The nAChR system is part of the brain reward circuitry that mediates the rewarding effect of amphetamine drugs by facilitating the release of dopamine54,55, and plays a key role in drug self-administration56. Repeated exposure to methamphetamine inhibited the corticostriatal release of dopamine similar to the classic nAChR agonist nicotine, an effect reversed by methamphetamine re-administration57. The CHRNA3-CHRNA5-CHRNB4 gene cluster of nAChRs has been associated consistently with nicotine dependence17 and multiple smoking behaviors58,59.
