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Sticky molecules and the 'cocaine proof' mouse

Researchers in Germany dubbed a certain variant of the CAMK4 gene the ‘cocaine gene' after discovering that cocaine addicts were 25% more likely to carry this variant than non-users.

A biological basis for cocaine addiction.

Addiction is a complex disease and genetics almost certainly play a role, not only in its severity, but in its likelihood of an individual becoming addicted in the first place. Cocaine is rated as the second most addictive narcotic behind heroin. So does cocaine addiction run in the blood? Or, more specifically, the genes?

Back in 2008, researchers at the Central Institute of Mental Health in Mannheim, Germany dubbed a certain variant of the CAMK4 gene the ‘cocaine gene’ after discovering that cocaine addicts were 25% more likely to carry this variant than non-users. Rainer Spanagel, professor of psychopharmacology at the institute and leader of the study, concluded that carriers of this gene variant had a “significantly increased likelihood of becoming addicted.”

The ‘cocaine-proof’ mouse

This ignited a flurry of research into the biological basis of cocaine abuse. Most recently, the focus has been on the role of cadherins – a certain type of protein in the brain – after Canadian scientists accidentally created a ‘cocaine-proof’ mouse.

Cadherins play an important role in a process called ‘cell adhesion’. Their role is to form junctions that bind cells within tissues together. In layman’s terms, cadherins act a bit like glue, and this glue is very important in the brain’s learning process. Through a process of ‘positive reinforcement’ our brains are conditioned to repeat positive experiences which yield pleasurable results. Cadherins mediate this learning by strengthening the synapses between brain cells, making their connections more concrete.

Dr Shernaz Bamji and her collaborators at the University of British Columbia engineered the brains of mice in the lab so that they would have more cadherins, and confidently predicted that they would be more susceptible to cocaine addiction, as their pleasure response learning would be greater.

Bamji was flummoxed, however, when her mice actually displayed fewer addictive behaviours. When given the choice between a room they had learned to associate with receiving cocaine and other rooms in a maze, they were indifferent to the cocaine associated room, compared with their average levelled cadherin counterparts, who repeatedly returned for more cocaine. It was the non-altered mice that became addicted, and not their genetically modified cohorts.

These mice never learned to crave cocaine, even though they still experienced the high

Taking a closer look at the brains of the engineered mice it turned out that the overload of glue had actually ‘jammed up’ the neural pathways, thus inhibiting the cell adhesion process, thus preventing the connections from being formed. As a result, these mice never learned to crave cocaine, even though they still experienced the high.

So what does this mean for humans? Is there any way these results can be applied? Well the intricacies of that translation still need some working out. The increase of cadherins may have the potential to inhibit addiction, but by the same token the potential to damage other learning behaviours. And genetically modifying human brains is clearly out of the question.

This said, the implications of the research are still exciting. They open up a target for further research and the possibility for future treatments, and possibly even preventative vaccines. Research continues.

City Addictions, April 14, 2017

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