CB1 Receptor Involvement in Contextual Cocaine Memory Reconsolidation

Thesis (Ph.D.), Neuroscience, Washington State UniversityEnvironmentally induced cocaine relapse is a major impediment in the treatment of substance use disorders. Re-exposure to a cocaine-associated context can trigger the retrieval of context-cocaine memories which renders these memories unstable and temporarily susceptible to modification before they are restabilized through memory reconsolidation. This process is dependent on gene transcription, de novo protein synthesis, and synaptic plasticity. Importantly, targeted interference with this process can weaken maladaptive context-drug associations and reduce the propensity for relapse. Therefore, identifying the neurobiological mechanisms underlying this process is of timely importance from a treatment perspective. Accordingly, this dissertation elucidates the involvement of cannabinoid type 1 receptor (CB1R) signaling in context-cocaine memory reconsolidation. To this end, we used an instrumental model of context-induced cocaine relapse to test the hypothesis that CB1R signaling modulates neuroadaptation during memory reconsolidation and subsequent drug-seeking behavior. Specifically, we demonstrated that CB1Rs are functionally necessary during memory reconsolidation, and we examined whether CB1R signaling is necessary for memory reconsolidation-associated molecular and synaptic adaptations in the basolateral amygdala (BLA). In subsequent experiments, we examined whether CB1R subpopulations in the BLA and dorsal hippocampus (DH) critically mediated memory reconsolidation and coinciding hypothalamic pituitary adrenal axis activation. Together, the results of this dissertation provide novel support for the CB1R as a therapeutic target for relapse prevention.Washington State University, Neuroscienc