Only one in five people get addicted to cocaine thanks to the protective effects of serotonin on the brain, according to a team of researchers from the University of Geneva, Switzerland. These results are published in the journal Science (1).
Contrary to popular belief, not everyone that tries cocaine gets addicted. In fact, only about 20% of cocaine users ever become addicted. The same is true for other drugs, like opioids and even alcohol. “Here in Switzerland, for instance, almost all adults consume alcohol from time to time, which is a strong stimulator of the reward system. However, only a small proportion of us will become alcoholics”, said Christian Lüscher, lead author from the Department of Basic Neurosciences at the University of Geneva, Switzerland.
Why? What happens in the brain that protects some people against addiction but not others? So far, researchers haven’t been able to explain the mechanism behind it, but now Lüscher’s team have uncovered a mechanism specific to cocaine that triggers a massive release of serotonin (in addition to the release of dopamine common to all drugs). The researchers believe serotonin works to stop the reward system from getting overexcited due to the presence of dopamine. In other words, serotonin dampens the addictive effect of dopamine.
To assess how cocaine addiction influences the brain, the researchers taught a group of mice to self-administer cocaine. Once the mice learnt this trick, they added a constraint: each time mice tried to get cocaine, they would receive an unpleasant electric shock. Soon, two groups were obvious: 80% of the mice stopped completely, while the remaining 20% continued despite the painful experience. “This compulsive behaviour is precisely what defines addiction, which affects 20% of individuals, in mice as well as in humans”, emphasises Vincent Pascoli, a scientific collaborator in the Geneva group and co-author of this study.
Repeating the experiment with mice where the serotonin effect was blocked yielded very different results. In this case, 60% of animals continued looking for cocaine and developed an addiction. However, when serotonin was given to the mice, the rate of addiction returned to 20%. “Cocaine has a kind of natural brake that is effective four times out of five”, said Lüscher.
This means cocaine addiction is the result of a fight between two sides. On the one hand, dopamine, which leads to compulsion, and on the other, serotonin, which acts as a break. In simple terms, addiction happens when dopamine wins. “Actually, dopamine triggers a phenomenon of synaptic plasticity through the strengthening of connections between synapses in the cortex and those in the dorsal striatum. This intense stimulation of the reward system then triggers compulsion. Serotonin has the opposite effect by inhibiting the reinforcement induced by dopamine to keep the reward system under control”, explains Lüscher.
This mechanism works with cocaine, but not necessarily with other drugs. Each substance has its own effect on the brain. The team is keen to continue their work, looking into opioids (much more addictive) and ketamine (less addictive than cocaine). The aim is to figure out how the brain reacts to these drugs, why some people are more susceptible to their effects than others and how this knowledge could potentially be used to treat drug users.
(1) Li Y, Simmler L, van Zezzen R, Flakowski J, Wan J, Deng F, Li Y, Nautiyal K, Pascoli V, Luscher C (2021) Synaptic mechanism underlying serotonin modulation of transition to cocaine addiction. Science, 373, 1252-1256