The following all holds for selegiline, except without any concern for 'reinforcement' of the abuse variety. "We have documented that in the human brain therapeutic doses of methylphenidate block more than 50% of the dopamine transporters and significantly enhance extracellular DA, an effect that appears to be modulated by the rate of DA release. Thus, we postulate that methylphenidate's therapeutic effects are in part due to amplification of DA signals, that variability in responses is in part due to differences in DA tone and that methylphenidate's effects are context dependent. Methylphenidate-induced increases in DA are also associated with its reinforcing effects but only when this occurs rapidly, as with intravenous administration. Moreover, abuse of methylphenidate is constrained by its long half-life, which we postulate limits the frequency at which it can be administered."