Models of dopamine function based on the bidirectional neuromodulation of afferents (40, 95) were tested by determining whether cortical ablation would affect the excitatory and inhibitory effects of amphetamine (AMPH) on striatal neurons in freely moving rats. By minimizing pre-and post-AMPH behavioral differences, behavioral clamping revealed that cortical ablation blocked the capacity of AMPH to produce a net excitation of striatal neurons that had shown AMPH-induced excitations under non-clamping conditions. Cortical ablation did not affect AMPH-induced neuronal inhibitions under behavioral clamping conditions. These results suggest that AMPH, possibly by enhancing dopaminergic neuromodulation, facilities or inhibits the activity of neurons that respectively receive substantial or little cortical input. Thus, the findings support models that assign dopamine the capacity to increase the gain of neuronal information processing. Basic research relevant to these models is reviewed and potential clinical implications are discussed.