To answer this question, studies have compared the ability of stimulant drugs [methylphenidate (MPH) and amphetamine (AMPH)] to increase DA in the striatum of addicted versus nonaddicted subjects. Similar to cocaine, MPH increases DA by blocking DA transporters, whereas AMPH (similar to methamphetamine) increases DA by releasing it from the terminal using the DA transporter as carrier. Intravenous injection of these stimulant drugs is highly rewarding, and cocaine abusers report the effects to be similar to those of intravenous cocaine. Cocaine-addicted but detoxified subjects show marked attenuation of DA increases in the striatum induced by MPH or AMPH (at least 50% lower) and an attenuation of their self-reported “high,” when compared with non-drug-abusing controls (20, 28). Moreover, a more recent study provides the first comparison of responses to intravenous MPH in actively using cocaine abusers and showed that in these subjects MPH effects on striatal DA could not be distinguished from placebo (29). A comparison with the responses of the non-drug-abusing controls revealed the striatal DA changes in the cocaine abusers were 80% lower than in controls (Figure 2). Marked
