Cocaine triggers rapid growth in new brain structures linked to memory and learning, but only in a way that encourages drug-seeking behavior, researchers from the Ernest Gallo Clinic and Research Center at UC San Francisco reported in the journal Nature Neuroscience.
The scientists believe their study, which was carried out on laboratory mice, suggests a novel way in which cocaine users select environments associated with the drug.
Principal investigator, Linda Wilbrecht, PhD, and colleagues used a special microscope to look directly into the neurons (nerve cells) inside the brains of living mice.
They found considerable increases in the density of dendritic spines in the frontal cortex (frontal lobe) within two hours of administering cocaine to the mice. Dendritic spines are structures that bear the synapses required for signaling; they are key to how messages pass from one nerve cell to another. Dendritic spines store neuronal information.
When mice were given saline solution, the scientists found no such increase in dendritic spine density.
Dr. Wilbrecht added that they also detected a relationship between increased dendritic spine density and drug-associated learning. The mice with the most new spines sought out enclosures where they received cocaine much more keenly than the other mice.
Dr. Wilbrecht said:
"This gives us a possible mechanism for how drug use fuels further drug-seeking behavior. 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 toward those drug-related associations."
Cocaine might be a super-learning stimulus
The frontal cortex, the blue part of the image, controls long-term planning, decision making, high reasoning, discipline and other behaviors.
There is a baseline level of creation of new spines in anticipation of or response to day-to-day learning in all living brains, the authors explained.
The frontal cortex controls our long-term planning, as well as decision-making and other behaviors that involve discipline and high reasoning. Wilbrecht calls the frontal cortex the "steering wheel" of the brain.
The frontal cortex brain cells which are affected by cocaine use have the potential to bias decision making, Wilbrecht said.
The researchers say their findings may help advance research into human addiction "by helping us identify what is going awry in the frontal cortexes of drug-addicted humans, and by explaining how drug-related cues come to dominate the brain's decision-making processes."
In this study, the scientists divided the mice into two groups:
- The cocaine group - mice were given cocaine injections.
- The saline group - mice were given saline injections.
They then observed the mice's brain cells using a 2photon laser-scanning microscope.
Accelerated dendritic spine growth occurs soon after taking cocaine
It did not take long for the cocaine group mice to grow more new dendritic spines than those in the saline group. The team was surprised to find that this occurred after the mice received their first dose of cocaine.
In a separate experiment, the mice in either group were observed before and two hours after being given cocaine or saline. Those in the cocaine group were developing new dendritic spines within two hours of being given the drug.
By the next morning the mice in the cocaine group had created nearly four times more connections among nerve cells compared to those in the saline group.In another experiment the mice were given cocaine in one chamber and saline in another. The procedures were identical but the chambers were different visually, in texture and smell, so that the mice could distinguish one from the other.
Their aim was to observe the mice in either group to see whether they preferred one chamber to go to.
"The animals that showed the highest quantity of robust dendritic spines - the spines with the greatest likelihood of developing into synapses - showed the greatest change in preference toward 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 team said that without the 2-photon laser scanning microscope there would have been no live brain imaging. The 2-photon laser scanning microscope was developed in 2002.
Wilbrecht recalled "I grew up at the time of the famous public service campaign that showed a pan of frying eggs with the message, 'this is your brain on drugs.' Now, with this microscope, we can actually say, 'this is a brain cell on drugs.'"
Cocaine vaccine trial shows promise
Researchers at the Weill Cornell Medical College reported in the journal Neuropsychopharmacology that an experimental anti-cocaine vaccine was successfully tested on primates, suggesting that human trials may not be far off.
The vaccine stops cocaine from getting to the brain and causing a dopamine-induced high.
Principal investigator, Dr. Ronald G. Crystal, said "The vaccine eats up the cocaine in the blood like a little Pac-man before it can reach the brain. We believe this strategy is a win-win for those individuals, among the estimated 1.4 million cocaine users in the United States, who are committed to breaking their addiction to the drug," he says. "Even if a person who receives the anti-cocaine vaccine falls off the wagon, cocaine will have no effect."