The translation of the current knowledge about the role of AMPARs in modulating synaptic plasticity to abate substance abuse would ideally produce a drug that limits AMPAR activation and reverses the long-term plasticity associated with continued cocaine seeking. This strategy is supported by the large body of rodent literature showing that AMPA antagonists inhibit the reinstatement of drug-, cue-, or stress-primed drug-seeking behavior (Backstrom and Hyytia, 2007; Cornish et al., 1999; Cornish and Kalivas, 2000; Di Ciano and Everitt, 2001; McFarland and Kalivas, 2001; McFarland et al., 2003; McFarland et al., 2004; Park et al., 2002; Ping et al., 2008; but see Bachtell et al., 2008). As a consequence, the motivation to self-administer drug as well as the propensity to relapse would be reduced. However, given the complexity of the mammalian nervous system, this may require reagents with broad-spectrum activity and indeed, several non-specific glutamatergic agents have shown much promise.
