New findings by a Yale team of scientists may help explain why the risk of drug abuse and addiction increase significantly when cocaine use begins in adolescence.

When a teen brain is first exposed to cocaine, it launches a defensive response designed to minimize the drug’s effects. As reported in Science Daily, in two recent studies, Yale and other scientists have identified key genes that regulate this response and demonstrate that interfering with this reaction dramatically increases a mouse’s sensitivity to cocaine.

Study results were published in the Journal of Neuroscience.

Research has demonstrated that vulnerability to cocaine is much higher in the teen years, when the brain is developing. Earlier studies at Yale have shown that in adolescence, neurons and their synaptic connections change shape when first exposed to cocaine through molecular pathway regulated by the gene integrin beta1, critical to the development of the nervous system of vertebrates.

As Anthony Koleske, professor of molecular biophysics, biochemistry and neurobiology, and senior author on both papers, elaborates, “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.”

In the latest study, Yale researchers reported when the pathway was knocked out, mice needed about three times less cocaine to induce behavioral change than mice with the pathway still in place. The findings suggest that the relative strength of the integrin beta1 pathway among individuals may explain why some cocaine users become addicted to the drug while others escape its worst effects, the authors suggest.

“If you were to become totally desensitized to cocaine, there is no reason to seek the drug,” Koleske said.