as in the NAc and PFC. Important mechanistic differences exist between the individual members of this class. Cocaine directly inhibits the DAT, while amphetamines are transporter substrates that are taken up into the cell to enhance non-vesicular release of DA. Psychostimulants have in common that they decrease the firing rate of DA neurons through D2 receptor mediated autoinhibition (Groves et al., 1975) (Chen and Reith, 1994). The Gi/o coupled D2 receptors hyperpolarize DA neurons by activating GIRK/Kir3 channels. Because the block of DA reuptake exceeds the consequences of reducing DA cell firing frequency there is nevertheless a net increase of ambient DA.
