Neural Changes With Chronic Drug

Both withdrawal and the pleasant or euphoric effects from drug use occur, in part, as a result of the drug's action on the brain. The immediate or acute effects of most drugs of abuse affect areas of the brain that have been associated with ''reward'' or pleasure. These drugs stimulate areas normally aroused by natural pleasures such as eating or sexual activity. Long-term, or chronic, drug use alters these and other brain areas. Some brain areas will develop TOLERANCE to the drug effects, so that greater and greater amounts are needed to achieve the original effects of the drug. Some examples of drug effects that develop tolerance are the ANALGESIC or painkilling effect of opiates and the euphoria-or pleasure-producing effect of most drugs of abuse, which are probably related to their abuse potential.

Because some brain areas may also become sensitized, an original drug effect will either require a lesser amount of the drug to elicit the effect when the drug is used chronically or the effect becomes greater with chronic use. This phenomenon has been studied most extensively in cocaine use. Cocaine is associated with behavioral sensitization of motor activity in animals and paranoia (extreme delusional fear) in humans. There are physiological effects that develop tolerance or sensitization as well. For example, the chronic use of cocaine will sensitize some brain areas so that seizures are more easily induced. Other health risks of drug use will be addressed below.

In addition to these more direct acute and chronic drug effects, another phenomenon occurs with long-term drug use. This phenomenon is the conditioned drug effect, in which the environmental or internal (mood states) cues commonly presented with drug use become conditioned or psychologically associated with drug use. For example, when angry, a drug addict may buy or use drugs in a certain place with certain people. After frequently taking drugs under similar conditions, the individual can experience a strong craving or even withdrawal when in the environment in which he or she has taken drugs or feels angry. When the individual tries to stop using drugs, exposure to these conditioned cues can often lead to relapse because the craving and withdrawal effects are so powerful. Very little research has been done on the neural bases of these conditioned effects; thus it is not known whether these effects are mediated by similar or different neural mechanisms.

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