UC Santa Barbara

Incubation of craving is the phenomenon in which craving intensifies over the course of abstinence. Although understanding craving may be key in understanding why relapse occurs, not much is known about craving, especially the underlying mechanisms that occur in the brain. Clinical and preclinical models have recently implicated the ventromedial prefrontal cortex as one of the key regions in this phenomenon. In order to further characterize this region’s role in incubation, a variety of behavioral, pharmacological, and molecular techniques are used to examine how withdrawal from long access cocaine self-administration directly affects the glutamatergic system. The series of experiments detailed in this dissertation aim to: (1) characterize extracellular glutamate fluctuations in the vmPFC during the incubation of cocaine-seeking, (2) characterize metabotropic glutamate receptor (mGlu) 2/3 changes during both short term and long term withdrawal, and (3) to determine the functional relevance of endogenous glutamate in the two subregions of the vmPFC. Taken together, these experiments suggest that although there seem to be no changes in mGlu2/3 at either point of withdrawal, glutamate in the prelimbic cortex of the vmPFC is functionally relevant in the incubation of cocaine seeking. Together, these results suggest pharmacotherapeutic strategies geared toward damping excitatory glutamate drive within corticofugal projections from the prelimbic cortex may be effective to prevent incubated cue-induced craving during protracted abstinence.