The results summarized thus far emphasize the importance of defining the cell type in which drug-induced adaptations have occurred. As mentioned above, of equal importance will be defining the source of the synapses being studied. Currently, using ex vivo approaches that involve preparing acute brain slices from animals that have had drug experience; it is very difficult to know definitively which sets of inputs are being activated. For the NAc, these arise primarily from the prefrontal cortex, subiculum or amygdala. Furthermore, with standard techniques, it is impossible to prevent the activation of GABAergic, dopaminergic or other modulatory inputs within the slice. The potential importance of distinguishing the different NAc afferents is exemplified by in vivo experiments during which it is possible to activate specific sets of inputs independently. For example, at hippocampal-NAc synapses, LTP recorded using extracellular field potentials was reported to be impaired 2–3 weeks following repetitive non-contingent cocaine administration whereas LTP at prefrontal-NAc synapses was unaffected (Goto and Grace, 2005). On the other hand, in acute slices prepared two weeks after repetitive cocaine administration, LTP, also assayed using
