signaling that is often observed following repeated exposure to cocaine would represent a very effective way to prevent relapse. Indeed, other agents that weakly elevate activity of other glutamate receptors such as NMDARs, have shown some efficacy to reduce cocaine reinforcement in pre-clinical models (Bowers et al., 2007) Phase I clinical trials with Campral (acamprosate), a non-specific glutamate receptor modulator, have been completed (Identifier: NCT00385268). Among several other plausible mechanisms of action, acamprosate might also block the AMPA receptor pore, given the ability to modulate polyamine binding to the NMDA receptor (Kast and Altschuler 2007). Similarly, agents such as Provigil (modafinil), Mucomyst/Acetadote (N-acetyl cysteine), and Rocephin (ceftriaxone) have shown efficacy to reduce cocaine seeking (Baker et al., 2003; Knackstedt et al., 2009; Madayag et al., 2007; Martínez-Raga et al., 2008; Moran et al., 2005). N-acetylcysteine elevates glutamate levels affecting both ionotropic and metabotropic glutamate receptors, and is currently being studied as a therapeutic agent against substance abuse (Identifiers: NCT00136825; NCT00218491). A thorough discussion of these compounds is beyond the scope of this review, but recent reviews have discussed the therapeutic potential of the most promising agents (Uys and LaLumiere, 2008; Kalivas, 2009).
