High Price

accumbens. According to the theory, this center was supposed to be activated by “natural” rewards like sex or food, things that would help an animal compete in the evolutionary race for survival. But drugs can increase the activity of dopamine neurons even more than these ordinary pleasures. As a result, with their brains taken hostage by these unnatural experiences, addicts were seen as inevitably doomed to lose control over their behavior. The need to chase more dopamine would leave them begging, borrowing, stealing, dealing, even killing for more drugs as a result. Dopamine was said to make crack cocaine irresistible and crack addicts’ behavior uncontrollable.
    This “dopamine hypothesis of addiction” had its beginnings in an accidental observation by James Olds and Peter Milner at McGill University, in Montreal, way back in the early 1950s. They had heard in a lecture that a brain network then known as the reticular activating system (RAS) would motivate rats to learn mazes better if it was stimulated electrically. Increasing the activity of the cells in this network appeared to make rats more alert and more successful at remembering the maze. Eager to study this for themselves, Olds and Milner placed electrodes into rat brains (similarly to the way I would later do, though I was measuring activity rather than adding electricity to stimulate the brains of my rats). They tried to place the electrodes so they could stimulate the RAS.
    Once these electrodes were implanted and the rats had recovered from the surgery, the researchers placed the animals, one at a time, in a box. Each corner was labeled: A, B, C, D. Whenever the rat wandered over to corner A, the scientists hit a button to electrically stimulate its brain. Most of the rats just wandered aimlessly. But one particular rat would repeatedly return to corner A, especially during the stimulation, as though the stimulation had made this corner very attractive.
    Olds and Milner began to wonder if they’d misplaced the electrode in this rat. They decided to examine its brain closely to see where the probe had landed. When the researchers dissected its brain, they found that they had indeed put the electrode in the wrong spot, accidentally landing in a region known as the medial forebrain bundle (MFB).
    Initially, the researchers thought they’d discovered that the MFB made rats curious or interested. And that was probably part of what was going on. But in order to try to figure out exactly what was happening, they next deliberately implanted electrodes in this region in other rats. Instead of stimulating their brains manually, however, Olds and Milner put levers in the rats’ cages to allow them to stimulate themselves. And, once the scientists let the rodents start pressing the lever, some began hitting it up to seven hundred times an hour. 2
    Though these findings have been exaggerated—in both the scientific literature and popular press—to make it look like no rat could ever “just say no” to this type of self-stimulation, many rats actually didn’t learn to self-stimulate and couldn’t be trained to do it. As with drug addiction, this is not a phenomenon that can be understood in isolation from the rest of the environment, even in rats. And as with drug addiction, the truly compulsive behavior was seen only under specific conditions.
    Nonetheless, Olds and Milner soon realized that they might be on to something much bigger than a way to enhance learning. They’d discovered some kind of joy spot—in fact, the area soon became known as the brain’s “reward” or “pleasure” center. Later, in the 1960s, other researchers would discover that the most abundant neurotransmitter in this region was dopamine and that the MFB carried signals between regions we now think are involved in pleasure and desire, such as the nucleus accumbens.
    The rats’ behavior with the lever appeared to be a model for reward that could be used to study addiction. Now all that was left to do, it seemed, was to figure out how different drugs interact with dopamine and then discover ways to block this. Addiction might be cured, once and for all.
    Over time, however, as you’ve probably guessed by now, it’s a lot more complicated than we initially thought. When dopamine’s prominent role in reward was proposed, there were only about six known neurotransmitters: dopamine, norepinephrine, serotonin, acetylcholine, glutamate, and GABA. Now there are more than a