Site-specific inhibition of signaling targets

The current studies employed systemically administered modulators of varioussignaling molecules and showed in some instances a similar effect on Fix-C and Esc-Cmemory while in other cases differential effects. While the use of pharmacological toolscould be the gold standard for the treatment of human addicts, in order to betterunderstand the mechanisms associated with drug-associated behavior, it is necessary toelucidate the contribution of specific brain regions to these effects. As such, brain regionspecificinjection of modulators of signaling molecules may aid in this endeavor. Thiswill reduce the ‘ noise’ associated with systemic administration since there is always thepotential for test drugs to have off-target effects that may influence behavior. Additionally, future studies using region-specific and conditional knockout (KO) modelsof specific signaling targets will be of great value in specifying the roles of anatomicalsubstrates for cocaine-associated memory.

For instance, conditional and induciblemanipulation of specific signaling molecules will minimize the potential forcompensatory mechanisms that could functionally substitute for the inhibited molecule.