These data indicate a role for RasGRF2 in cocaine SA in mice that is ERK-dependent, and suggest a differential effect of global versus site-specific RasGRF2 inhibition.<b>SIGNIFICANCE STATEMENT</b> Exposure to drugs of abuse activates a variety of intracellular pathways, and following repeated exposure, persistent changes in these pathways contribute to drug dependence.
Together, these combined animal and human data indicate a role for RASGRF2 in the regulation of mesolimbic dopamine neuron activity, reward response, and alcohol use and abuse.