Unformatted text preview: BASICS A Molecule of Motivation, Dopamine Excels at Its Task By NATALIE ANGIER Published: October 26, 2009 New York Times If you’ve ever had a problem with rodents and woken up to find that mice had chewed their way through the Cheerios, the Famous Amos, three packages of Ramen noodles, and even that carton of baker’s yeast you had bought in a fit of “Ladies of the Canyon” wistfulness, you will appreciate just how freakish is the strain of laboratory mouse that lacks all motivation to eat. Serge Bloch The mouse is physically capable of eating. It still likes the taste of food. Put a kibble in its mouth, and it will chew and swallow, all the while wriggling its nose in apparent rodent satisfaction. Yet left on its own, the mouse will not rouse itself for dinner. The mere thought of walking across the cage and lifting food pellets from the bowl fills it with overwhelming apathy. What is the point, really, of all this ingesting and excreting? Why bother? Days pass, the mouse doesn’t eat, it hardly moves, and within a couple of weeks, it has starved itself to death. Behind the rodent’s fatal case of ennui is a severe deficit of dopamine, one of the essential signaling molecules in the brain. Dopamine has lately become quite fashionable, today’s “it” neurotransmitter, just as serotonin was “it” in the Prozac‐laced ’90s. People talk of getting their “dopamine rush” from chocolate, music, the stock market, the BlackBerry buzz on the thigh — anything that imparts a small, pleasurable thrill. Familiar agents of vice like cocaine, methamphetamine, alcohol and nicotine are known to stimulate the brain’s dopamine circuits, as do increasingly popular stimulants like Adderall and Ritalin. In the communal imagination, dopamine is about rewards, and feeling good, and wanting to feel good again, and if you don’t watch out, you’ll be hooked, a slave to the pleasure lines cruising through your brain. Hey, why do you think they call it dopamine? Yet as new research on dopamine‐deficient mice and other studies reveal, the image of dopamine as our little Bacchus in the brain is misleading, just as was the previous caricature of serotonin as a neural happy face. In the emerging view, discussed in part at the Society for Neuroscience meeting last week in Chicago, dopamine is less about pleasure and reward than about drive and motivation, about figuring out what you have to do to survive and then doing it. “When you can’t breathe, and you’re gasping for air, would you call that pleasurable?” said Nora D. Volkow, a dopamine researcher and director of the National Institute on Drug Abuse. “Or when you’re so hungry that you eat something disgusting, is that pleasurable?” In both responses, Dr. Volkow said, the gasping for oxygen and the wolfing down of something you would ordinarily spurn, the dopamine pathways of the brain are at full throttle. “The whole brain is of one mindset,” she said. “The intense drive to get you out of a state of deprivation and keep you alive.” Dopamine is also part of the brain’s salience filter, its get‐a‐load‐of‐this device. “You can’t pay attention to everything, but you want to be adept as an organism at recognizing things that are novel,” Dr. Volkow said. “You might not notice a fly in the room, but if that fly was fluorescent, your dopamine cells would fire.” In addition, our dopamine‐driven salience detector will focus on familiar objects that we have imbued with high value, both positive and negative: objects we want and objects we fear. If we love chocolate, our dopamine neurons will most likely start to fire at the sight of a pert little chocolate bean lying on the counter. But if we fear cockroaches, those same neurons may fire even harder when we notice that the “bean” has six legs. The pleasurable taste of chocolate per se, however, or the anxiety of cockroach phobia, may well be the handiwork of other signaling molecules, like opiates or stress hormones. Dopamine simply makes a relevant object almost impossible to ignore. Should the brain want to ignore what it might otherwise notice, dopamine must be muzzled. Reporting recently in Nature Neuroscience, Regina M. Sullivan of New York University Medical Center, Gordon A. Barr of Children’s Hospital of Philadelphia and their colleagues found that, whereas rats older than 12 days would quickly develop an aversion to any odors that were paired with a mild electric shock, young rats would perversely show a preference for such odors if their mothers were nearby when the tutorial jolt was delivered. The researchers traced that infantile Candide spirit to a suppression of dopamine activity in the amygdala, where fear memories are born. Infant rats know their mother by smell, Dr. Sullivan explained, and they must not learn to avoid her, for even an abusive caretaker is better than none. Large as its impact may be, dopamine is a compact molecule, built of 22 atoms, with the characteristic nitrogenous amine knob at one end. (Dopamine, by the way, takes its name from its chemical composition, and has nothing to do with the word dope — as in heroin or other recreational drugs — which is thought to derive from the Dutch term for stew.) The dopamine production corps is tiny as well. Fewer than 1 percent of all neurons generate the neurotransmitter, most of them in midbrain structures like the substantia nigra, which helps control movement; it is the degradation of this population of dopamine cells that results in the tremors and other symptoms of Parkinson’s disease. There is also dopamine activity higher up, in the prefrontal cortex parked right behind the forehead, that great executive brain where storylines are written, impulses controlled and excuses contrived. An impoverishment of prefrontal dopamine is thought to contribute to schizophrenia. Wherever their station, brain cells respond to the release of dopamine through one or more of five distinct dopamine receptors poking up from their surface, proteins designed to lock onto dopamine and respond accordingly. Another key player is the dopamine transporter, a kind of janitor that picks up used dopamine molecules and sweeps them back into the cells where they were born. Recreational drugs like cocaine tend to block that transporter, allowing dopamine to linger in the neuronal vestibule and keep punching its signal along. People differ from one another at every juncture of the dopamine matrix, in the tonal background pace at which their dopamine neurons rhythmically fire, the avidity with which the cells spike in response to need or news, and the ease with which hyperstimulated cells revert to baseline. Some researchers have looked at genetic variations in receptor types for clues to personality differences. According to Dan T. A. Eisenberg of Northwestern University, scientists have detected a modest connection between a relatively elongated version of dopamine receptor No. 4 and a tendency toward impulsivity and risk‐taking behavior, particularly financial risk‐taking. One can’t make too much of these preliminary correlations in behavioral genetics, but maybe before the next bailout, we should demand that bankers be tested for the presence of risky, long‐form receptors. It’s the economy, dopamine. ...
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