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 field potentials and generated by presumptive prefrontal-NAc synapses, was modestly enhanced (Yao et al., 2004). Finally, during withdrawal from cocaine self-administration, both LTP and LTD at prefrontal-NAc synapses in vivo were impaired (Moussawi et al., 2009). The difference in these results may reflect that different sets of inputs were in fact stimulated as well as the differences in the drug administration protocols. A significant limitation of using in vivo preparations is the technical difficulty of recording synaptic responses from individual cells. Instead, extracellular field potentials are normally recorded, changes in which are difficult to interpret since the potentials are generated both by synaptic responses and voltage-dependent conductances. A further limitation of in vivo extracellular recordings is the difficulty in performing assays of basal synaptic properties in a manner that permits cross preparation comparisons. Ideally, it would be valuable to combine the advantages of both in vivo and ex vivo approaches while minimizing their limitations. An obvious approach to accomplish this
