Abusing drugs like cocaine can cause a harmful restructuring of the brain as new connections form that reinforce the desire to repeatedly use the drug, resulting in cravings and contributing to addiction. And while the continual reshaping of neural pathways is something that goes on inside all of our brains, new research suggests that the connections that form in response to cocaine use are driven by a unique and unexpected mechanism.
According to a new study in the journal Biological Psychiatry, drug-related memories are encoded into the brain thanks to the activity of astrocytes. Named for their star-like shape, astrocytes are generally thought of as support cells that help neurons to function, yet the discovery of their role in creating new brain connections – or synapses – opens all sorts of new possibilities for the treatment of drug addiction.
In truth, astrocytes are much more than just the brain’s janitors. During the early stages of the brain’s development, these cells release signaling proteins called thrombospondins (TSPs) that facilitate the formation of synapses. Yet TSP levels decline greatly once the brain is fully developed as astrocytes take a back-seat in the synapse formation process.
Intriguingly, though, a 2014 study found that astrocyte-released TSP increases greatly in the brains of rats immediately after they are given cocaine. This finding gave rise to the so-called “neural rejuvenation hypothesis,” which proposes that certain drugs trigger early developmental mechanisms in order to restructure the adult brain circuits involved in addiction.
To investigate, the authors of the latest study observed the activity of astrocytes in the brains of rats as they self-administered cocaine, while also monitoring the animals’ addictive behaviors. Unsurprisingly, the rodents quickly developed a craving for the drug and repeatedly searched for it after it was taken away.
This new behavior coincided with synaptic remodeling in an area of the brain called the nucleus accumbens, which is part of the reward circuit and plays a role in both learning and addiction. In other words, cocaine-related memories had become encoded into the rats’ brains, causing them to become hooked on the drug.
However, by blocking the release of TSP in the nucleus accumbens, the researchers were able to prevent the formation of new synapses in response to cocaine. As a consequence, the rats did not develop any addictive behaviors and did not continue to search for the drug after it had been removed.
Summing up the importance of interrupting this process, study author Yan Dong explained in a statement that “memories associated with drugs of abuse can be extremely durable and often trigger drug relapse even after long abstinence.” Having revealed the role of astrocytes in creating these memories, the researchers believe it may now be possible to target this pathway in order to prevent relapse in those recovering from addiction.
