Beyond the pleasure principle: sure, drugs feel good--but they're addicting because they co-opt memory and motivation systems, not just pleasure pathways. (Addiction: long-term changes)

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Author: Laura Helmuth
Date: Nov. 2, 2001
From: Science(Vol. 294, Issue 5544)
Publisher: American Association for the Advancement of Science
Document Type: Article
Length: 1,904 words

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When it comes to kicking a drug habit, going through withdrawal is the easy part. The cold-turkey alcoholic shaking with delirium tremens might not agree, but only after the body detoxifies does the real challenge begin: staying clean. Ex-addicts with the strongest resolve--and plenty of external motivation in the form of frayed relationships, probationary jobs, or incipient lung cancer--struggle to resist cravings and are susceptible to relapse even years after their last dose.

Researchers have spent decades studying the immediate effects of drugs on the brain. Drugs cause short-term surges in dopamine and other brain messengers that signal pleasure or reward. But the brain quickly adapts to this deluge; pleasure circuits overwhelmed by drugs' signals desensitize--so much so that the brain can suffer withdrawal once the binge is over.

In the past decade or so, many researchers have started to focus on a more daunting problem: the long-term consequences of drug abuse. Many drugs don't induce much pleasure after prolonged use, in part because of desensitization, or tolerance. So why do addicts keep taking their drug of choice, even when they try to abstain? To find out, researchers are seeking clues in parts of the brain that help control motivation, looking for changes that happen after weeks, months, and years of exposure to drugs.

Some of the neural changes they've found look very familiar: Addiction seems to rely on some of the same neurobiological mechanisms that underlie learning and memory, and cravings are triggered by memories and situations associated with drug use. Recent studies have revealed a "convergence between changes caused by drugs of addiction in reward circuits and changes in other brain regions mediating memory," says neuroscientist Eric Nestler of the University of Texas Southwestern Medical Center in Dallas. For instance, both learning and drug exposure resculpt synapses, initiate cascades of molecular signals that turn on genes, and change behavior in persistent ways. Understanding these processes could help addicts conquer relapse, "the core clinical problem" of addiction, says Steven Hyman, director of the National Institute of Mental Health in Bethesda, Maryland (soon to depart for Harvard University; see p. 970). "If we want to focus on the clinical issue that matters, we have to understand how associative memories are laid down that change the emotional value of drugs and create deeply ingrained behavioral responses to those cues [that trigger relapse]."

Memories you remember

Memory researchers divide memories into those you consciously remember and those you generally don't. Consciously, people may remember a past drug-induced burst of euphoria and seek out the drug again, or they may remember that drugs stop them from feeling crummy. This type of memory is "good at explaining why people take drugs, but it doesn't explain addiction," says Terry Robinson of the University of Michigan, Ann Arbor. Plenty of people dabble in drug use for just such pleasure-related reasons, but addiction...

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