Just a couple of doses of cocaine can change the composition of the part of the brain associated with memory-based decision making, according to a team of researchers at the Ernest Gallo Clinic and Research Center at UC San Francisco.
Almost immediately, mice that were administered cocaine grew far more new dendritic spines, which can form synapses and create new connections, than did mice that just got saline, according to a study published online Sunday in Nature Neuroscience.
"The fact that cocaine appears to rewire executive centers with one dose is pretty shocking," said Linda Wilbrecht, a UC Berkeley neurology researcher affiliated with the center. "It isn't that they came up over night, while the mouse was sleeping. They actually came up within two hours of the cocaine experience."
Subsequent experiments suggested that those new spines correlated with what appeared to be addict behavior: Given a choice, mice with those new neuron spines headed back to the cocaine lounge. In scientific terms, they exhibited a "conditioned place preference" for the chamber where they got the cocaine, over the one where they got saline.
"The ones that developed the biggest change in preference for the cocaine side were also the ones that grew the most spines," said Wilbrecht.
That result suggests that the new cell population may have formed associative memories driving behavioral decisions, according to the study.
The research team, which also included faculty from UC San Francisco, used genetically altered mice with clear plates inserted in their skulls, enabling the researchers to view new cells lighting up under a two-photon microscope.
Although changes in nerve formation and structure in the cerebral cortex after cocaine use have been demonstrated before, seeing them in a "live" situation in this type of microscopy was novel, said University of Sussex neuroscientist Hans Crombag, who has done similar research. "This is probably the best and most state of the art demonstration" of those changes, Crombag said.
A mouse lacks the complex brain structure found in Homo sapiens, but it shares enough of our neurobiological characteristics to be a widespread and useful model in experiments. And some of the results of the Gallo study appear to mirror imaging done on the brains of human addicts, said Wilbrecht.
Still, "it is just a correlation," Wilbrecht said. "There may be intervening factors like arousal" that modulate the apparent behavior.
Further study could lead toward new therapies aimed at re-conditioning or interrupting the addictive circuitry and altering behavior, the authors said.
The research team is interested next in seeing what happens when mice are given the opportunity to administer the drug themselves, and examining how effects might be different in the brains of mice of varied ages, across genders.