Neuron 59, 621–633 (2008)

Repeated exposure to cocaine increases the density of connections among the nerve cells in a brain region that is central to motivation and reward. The change seems to stymie long-lasting behaviours associated with chronic drug use rather than promote them, as scientists had previously thought.

Working with mice, Christopher Cowan at the University of Texas Southwestern Medical Center in Dallas and his colleagues have found that cocaine suppresses the protein MEF2, encouraging medium-sized spiny neurons in the nucleus accumbens to form more links. Artificially upping the levels of MEF2 blocked this process, as expected, but surprisingly caused mice to behave as though their sensitivity to cocaine had increased.

The researchers propose that MEF2 suppression and the consequent increase in neuronal connections attenuate the harmful effects of long-term cocaine use.