The Complexity of Nature's Human Neuro-wiring

"Addiction is a form of learning in the reward circuits of the brain. Where you don't get synapse strengthening, you aren't getting learning and you aren't getting addiction."
"Simply increasing cadherin would likely prevent [addicts] from learning anything new. That's not a very good trade-off."
Dr. Shernaz Bamji, neuroscientist, professor, University of British Columbia, Vancouver, B.C.

Vice.com

"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."
"We wanted to figure out what was happening in the cellular and molecular level."
UBC PhD candidate Andrea Globa  

Professor Bamji and her team of collaborators have been working with genetically engineered mice in an effort to understand what motivates human beings to become addicted to habitual drug use. Their latest study was published recently by the journal Nature Neuroscience. Building on previous work done at Johns Hopkins University in Baltimore, Maryland, the UBC team discovered that people with certain genetic mutations associated with a protein class called cadherins in their brains are more susceptible to substance abuse.

The mice they used in their study are unlike normal mice in that even after repeated injections of cocaine over a period of time, their behaviour showed no symptoms of addiction. This led the researchers to the assumption that genetics may be at play in the onset of addictive behaviour. Normal as well as the genetically engineered mice were injected with cocaine while in one area of a multi-sectioned cage. Mice were placed in the other section on alternating days to be injected with saline. Six days of alternating treatment passed and the mice were permitted to move freely to any of the cage's sections.

The cocaine-associated section was chosen preferentially by the normal mice while the high-cadherin mice bypassed that chamber, leading to the theory that the presence of additional cadherin interferes with the learned response to cocaine. "Normal mice always gravitate to the chamber where they received the drug, looking for that high, but the mutant mice didn't", explained Dr. Bamji. Cadherin interfered with the capacity of a specialized protein receptor to function at the point where neurons communicate chemically to form memories.

The brain's learning circuitry was unable to retain the pleasurable memory of cocaine when the connection between synapses failed to connect. The research team's conclusion has the potential to lead to a test identifying which individuals may be at greatest risk of addiction. With that knowledge people could be empowered to act on that personalized information. That a biochemical model for addiction exists and those people should proceed with the caution their genetic risk deserves.

Cadherin aids in the binding of cells and thus plays a vital role where brain circuits are strengthened during learning -- including learning that specific drugs deliver pleasure. Dr. Bamji had proceeded with the study on the theory that higher levels of cadherin present in the engineered mice might lead the way to increased addictive behaviour. The study results, however, indicated the reverse to be true. The researchers had engineered mice capable of producing excessive cadherin proteins in their brains.

Despite which, the engineered mice with increased cadherin did not respond to the tests by gravitating to the cage's chamber where they were introduced to cocaine, unlike the behaviour of the normal mice with less cadherin, but with the genetic marker leading to increased addiction. Still, a problem arose because of the fact that many synapses in the brain use the same learning strategy. If ongoing research reveals a protein or enzyme in the brain acutely specific to addiction functioning solely in the brain's reward circuitry, that protein or enzyme could present as a medication target.

Until then, it is highly unlikely that a strategic use of some chemical in pill form to medicate people with a genetic propensity to addiction could be formulated to offer protection against a very real harm mechanism  recognized as addiction.

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