The research — out of University of British Columbia (UBC) and the University of Calgary — was recently published in Nature Neuroscience. UBC PhD candidate Andrea Globa said they wanted to test what type of learning happened in the reward circuitry of the brain involved with addiction.
“Researchers are pretty confident now that addiction is a form of learning where the same mechanisms involved in regular learning kind of go haywire and are used in a pathological way in a circuit of the brain,” said Globa. “We wanted to figure out what was happening in the cellular and molecular level.”
They zeroed in on a specific protein called cadherin, which Globa described as a sort of glue that can connect cells at the points at which they communicate, otherwise known as synapses.
“To put it simply, in order to learn something you have to make these synaptic connections stronger and this can involve adding more of this protein – cadherin – to the synapses,” she said.
Previous studies have shown that people with substance abuse problems tend to have more genetic mutations associated with cadherin.
The researchers set up three small chambers. Then they gave mice with extra cadherin in their brains a dose of cocaine inside only one of the rooms. Over time, they expected that the mice with more of that “glue” would create a strong connection between that specific chamber and the high they got from the drugs.
Instead, they found that the mice wandered between all three rooms equally as if they weren’t seeking out the drug.
“Normal mice (without the added cadherin) would always move towards the chamber where they received the cocaine, which would indicate that they were looking for that high,” said Globa. “But our mice that had too much of the cadherin protein didn’t behave in this way. They explored all the rooms evenly.”
Upon further research, they concluded that the extra cadherin was muddling up the mice brains and taking up too much room, preventing them from making strong connections.
“We know that there’s a certain amount of real estate at these synapses where if you don’t remove the weaker receptor, there’s no room for the more sensitive receptor to get inserted,” she said.
“The long and short of it is that if you have too much cadherin, it holds onto this old type of receptor and prevents the more sensitive receptor from getting to the right spot. And as a result there’s no strengthening of these synapses, and there’s no learning and there’s no addiction.”
Dr. Shernaz Bamji, who supervised the UBC portion of the study, said the findings help shed light on the biochemical reasons behind addiction.
“If two people take the same drug, one might have a predisposition to addiction and the other person might not have that predisposition towards addiction. And that has more to do with biology and biochemistry than just being ‘weak-willed,’” she said.
But Globa warns that this doesn’t mean that they can now develop a miracle drug that’ll increase cadherin in human brains to make people less susceptible to addiction, because our brains still need the ability to learn. She said more research needs to be done to discover whether there are other proteins that only affect certain cells or circuits in brains, so that the rest of our brains remain unaffected.
Next, the team hopes to research how to reduce a mouse’s propensity for cocaine once it is already addicted to the drug.