Steven E. Hyman* but not DA reuptake, produce neither significant reinforcement in animal models nor euphoria in humans. Laboratory of Molecular and Developmental Neuroscience Moreover, antidepressants do not produce dependence in humans even with very long-term use. In addition, Massachusetts General Hospital Harvard Medical School lesioning of DA terminals within the NAc or full pharmacological blockade of DA receptors inhibits cocaine or Boston, Massachusetts 02114 amphetamine self-administration (reviewed by Self and Nestler, 1995). It is also significant that mice lacking the Addiction to the psychostimulant drugs, of which co-DAT are entirely insensitive to the locomotor stimulant caine and the amphetamine derivatives are the most effects of cocaine or amphetamine (Giros et al., 1996). important, is one of the foremost public health problems The precise contributions of different postsynaptic DA in the United States. Cocaine and amphetamine share receptors to reinforcement have yet to be fully estabtwo critical properties with other addictive drugs: they lished because of the lack of adequately selective antagare reinforcing when administered acutely (ie, drug use onists directed against the five known DA receptors. entails repeated drug use) and produce compulsive use Studies of drug self-administration in mice with disrupif administered chronically with adequate dose and fretions in the genes encoding each of the different DA quency. receptorsaswellastheDATmayalsoproveinformative;