Site-specific inhibition of signaling targets

The current studies employed systemically administered modulators of various
signaling molecules and showed in some instances a similar effect on Fix-C and Esc-C
memory while in other cases differential effects. While the use of pharmacological tools
could be the gold standard for the treatment of human addicts, in order to better
understand the mechanisms associated with drug-associated behavior, it is necessary to
elucidate the contribution of specific brain regions to these effects. As such, brain regionspecific
injection of modulators of signaling molecules may aid in this endeavor. This
will reduce the ‘noise’ associated with systemic administration since there is always the
potential for test drugs to have off-target effects that may influence behavior.
Additionally, future studies using region-specific and conditional knockout (KO) models
of specific signaling targets will be of great value in specifying the roles of anatomical
substrates for cocaine-associated memory. For instance, conditional and inducible
manipulation of specific signaling molecules will minimize the potential for
compensatory mechanisms that could functionally substitute for the inhibited molecule.


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