associated with

overdose

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Tolerance to opioids may be due to a () of the concentration of a drug or a () duration of action in a target system (pharmacokinetic tolerance)

reduction , shorter

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s characterized by a high motivation to obtain and use a drug despite negative consequences. With time, drug use becomes compulsive ("wanting without liking").

Addiction

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is a recalcitrant, chronic, and stubbornly relapsing disease that is very difficult to treat.

addiction

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The central problem is that even after successful withdrawal and prolonged drug free periods, addicted individuals have a high risk of

relapsing

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RELAPSE IS TRIGGERED BY ONE OF THE FOLLOWING

. Re-exposure to the addictive drug, stress, or a context that recalls prior drug use. Motivate ("trigger") addictionrelated behavior.

2. The involvement of learning and memory systems in addiction.

. Large individual differences exist also in vulnerability to substance related addiction. Whereas one person may become "hooked" after a few doses, others may be able to use a drug occasionally during their entire lives without ever having difficulty in stopping.

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This phenomenon may involve synaptic plasticity in the target nuclei of the

mesolimbic projection

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Several recent studies suggest that the recruitment of the() is responsible for the compulsion.

dorsal striatum

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For example, the role of context in relapse is supported by the report that soldiers who became addicted to heroin during the Vietnam War had significantly better outcomes when treated after their return home, compared with addicts who remained in the environment where they had taken the drug. In other words, cravings may recur at the presentation of

contextual cues

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