Jessica Loweth, Rosalind Franklin University of Medicine and Science
A major challenge for treating cocaine addiction is the propensity for abstinent users to relapse. Two important triggers for relapse are cues associated with prior drug use and stressful life events. However, the mechanisms underlying cue- and stress-induced relapse are not well-understood. To study the synaptic changes that maintain vulnerability to relapse even after long periods of abstinence, we use the ‘incubation of craving’ model, in which cue-induced craving in rats progressively intensifies (“incubates”) during the first months of withdrawal from extended-access self-administration of cocaine or other addictive drugs. Incubation provides an animal model for a common human scenario in which withdrawal is imposed by incarceration or hospitalization and has recently been demonstrated in humans during withdrawal from alcohol, cocaine, nicotine and methamphetamine. My seminar will focus on recent animal studies we have conducted using the incubation model in which we have identified a glutamatergic receptor—metabotropic glutamate receptor 1 (mGluR1) — as a potential therapeutic target to reduce cue-induce craving in abstinent cocaine addicts. I will also discuss recent studies that will provide the groundwork for my future studies as an independent investigator in which I am investigating chronic stress-induced changes in relapse vulnerability in the incubation model. My data indicate that chronic stress exposure during early withdrawal from cocaine self-administration enhances the initial rate of incubation of cue-induced cocaine craving, resulting in increased vulnerability to cue-induced relapse during this period. These studies will lay the groundwork for future studies which will assess the synergistic effects of cocaine and chronic stress exposure during withdrawal on cellular and behavioral measures and, using a stress resilience model, identify neuroadaptations that can reverse such effects. Together, these studies will ultimately bring us closer to developing effective pharmacotherapies to reduce craving and prevent relapse in abstinent cocaine addicts.