It will also be important to understand how the different forms of drug-evoked plasticity in the mesocorticolimbic system relate to each other. Anatomical analysis in rodents and non-human primates suggest that the midbrain and striatal components of the mesocorticolimbic DA system are connected in a spiraling manner (Haber et al., 2000; Ikemoto, 2007). DA neurons of the medial VTA project to the medial shell, from where MSNs back-project to more lateral parts of the VTA. This backprojection most likely involves a relay via an interneuron in the VTA (Maeda and Mogenson, 1981; Xia et al., 2010). These DA neurons then project to the NAc core, from where MSNs backproject to even more lateral VTA, and, after several additional loops, the circuit reaches the substantia nigra (SNc) which projects to the dorsal striatum. The ascending projections are in general dopaminergic along with a glutamatergic component for a subset of neurons that co-release both transmitters (Dobi et al., 2010). NAc MSNs that send GABAergic projections to the VTA are likely to be direct pathway or D1 expressing neurons, but most MSNs reach
