Nicotine causes changes in gene regulation that enhance the brain’s subsequent response to cocaine. The finding, in mice, provides the first clear evidence for a molecular mechanism supporting the idea of ‘gateway drugs’.
Epidemiologist Denise Kandel at Columbia University, New York, reported back in 1975 that drug-using adolescents had tended to start with cigarettes, which contain the addictive substance nicotine, and alcohol before progressing to more illicit substances such as cocaine. The idea that smoking and alcohol act as a gateway, making teenagers more likely to experiment with other drugs, has proved controversial ever since.
In a study published this week in Science Translational Medicine, Kandel and her team now show that, in mice at least, nicotine causes epigenetic changes — long-lasting changes in the control of gene expression — that subsequently boost the response to cocaine. The reverse didn’t hold, however. Cocaine had no effect on nicotine-induced behaviour.
To investigate, the researchers plied mice with nicotine, followed seven days later by cocaine. What they found was striking. Compared with mice on cocaine who had not previously received nicotine, the animals were 98% more active and 78% more likely to return to areas previously associated with the cocaine.
The results can help guide epidemiological studies to tease apart the relationship between cocaine use and smoking, Kandel says, including the effects of the age that someone starts smoking, how much they smoke, and what other drugs they take.
Levine and Eric Kandel now hope to determine whether alcohol and marijuana similarly prime the response to illicit drugs or have a different effect. “Is there a common gateway mechanism or a family of gateway mechanisms?” says Kandel.
Kandel, D. (1975). Stages in adolescent involvement in drug use Science, 190 (4217), 912-914 DOI: 10.1126/science.1188374
Amir Levine1,, YanYou Huang1,, Bettina Drisaldi1,, Edmund A. Griffin Jr., Daniela D. Pollak, Shiqin Xu1, Deqi Yin1, Christine Schaffran, & Eric R. Kandel (2011). Molecular Mechanism for a Gateway Drug: Epigenetic Changes Initiated by Nicotine Prime Gene Expression by Cocaine Science Translational Medicine, 3 (107), 107-109 : 10.1126/scitranslmed.3003062