Summary: Cocaine is a potent stimulant and a substance of abuse. However, contrary to common belief, it causes severe addiction only in 20% of the users. Thus, researchers knew that the brain of 20% of individuals must be lacking some counteracting mechanism. Early studies on addiction have confirmed that the dopamine reward pathway plays a vital role in addiction. Accumulation of dopamine in specific parts of the brain causes the high and plays a role in the consolidation of memory of these experiences. In the new study, researchers found that serotonin helps counter addiction caused by dopamine accumulation. Furthermore, they found that dysregulation of serotonin in some individuals makes them prone to addiction. It means that correcting this serotonin dysregulation may help overcome addiction.
Contrary to common belief, studies show that just 20% of regular cocaine users get addicted. Of course, most have psychological dependence, but very few of them have so-called physiological dependence1.
Psychological dependence is when a person frequently abuses a particular substance as it brings pleasure. However, a person can give up that substance without many health issues. On the other hand, in physiological dependence, one may have severe withdrawal syndrome, sometimes making it almost impossible to give up the substance of abuse.
The central role of dopamine and dopaminergic pathways in addiction is well known. Dopamine is a hormone responsible for controlling the activity of brain neurons. Thus, if a person is in a low mood, the mild dopamine release helps stimulate the brain and uplift the mood. Cocaine causes euphoria or high by promoting the buildup of dopamine in certain parts of the brain2.
Among various brain centers, the limbic system plays a particularly important role in the development of addiction. This is because the limbic system contains vital memory centers like the hippocampus and amygdala that help people remember what brings pleasure. Moreover, the limbic system is rich in dopamine-producing cells2.
Figure 1 Cocaine addiction, the role of dopamine and various brain centers2
In all human body systems, the balance is maintained with the help of two opposing systems. Thus, in the autonomic system, sympathetic nerves may stimulate the heart, and parasympathetic may calm down the heart. Similarly, there are stimulatory and inhibitory neurons. Thus, researchers knew that the brain must have some opposing mechanism to counter the excitatory effect of dopamine on various brain centers.
In some early experimental studies, they found that serotonin helps minimize various dopamine effects. Dopamine drugs are already being used to help people with a withdrawal syndrome. Now researchers think that adding serotonin-increasing medications to treatment may also help counter the urge to use substances and overcome addiction3.
Researchers experimented on mice to understand how serotonin may help counter the addictive actions of cocaine and neutralize specific ill effects of high dopamine. First, they taught mice to start consuming cocaine, but after taking cocaine, they were punished by giving an unpleasant electric current. At the end of the study, researchers found that 80% of mice stopped taking cocaine, and quite like humans, 20% continued despite the unpleasant effects of electric current.
Further, they repeated the experiment in mice that had issues with the serotonin transporter, and they found that far more mice in that particular group, 60%, got addicted. However, they also saw that if they administered serotonin to these mice, the addiction rate again fell to 20%. Thus, the experiment proved that serotonin is one of the major neurotransmitters that help prevent addiction1.
When a person consumes cocaine, there is an increase in dopamine in certain brain parts, causing a high and feeling of pleasure. Unfortunately, this experience is remembered by the limbic system, resulting in repeated cocaine abuse. However, serotonin acts as a natural balancer. It helps prevent the consolidation of these experiences in the brain. It means that therapies targeting serotonin may help prevent or overcome addiction in a large number of cases.
Frequently asked questions
Why is cocaine so addictive?
Cocaine causes a buildup of dopamine in certain parts of the brain, which produces the high. The limbic system, which holds memory centers such as the hippocampus and amygdala and is rich in dopamine-producing cells, remembers what brought that pleasure. That stored memory of the experience is what pulls a person back to use cocaine again and again.
Does everyone who uses cocaine get addicted?
No. Studies show that only about 20% of regular cocaine users develop a severe addiction. Most users have a psychological dependence: they use it because it brings pleasure but can give it up without many health problems. Few develop physiological dependence, where withdrawal becomes severe enough that quitting can seem almost impossible.
How does serotonin affect cocaine addiction?
Serotonin acts as a natural balancer against dopamine. It helps keep the brain from locking in the memory of the cocaine high. In mouse experiments, 20% kept taking cocaine despite a punishment. In mice with serotonin transporter problems, 60% became addicted, and giving these mice serotonin brought the rate back down to 20%.
What neurotransmitter is most linked to addiction?
Dopamine sits at the center of addiction. The dopamine reward pathway drives the high and helps the brain store the memory of the experience. Serotonin is its counterweight: it limits several of dopamine’s effects, and when serotonin is dysregulated, a person becomes more prone to addiction. Researchers think serotonin-increasing medications may help counter the urge to use.
References
1. Li Y, Simmler LD, Van Zessen R, et al. Synaptic mechanism underlying serotonin modulation of transition to cocaine addiction. Science. 2021;373(6560):1252-1256. doi:10.1126/science.abi9086
2. Nestler EJ. The Neurobiology of Cocaine Addiction. Sci Pract Perspect. 2005;3(1):4-10.
3. R.B. R, B.E. B, M.H. B. Dual dopamine/serotonin releasers: Potential treatment agents for stimulant addiction. – PsycNET. Experimental and clinical psychopharmacology. Published online 2008. Accessed October 16, 2021. https://psycnet.apa.org/doiLanding?doi=10.1037%2Fa0014103