How serotonin curbs cocaine addiction

Date:
September 9, 2021
Source:
Universite' de Gene`ve
Summary:
Contrary to common thinking, cocaine triggers an addiction only in
20% of the consumers. But what happens in their brains when they
lose control of their consumption? Thanks to a recent experimental
method, neuroscientists have revealed a brain mechanism specific
to cocaine, which has the particularity of triggering a massive
increase in serotonin in addition to the increase in dopamine
common to all drugs. Indeed, serotonin acts as an intrinsic brake
on the overexcitement of the reward system elicited by dopamine,
the neurotransmitter that causes addiction.



FULL STORY ========================================================================== Contrary to common thinking, cocaine triggers an addiction only in
20% of the consumers. But what happens in their brains when they lose
control of their consumption? Thanks to a recent experimental method, neuroscientists at the University of Geneva (UNIGE), Switzerland,
have revealed a brain mechanism specific to cocaine, which has the particularity of triggering a massive increase in serotonin in addition
to the increase in dopamine common to all drugs. Indeed, serotonin acts
as an intrinsic brake on the overexcitement of the reward system elicited
by dopamine, the neurotransmitter that causes addiction. These results
are published in the journal Science.


========================================================================== Addiction is defined as the compulsive search for a substance despite
the negative consequences, whereas dependence is characterised as the occurrence of a withdrawal symptom -- the physical effects of which
vary greatly from one substance to another -- when consumption is
stopped abruptly. It thus affects everyone, whereas addiction affects
only a minority of users, even after prolonged exposure. For example,
it is estimated that 20% of cocaine users and 30% of opiate users are
addicted. "The same principle applies to all potentially addictive
products," says Christian Lu"scher, a professor in the Department
of Basic Neurosciences at the UNIGE Faculty of Medicine, who led the
research. "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." Addiction triples without serotonin To assess how cocaine addiction arises
in the brain, the research team developed a series of experiments. "Most
of the time, scientific experiments aim to reproduce a systematic
mechanism. Here, the difficulty lies in observing a random phenomenon,
which is triggered only once in five times," explains Yue Li, a researcher
in Christian Lu"scher's laboratory and first author of the study.

The scientists first taught a large group of mice to self-administer
cocaine voluntarily, and then added a constraint: each time they self-administered cocaine, the mice received a slightly unpleasant
stimulus (electric shock or air jet). Two groups then emerged: 80% of
the mice stopped their consumption, while 20% continued, despite the unpleasantness. "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.

The experiment was repeated with mice in which cocaine was no longer
linked to the serotonin transporter, so that only dopamine increased
when the substance was taken. 60% of the animals then developed an
addiction. The same was found in other animals with a reward system
stimulation protocol that did not affect serotonin. "If serotonin is administered to the latter group, the rate of addiction falls to 20%,"
says Christian Lu"scher. "Cocaine therefore has a kind of natural brake
that is effective four times out of five." A delicate synaptic balance
When cocaine is consumed, two forces are at work in the brain: dopamine
on the one hand, whose sudden increase leads to compulsion, and serotonin
on the other, which acts as a brake on compulsion. Addiction therefore
occurs when an imbalance is created between these two neuroregulators
and dopamine overtakes serotonin.

"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 Christian Lu"scher.

What about other drugs? Apart from the increase in dopamine, each
substance has its own specificity and effect on the brain. If the
addictive effect of cocaine is naturally reduced by serotonin, what
about other drugs? The Geneva neuroscientists will now look at opiates --
which are more addictive than cocaine -- and ketamine, which is much less
so. The aim is to understand in detail how the brain reacts to these
drugs and why some people are much more vulnerable to their harmful
effects than others.

========================================================================== Story Source: Materials provided by Universite'_de_Gene`ve. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Yue Li, Linda D. Simmler, Ruud Van Zessen, Je'ro^me Flakowski,
Jin-Xia
Wan, Fei Deng, Yu-Long Li, Katherine M. Nautiyal, Vincent Pascoli,
Christian Lu"scher. Synaptic mechanism underlying serotonin
modulation of transition to cocaine addiction. Science, 2021; 373
(6560): 1252 DOI: 10.1126/science.abi9086 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210909141233.htm

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