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As a test of his model, Montague created a computer program that simulated the nectar-gathering activity of bees. Programmed with a dopamine-like reward system and set loose on a field of virtual "flowers," some of which were dependably sweet and some of which were either very sweet or not sweet at all, the virtual bees chose the reliably sweet flowers 85% of the time. In laboratory experiments real bees behave just like their virtual counterparts. What does this have to do with drug abuse? Possibly quite a lot, says Montague. The theory is that dopamine-enhancing chemicals fool the brain into thinking drugs are as beneficial as nectar to the bee, thus hijacking a natural reward system that dates back millions of years.
The degree to which learning and memory sustain the addictive process is only now being appreciated. Each time a neurotransmitter like dopamine floods a synapse, scientists believe, circuits that trigger thoughts and motivate actions are etched onto the brain. Indeed, the neurochemistry supporting addiction is so powerful that the people, objects and places associated with drug taking are also imprinted on the brain. Stimulated by food, sex or the smell of tobacco, former smokers can no more control the urge to light up than Pavlov's dogs could stop their urge to salivate. For months Rafael Rios lived in fear of catching a glimpse of bare arms his own or someone else's. Whenever he did, he remembers, he would be seized by a nearly unbearable urge to find a drug-filled syringe.
Indeed, the brain has many devious tricks for ensuring that the irrational act of taking drugs, deemed "good" because it enhances dopamine, will be repeated. pet-scan images taken by Volkow and her colleagues reveal that the absorption of a cocaine-like chemical by neurons is profoundly reduced in cocaine addicts in contrast to normal subjects. One explanation: the addicts' neurons, assaulted by abnormally high levels of dopamine, have responded defensively and reduced the number of sites (or receptors) to which dopamine can bind. In the absence of drugs, these nerve cells probably experience a dopamine deficit, Volkow speculates, so while addicts begin by taking drugs to feel high, they end up taking them in order not to feel low.
PET-SCAN images of the brains of recovering cocaine addicts reveal other striking changes, including a dramatically impaired ability to process glucose, the primary energy source for working neurons. Moreover, this impairment which persists for up to 100 days after withdrawal is greatest in the prefrontal cortex, a dopamine-rich area of the brain that controls impulsive and irrational behavior. Addicts, in fact, display many of the symptoms shown by patients who have suffered strokes or injuries to the prefrontal cortex. Damage to this region, University of Iowa neurologist Antonio Damasio and his colleagues have demonstrated, destroys the emotional compass that controls behaviors the patient knows are unacceptable.
Anyone who doubts that genes influence behavior should see the mice in Marc Caron's lab. These tireless rodents race around their cages for hours on end. They lose weight because they rarely stop to eat, and then they drop from exhaustion because they are unable to sleep.
Why? The mice, says Caron, a biochemist at Duke University's Howard Hughes Medical Institute laboratory, are high on dopamine. They lack the genetic mechanism that sponges up this powerful stuff and spirits it away. Result: there is so much dopamine banging around in the poor creatures' synapses that the mice, though drug-free, act as if they were strung out on cocaine.