COCAINE REWARD MODELS - CONDITIONED PLACE PREFERENCE CAN BE ESTABLISHED IN DOPAMINE-TRANSPORTER AND IN SEROTONIN-TRANSPORTER KNOCKOUT MICE

Cocaine and methylphenidate block uptake by neuronal plasma membrane t ransporters for dopamine, serotonin, and norepinephrine. Cocaine also blocks voltage-gated sodium channels, a property not shared by methylp henidate. Several lines of evidence have suggested that cocaine blocka de of the dopamine transporter (DAT), perhaps with additional contribu tions from serotonin transporter (5-HTT) recognition, was key to its r ewarding actions. We now report that knockout mice without DAT and mic e without 5-HTT establish cocaine-conditioned place preferences. Each strain displays cocaine-conditioned place preference in this major mou se model for assessing drug reward, while methylphenidate-conditioned place preference is also maintained in DAT knockout mice. These result s have substantial implications for understanding cocaine actions and for strategies to produce anticocaine medications.