I will speak on two separate projects in our lab. First, we have uncovered the molecular mechanism by which administration of the Zeta Inhibitory Peptide (ZIP) causes memory loss. While it was previously believed that ZIP administration perturbs memory stability through disruption of constitutive kinase activity, recent studies have cast doubt on this hypothesis. However, ZIP’s effects on memory stability are robust, raising the question of what the actual mechanism is by which ZIP exerts its function. We have identified the basic molecular and pathways engaged by ZIP, and use this information to identify an inhibitor that, together with ZIP, enables bidirectional modulation of synaptic plasticity. Second, we are exploring the biological factors that influence the behavioral response to the administration of drugs of abuse. Some individuals that take drugs of abuse are susceptible to developing dependence, while others are resilient. The fundamental source of this variation is not understood. We will discuss our work implicating circuit- and molecular-level changes in the globus pallidus that facilitate individual differences in response to cocaine administration, and share the identification of a novel small molecule compound, isolated from rosemary, that blunts drug reward and volitional intake.