al., 2004) and benzodiazepines (Tan et al., 2010) primarily target GABAergic interneurons in the VTA and decrease their activity, which leads to an indirect increase of DA neuron activity. Such disinhibition can occur because of the cell-type specific expression of the respective receptors (e.g. μ-opioid receptors are expressed on GABA- but not on DA neurons) or because GABA neurons are more sensitive to the drug than DA neurons. Benzodiazepines for example primarily silence interneurons because unitary GABA-A receptor-mediated currents in these cells are larger than in DA neurons. This observation correlates with the interneuron-specific expression of the α1 receptor subunit isoform (Tan et al., 2010). Finally, the psychostimulants cocaine, amphetamines and ecstasy, target the DA transporter (DAT), which is normally responsible for the reuptake of DA (Sulzer et al., 2005). Since midbrain DA neurons also release DA from their dendrites (Cheramy et al., 1981; Beckstead et al., 2004), DAT inhibition causes an increase of DA in the VTA as well 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.
