Addiction, whether to drugs or alcohol, has its roots in the brain. Brain chemistry and activity is significantly altered by the use of drugs or alcohol and researchers looking for the causes of addiction have studied changes in the brain extensively in the search to understand it and develop treatments. In new research from scientists at the University of British Columbia, a genetically engineered mouse has been created that seems to be addiction proof. The team set out to look at synapses in the brain’s reward circuit. The goal was to prove their hypothesis that a protein called cadherin would strengthen certain synaptic connections and thus make mice more likely to become addicted to cocaine, but their results were much different than expected.
The reward circuit in the brain is huge part of addiction. If there wasn’t some kind of reward, such as a high or other euphoria involved with drugs, people wouldn’t learn to continue seeking that feeling and subsequently become addicted. While there is a stigma that addiction is a character flaw or an unwillingness on the part of an addict to make better choices, it’s actually all about how the brain processes the substance. Shernaz Bamji, a Professor in the Department of Cellular and Physiological Sciences Learning at the University of British Columbia, ran a study where normal mice were injected with cocaine on a daily basis. Another group of mice were altered to have higher levels of cadherin.
Immediately after being injected with cocaine, the mice were placed in a cage that had three separate areas, but they were always placed in a specifically decorated section. In this way they came to associate the drug and this one room. Even though they were placed in this specific room while still under the influence of the coke, they were allowed to roam around the cage. The normal mice gravitated more to the decorated room, since they had formed the association between the drug and that specific room. The mice with higher cadherin levels did not. They seemed to have no connection to the room and no strong memories of the effect of cocaine on their brain. It was essentially the exact opposite of what the researchers had expected.
Through analysis of brain tissue in the altered mice they found that the extra cadherin, rather than shoring up the synapses in the reward circuit, actually kept a specific neurochemical receptor from breaking through the cell membrane. Without this receptor being able to penetrate to the interior of the cells, the cells did not bind together as expected, the synapse did not grow stronger and the happy memory the cocaine just didn’t “stick.”
Graduate student Andrea Globa, a co-lead author of the study, explained, “Through genetic engineering, we hard-wired in place the synapses in the reward circuits of these mice. By preventing the synapses from strengthening, we prevented the mutant mice from ‘learning’ the memory of cocaine, and thus prevented them from becoming addicted.”
Previous research has shown that addicts have more genetic mutations that affect cadherin levels and cell adhesion, so the result at UBC is yet another study that sheds light on the roots of addiction and how some people are just more likely to get addicted. It’s also another piece of evidence to show that addiction is not a matter of a person not trying hard enough or not caring about the impact of their addiction on family and friends. In this study, cadherin kept mice from becoming addicted however, that doesn’t mean human levels of cadherin can be increased and the problem of addiction will be solved. Dr. Bamji stated, “For normal learning, we need to be able to both weaken and strengthen synapses. That plasticity allows for the pruning of some neural pathways and the formation of others, enabling the brain to adapt and to learn. Ideally, we would need to find a molecule that blocks formation of a memory of a drug-induced high, while not interfering with the ability to remember important things.” The video below has more information, check it out.
Sources: University of British Columbia, Huffington Post, Nature Neuroscience