A team of researchers at UCSF studying the effects of cocaine on mice have found that after mice are given just one dose of the drug, their brains commence a rapid rewiring of brain circuits and spinal formation.
The researchers found that cocaine physically altered the composition of the prefrontal cortex, an area associated with decision-making and memory. These findings were supported by a series of experiments in which the mice showed significant behavioral changes as well. The results could shed light on the biological effects of initial cocaine exposure in humans.
In the experiment, mice were directed to a “conditioning box” composed of two adjacent chambers that differed in smell and design. After observing which compartment the mice favored, the researchers administered the mice one dose of cocaine in the other room. The mice then favored the new room, presumably seeking out more of the drug.
According to Linda Wilbrecht, an assistant professor of psychology and neuroscience at UC Berkeley and the lead author of the study, the animals that showed the most obvious preference for the room in which the drug was administered also displayed the most significant growth of dendritic spines, or tiny, twiglike structures that connect neurons and promote intercellular communication.
“This is certainly the best demonstration of how drugs of abuse alters the brain not just functionally but structurally,” said Hans Crombag, a neuroscientist at the University of Sussex, who was not involved in the study.
Though scientists have long known that cocaine has physical effects on the brain’s wiring, the researchers were shocked at how quickly the effects took hold. They were especially interested in modifications to the rodents’ prefrontal cortices. Specifically, they suggest that cocaine increases activity in an area of the brain responsible for developing what the study calls “contextual cues” and “associative learning,” which enhances preference for the drug.
“It could mean, then, that taking drugs changes your brain in a fundamental way that makes you more sensitive to the effects of drugs in the future, including becoming addicted to them,” Crombag said.
For this reason, Wilbrecht said she would not categorize the neural development as positive or negative and emphasized that there is confusion surrounding the notion that these developments are necessarily beneficial.
“When is more learning potentially bad?” she said. “Though there is a positive correlation, I think many people would interpret that as an overall negative for the animal.”
Wilbrecht noted that the findings may simply be correlation — heightened memory skills illustrated by the mice continually hunting for the room could be solely attributed to the fact that intense arousal naturally drives learning and potential for recollection.
According the study, an investigation of the mechanisms underlying cocaine-induced spine formation might shed further light on their role in substance abuse, potentially aiding the development of therapeutic interventions for addiction.
Virgie Hoban is the lead research and ideas reporter. Contact her at [email protected].