Researchers have created mice that appear impervious to the lure of cocaine.
Even after the genetically engineered animals were given the drug repeatedly, they did not appear to crave it the way typical mice do, a team reports in Nature Neuroscience.
"They didn't keep going into the room where they received the cocaine and they seemed to be just as happy exploring all around the cage," says Shernaz Bamji, a professor in the Department of Cellular and Physiological Sciences at the University of British Columbia in Vancouver.
"Addiction is a form of learning," Bamji says. And somehow, these mice never learned to associate the pleasurable feelings produced by cocaine with the place where they received the drug.
The result was startling because the scientists thought these mice would be especially susceptible to addiction. "We repeated the experiment several times to see if we had made a mistake," Bamji says.
The reason for the team's surprise had to do with proteins that affect learning.
The animals had been genetically engineered to produce high levels of proteins called cadherins in the brain's "reward circuit," which plays an important role in addiction. And genetic studies have suggested that people with high levels of cadherins are more susceptible to drug addiction.
Cadherins act a bit like glue, binding cells together. Usually this glue enhances learning by strengthening the connections, or synapses, between brain cells.
The reward circuit is involved in both the sensation of pleasure triggered by addictive drugs, and the craving that propels addicts to seek out these drugs.
So the researchers expected the mice with extra cadherins in the reward circuit to become instant addicts. "We thought, hey, more glue, stronger synapses, more learning, more addiction," Bamji says. "But what we actually saw was the opposite."
A close look at the brains of the mice showed why. It turned out that too much glue was actually gumming up the synapses in the reward circuit so they couldn't get stronger. As a result, the mice never learned to crave cocaine, even though it made them feel good.
The finding may help explain why certain people are susceptible to addiction, says Bamji. "Addiction is not just bad judgment, but really is more to do with our biology and our biochemistry," she says.
And the results also suggest that it may be possible someday to treat addiction by changing the way learning occurs in certain areas of the brain.
ROBERT SIEGEL, HOST:
Scientists have genetically engineered mice that do not get addicted to drugs. Even when these animals are given cocaine, they don't learn to crave it the way other mice do. NPR's Jon Hamilton reports.
JON HAMILTON, BYLINE: Brain scientists sometimes describe addiction as a learning disorder.
SHERNAZ BAMJI: Addiction is a form of learning that goes a bit haywire in a particular circuit of the brain.
HAMILTON: Shernaz Bamji is a researcher at the University of British Columbia. She says when people or animals take a drug like cocaine, they quickly learn that it produces a pleasurable sensation. But in addicts, something called the reward circuit in the brain learns the lesson too well, so an addict will seek the drug over any other reward. Bamji says that's usually what happens when mice learn to associate a special chamber in their cage with cocaine.
BAMJI: Normal mice always gravitate towards that chamber where they receive the drug.
HAMILTON: So Bamji and her team were surprised when they realized that some genetically-altered mice seemed impervious to the lure of cocaine.
BAMJI: They didn't keep going into the room where they received the cocaine, and they just seemed to be just as happy exploring all around the cage.
HAMILTON: The result was startling because the scientists had expected these mice to be especially susceptible to addiction. The reason - these animals had been programmed to produce high levels of a protein called cadherin in their brains. Cadherin acts a bit like glue. And Bamji says this glue usually strengthens the connections between brain cells, which are called synapses.
BAMJI: When you're learning something, you have to make your synapses stronger, and this involves adding more glue to the synapse.
HAMILTON: So Bamji's team figured the mice with extra glue would be instant addicts.
BAMJI: What we thought was that, hey, more glue, stronger synapses, more learning, more addiction. But what we actually saw was the opposite.
HAMILTON: Bamji says a close look at the brains of these mice showed why. Too much glue actually gooped up the synapses in the reward circuit so they couldn't get stronger. As a result, the mice never learned to crave cocaine even though it made them feel good. Bamji says the finding, which appears in the Journal Nature Neuroscience, may help explain why certain people are susceptible to addiction.
BAMJI: Addiction is not just bad judgment but, really, is more to do with our biology and our biochemistry.
HAMILTON: Bamji says the study also suggests it may be possible someday to treat addiction by changing the way our brains learn. Jon Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.