Cocaine boosts learning and decision-making circuits in the brain - but not in a good way, a study has shown.
Using a new technique to peer into the brains of living mice, US scientists witnessed the rapid growth of structures linking memory, drug experience and behaviour. They say the findings shed new light on the way drug dependency can take over people's lives.
Within two hours of being injected with cocaine the brains of the mice started sprouting dendritic spines, twig-like structures that connect neurons. The "fast and robust" growth occurred in the frontal cortex, which controls higher functions such as planning and decision-making.
It coincided with a dramatic change in the rodents' behaviour. Given the choice of two environments, mice switched preferences to the one where they had received the cocaine shot. "This gives us a possible mechanism for how drug use fuels further drug-seeking behaviour," said Dr Linda Wilbrecht, who led the research at the University of California at San Francisco.
"It's been observed that long-term drug users show decreased function in the frontal cortex in connection with mundane cues or tasks, and increased function in response to drug-related activity or information. This research suggests how the brains of drug users might shift towards those drug-related associations."
The neurons directly affected by cocaine use had the "potential to bias decision-making", she added. To conduct the study, the scientists used a hi-tech laser scanning microscope to look directly into nerve cells through a small window in the skulls of the mice. Initially the mice were given access to two adjoining "conditioning" chambers, one smelling of cinnamon and the other vanilla, decorated with different patterns and textures.
Free to explore both compartments, individual mice settled on one they preferred. Each mouse was then placed in the chamber they had rejected after being injected with cocaine. From then on, they gravitated to the compartment associated with the drug.
"When given the choice, most of the mice preferred to explore the side where they had the cocaine, which indicated that they were looking for more cocaine," said Dr Wilbrecht. "Their change in preference for the cocaine side correlated with gains in new persistent spines that appeared on the day they experienced cocaine.
"The animals that showed the highest quantity of robust dendritic spines.. showed the greatest change in preference towards the chamber where they received the cocaine. This suggests that the new spines might be material for the association that these mice have learned to make between the chamber and the drug."
The findings are published in the latest edition of the journal Nature Neuroscience. Previous post-mortem studies of human brains have shown changes in dendritic spine density after weeks of repeated cocaine use.