Pier Vincenzo Piazza and Olivier Manzoni, of the Neurocentre Magendie in Bordeaux, and their team of researchers are the first to discover an existing correlation between consistent impairment of synaptic plasticity in the brain and the transition to addiction.

“The results from the teams at Neurocentre Magendie call into question the hitherto held idea that addiction results from pathological cerebral modifications which develop gradually with drug usage. Their results show that addiction may, instead, come from a form of anaplasticity, i.e. from incapacity of addicted individuals to counteract the pathological modifications caused by the drug to all users.”

In 2004, this research team discovered that addictive behaviors are not restricted to the human species, but similar behaviors can be found in rats that self-administer cocaine.

From this breakthrough, Piazza and Manzoni have now discovered the first known biological mechanisms for addiction, where the transition from regular and controlled drug use can transform into a loss of control over cocaine consumption.

Researchers compared addicted and non-addicted rats and found that the brains of rats with an addiction to cocaine are permanently unable to produce a form of plasticity called long term depression (LTD).

LTD is a neurophysiologic activity-dependent reduction in the efficacy of neuronal synapses that lasts hours or more. It may occur as a result of strong synaptic stimulation or from persistent weak synaptic stimulation. It is required for learning to occur by developing engrams, which are a hypothetical means by which memory traces are stored as biochemical changes in the brain in response to external stimuli. Basically, LTD can no longer be achieved with persistent drug use.

Nevertheless, LTD is not altered after only a short period of cocaine use, but a significant deficit can be found in all users with prolonged use. A lack of LTD allows behavior to become less flexible which can easily lead to addiction.

“The brain of the majority of users is able to produce the biological adaptations which allow to counteract the effects of the drug and to recover a normal LTD. By contrast, the anaplasticity (or lack of plasticity) exhibited by the addicts leaves them without defences and hence the LTD deficit provoked by the drug becomes chronic. This permanent absence of synaptic plasticity would explain why drug seeking behaviour becomes resistant to environmental constraints (difficulty in procuring the substance, adverse consequences of taking the drug on health, social life, etc.) and consequently more and more compulsive. Gradually, control of the taking of the drug is lost and addiction appears.”

Consequently, the team is confident that new treatments for addiction can be developed by studying the brains of non-addicts, while a good understanding of the biological mechanisms that enable addiction can lead to ways counteract the anaplastic state that leads to addiction.

Addiction: A Loss of Plasticity of the Brain?
Long-term depression

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