How The Brain Protects Itself Against Cocaine


Ben Taub


Ben Taub

Freelance Writer

Benjamin holds a Master's degree in anthropology from University College London and has worked in the fields of neuroscience research and mental health treatment.

Freelance Writer

519 How The Brain Protects Itself Against Cocaine
Cocaine can be highly addictive – but not as addictive as it would be if we didn't have microglia. Mukhina Viktoriia/Shutterstock

The things we put into our bodies for fun can have some pretty nasty side-effects – not least of all those that come in a white powder and go up your nose. Fortunately, our brains have a contingency plan that kicks into action whenever our irresponsible tendencies get the better of us and we decide to use drugs. In a new study published in the journal Neuron, a team of researchers has identified the mechanism by which the brain protects itself against the effects of cocaine, potentially opening the door to new treatments for substance abuse disorders.

According to the study authors, this inbuilt defense is controlled by microglia, a type of immune cell found in the brain and central nervous system. “Cocaine activates these microglia, which causes the release of an inflammatory signal which then tries to reverse the changes that cocaine is inducing in the neurons,” said lead researcher David Stellwagen, from the Research Institute of the McGill University Health Centre (RI-MUHC) in Montreal, in a statement.


Drugs such as cocaine stimulate a massive release of neurotransmitters such as dopamine, which affects the brain’s so-called reward circuit, leading to pleasurable sensations. Persistent use of cocaine can then cause changes to occur in a brain region called the nucleus accumbens (NAc), which is a vital component of this reward circuit.

More specifically, cocaine abuse strengthens the connections – or synapses – between neurons in the NAc, resulting in decreased sensitivity to the drug as well as the development of highly ingrained behaviors, usually involving a desire to continually seek out the substance.

However, microglia release an inflammatory signal called tumor necrosis factor alpha (TNF-a), which serves to decrease synaptic strength in the NAc, thereby leading the study authors to hypothesize that these cells may play a role in staving off the effects of cocaine.

Cocaine affects synaptic strength in a brain region called the nucleus accumbens. adike/Shutterstock


To test this, they monitored the activity in the NAc of mice when given cocaine, and found that, shortly after receiving the drug, levels of TNF-a in this part of the brain skyrocketed, resulting in a reduction in synaptic strength.

They then repeated the experiment using mice that had been genetically engineered to lack TNF-a, finding that, immediately after receiving cocaine, synaptic strength in the NAc increased. As a consequence, these mice displayed a much greater tendency to become addicted to the drug than regular mice.

The researchers therefore conclude that microglia, via the release of TNF-a, are activated by cocaine in order to block its damaging effects – something which Stellwagen says could be the main factor preventing “casual use [turning] into chronic dependence.” However, the team also found that “the microglia response fades over time,” meaning that this ability to stave off addiction is reduced if a person continually uses cocaine over long periods.

Amazingly, though, the researchers found that they were able to reactivate the microglia in cocaine-dependent mice using a compound called monophosphoryl lipid A (MPLA), resulting in a reduction of their drug-seeking behaviors.


Though these results would need to be replicated in humans before we get too excited, the study authors claim that their data “suggest that MPLA could reduce the motivation to acquire drugs and be used to prevent relapse, a significant problem in the treatment of addiction.”


  • tag
  • cocaine,

  • addiction,

  • dopamine,

  • synapse,

  • drugs,

  • microglia,

  • nucleus accumbens,

  • reward circuit