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 DA neurons only via inhibitory interneurons located in the VTA. Enhanced activity of MSN neurons may therefore actually excite DA neurons. An appealing hypothesis is that drug-evoked synaptic plasticity reinforces the connectivity within the spiral, which would lead to the recruitment of more and more dorsal projections as drug use becomes chronic. In line with this idea are the observations that a single injection of cocaine triggers drug-evoked synaptic plasticity in VTA DA neurons that project to the medial NAc shell while several injections are require to downregulate inhibitory transmission onto DA neurons.
