Gene involved in response to cocaine identified

Washington – Neuroscience researchers including an Indian origin scientist have identified a gene in mice that appears to underlie the intensity of the response to cocaine.

The UT Southwestern Medical Center researchers suspect that the newly identified gene, Cyfip2, determines how mammals respond to cocaine, although it is too soon to tell what the indications are for humans or for addiction.

The findings evolved from examining the genetic differences between two substrains of the standard C57BL/6 mouse strain: a “J” strain from the Jackson Laboratory (C57BL/6J) and an “N” strain from the National Institutes of Health (C57BL/6N). Researchers compared the two strains of mice and used their differential responses to cocaine to identify the causative gene.

“We found that the ‘N’ strain has accumulated mutations over time, one of which has a very strong effect on cocaine response,” Dr. Joseph Takahashi, senior author of the study, said. “We propose that CYFIP2 – the protein produced by the Cyfip2 gene – is a key regulator of cocaine response in mammals.”

The Takahashi laboratory has identified about 100 genetic differences that affect protein sequences between the two mouse strains, meaning that there are many genetic differences whose effects are not yet known, he added.

Dr. Takahashi said they identified this gene by first using a forward genetics strategy to search for differences in traits between the two mouse strains. We found a difference in cocaine response between them, with the C57BL/6N strain showing a reduced behavioral response.

They then carried out genetic mapping and whole genome sequencing, which allowed us to pinpoint the Cyfip2 gene as the causative one in a rapid and unambiguous way.

The study is published in journal Science.