The brain contains an intrinsic reward system that originates in the VTA and is activated by unexpected natural rewards, such as food and sex, and addictive drugs (Box 1). Within the VTA, DA neuron activity is controlled by GABA interneurons. Recently, we have shown that γ-hydroxybutyrate (GHB), an addictive club-drug, can activate DA neurons through its action on GABAB receptors [1,2]. GABAB receptors are members of a large family of G-protein-coupled receptors (GPCRs), which contain seven transmembrane domains and signal via heterotrimeric G-proteins (Gαβγ). Activation of GPCRs promotes the exchange of GTP for GDP on the Gα subunit. Activated G-proteins then dissociate into Gα-GTP and Gβγ dimers, which interact with a wide-range of effectors, including cyclases, lipases and ion channels. The Gα subunit terminates the activation by hydrolyzing GTP into GDP and reassembling the inactive heterotrimer (Gα-GDP*Gβγ).
