Now two new studies by a Yale team have identified key genes that regulate this response and show that interfering with this reaction dramatically increases a mouse's sensitivity to cocaine.
The findings may help explain why risk of drug abuse and addiction increase so dramatically when cocaine use begins during teenage years.
Researchers including those at Yale have shown that vulnerability to cocaine is much higher in adolescence, when the brain is shifting from an explosive and plastic growth phase to more settled and refined neural connections characteristic of adults.
Past studies at Yale have shown that the neurons and their synaptic connections in adolescence change shape when first exposed to cocaine through molecular pathway regulated by the gene integrin beta1, which is crucial to the development of the nervous system of vertebrates.
"This suggests that these structural changes observed are probably protective of the neurocircuitry, an effort of the neuron to protect itself when first exposed to cocaine," said Anthony Koleske, professor of molecular biophysics and biochemistry and of neurobiology and senior author of both studies.
In the latest study, Yale researchers report when they knocked out this pathway, mice needed approximately three times less cocaine to induce behavioural changes than mice with an intact pathway.
The research suggests that the relative strength of the integrin beta1 pathway among individuals may explain why some cocaine users end up addicted to the drug while others escape its worst effects, Koleske theorized.
"If you were to become totally desensitized to cocaine, there is no reason to seek the drug," he said.
The results were published in the Feb. 14 and Feb. 21 issues of the Journal of Neuroscience.